cord-020087-gs0pc6ee	2010	Myristoylation of the small envelope protein of porcine reproductive and respiratory syndrome virus is non-essential for virus infectivity but promotes its growth 294 Porcine reproductive and respiratory syndrome virus (PRRSV) could be sensed by professional beta interferon-producing Hikichi (Japan) The 126-and/or 183-kDa replicases or their coding regions are responsible both for inefficient local and for systemic movements of Paprika mild mottle virus Japanese strain in tomato plants USA) Genetic control of host resistance to porcine reproductive and respiratory syndrome virus (PRRSV) infection Porcine reproductive and respiratory syndrome virus (PRRSV) in serum and oral fluid samples from individual boars: Will oral fluid replace serum for PRRSV surveillance USA) Use of a production region model to assess the efficacy of various air filtration systems for preventing airborne transmission of porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae: Results from a 2-year study 177 Morrison (USA) Control and elimination of porcine reproductive and respiratory syndrome virus 185 Cumulative Author Index for
cord-020097-eh5deunk	2006	Modulation of PKR activity in cells infected by bovine viral diarrhea virus Complete genome analysis of RFLP 184 isolates of porcine reproductive and respiratory syndrome virus Phylogenetic analysis of the gag region encoding the matrix protein of small ruminant lentiviruses: Comparative analysis and molecular epidemiological applications TATAbinding protein and TBP-associated factors during herpes simplex virus type 1 infection: Localization at viral DNA replication sites Inhibition of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infectivity by peptides analogous to the viral spike protein Efficient inhibition of hepatitis B virus replication by small interfering RNAs targeted to the viral X gene in mice Preparation and characterization of a novel monoclonal antibody specific to severe acute respiratory syndrome-coronavirus nucleocapsid protein A deletion and point mutation study of the human papillomavirus type 16 major capsid gene Sequencing and comparative analysis of a pig bovine viral diarrhea virus genome Antigenic structure analysis of glycosylated protein 3 of porcine reproductive and respiratory syndrome virus
cord-020101-5rib7pe8	2008	Cauliflower mosaic virus gene VI product N-terminus contains regions involved in resistance-breakage, self-association and interactions with movement protein Intrahost evolution of envelope glycoprotein and OrfA sequences after experimental infection of cats with a molecular clone and a biological isolate of feline immunodeficiency virus DC-SIGN enhances infection of cells with glycosylated West Nile virus in vitro and virus replication in human dendritic cells induces production of Increase in proto-oncogene mRNA transcript levels in bovine lymphoid cells infected with a cytopathic type 2 bovine viral diarrhea virus Complete genome sequence analysis of dengue virus type 2 isolated in Modulation of hepatitis B virus replication by expression of polymerasesurface fusion protein through splicing: Implications for viral persistence Induction of apoptosis in Vero cells by Newcastle disease virus requires viral replication, de-novo protein synthesis and caspase activation Mechanisms of inhibition of HIV replication by non-nucleoside reverse transcriptase inhibitors
cord-252048-ftbjsoup	2011	The full-length genomes of 11 infectious bronchitis virus (IBV) field isolates from three different types of the virus; Massachusetts (Mass), Connecticut (Conn) and California (CAL) isolated over a 41, 25 and 8 year period respectively, were sequenced and analyzed to determine the mutation rates and level of polymorphisms across the genome. The genetic data also identified a recombinant IBV isolate with 7 breakpoints distributed across the entire genome suggesting that viruses within the same serotype can have a high degree of genetic variability outside of the spike gene. The objective of this study was to determine the levels of polymorphism across the entire genome of IBV isolates with similar spike genes and to examine the mutation rates for viruses with and without vaccine selection pressure.
cord-255857-y9wjp0aj	2001	Two full-length porcine reproductive and respiratory syndrome virus (PRRSV) genomes, strain VR-2332 and its cell culture passaged descendent RespPRRS vaccine strain, were compared and analyzed in order to identify possible sites of attenuation. However, the cluster of amino acid mutations located near the carboxyl terminal end suggests that the replicase region was altered during passage to result in a more fit virus for replication in cell culture, as evidenced by the in vitro one-step growth curve comparison shown in Fig. 4 . Sequence analysis of strains VR-2332 and RespPRRS indicated that there were 15 nucleotide changes in this region, and all but one of which resulted in amino acid alterations. Attenuation can result from changes in many areas of viral genomes and the 41 nucleotide mutations described include alterations in several key PRRSV regions.
cord-256343-dtfw8o4g	2013	Neighbor-joining distance tree for the relative synonymous codon usage (RSCU) for the Avian coronavirus spike (S), nucleocapsid (N), non-structural protein 2 (NSP2) and papain-like protease (PL pro ) genes and the Gallus gallus beta-actin, lung surfactant protein A (SFTPA1, gray background), intestinal cholecystokinin (CCK), oviduct ovomucin alpha subunit (OSA) and kidney vitamin D receptor genes. The mean number of amino acid residues in the sequences used for this study from the Avian coronavirus spike (S), nucleocapsid (N), non-structural protein 2 (NSP2) and papain-like protease (PL pro ) genes coded by a preferred codon and the preferred codon for each aa in the Gallus gallus beta-actin (B-act), lung surfactant protein A (SFTPA1), intestinal cholecystokinin (CCK), oviduct ovomucin alpha subunit (Ovo) and kidney vitamin D receptor (ViTD rec) genes.
cord-257487-xanqvdhn	2012	Knockdown of the cellular FK506-binding proteins FKBP1A and FKBP1B in CaCo2 cells prevented replication of HCoV-NL63, suggesting the requirement of these members of the immunophilin family for virus growth. Here we demonstrate that the drug FK506 (Tacrolimus) inhibited strongly the growth of human coronaviruses SARS-CoV, HCoV-NL63 and HCoV-229E at low, non-cytotoxic concentrations in cell culture. Knockdown of the cellular FK506binding proteins FKBP1A and FKBP1B in CaCo2 cells prevented replication of HCoV-NL63, suggesting the requirement of these members of the immunophilin family for virus growth. To examine whether FK506 exerts an inhibitory activity on other human coronaviruses, CaCo2 cells were infected with HCoV-NL63 at MOI = 0.004 (Herzog et al., 2008) in the presence of increasing inhibitor concentrations. In order to examine whether the cellular FK506-binding proteins FKBP1A and FKBP1B are required for virus replication, CaCo2 knockdown cell lines were established using lentiviral expression of shRNA (Sirion GmbH, Martinsried, Germany).
cord-257715-pbcr81qm	2009	Thus, there have been a few reports where indirect ELISA using partially purified BToV or BEV particles were used for torovirus serodiagnosis, but purification procedures are not affordable by all laboratories and, in addition, this assay would also provide low sensitivity for detection of antibodies to human and porcine toroviruses (Brown et al., 1987) . Lack of cross-reactivity between PToV and antibodies to other related viruses infecting pigs was confirmed by ELISA, Western blot and virus neutralization tests using ␣PRRSV, ␣PRCV, and ␣BRES serum samples, purified PToV N protein or BEV particles as toroviral antigens, and purified PRRSV and TGEV virions as related viruses (data not shown). In order to evaluate the potential use of the PToV-N protein as antigen for diagnostic ELISA to detect antibodies against porcine torovirus, 45 serum samples were collected from three Spanish farms located in Galicia, Navarra and Aragon and were analyzed by ELISA, virus neutralization assay and/or Western blot. Recombinant PToV-BRES-N protein was used to develop an ELISA assay to detect antibodies against torovirus in swine serum samples.
cord-258294-ny3xrjzc	2020	Compared with nonvaccinated pigs, conventional weaned pigs given the inactivated vaccine developed a potent humoral immune response and showed no clinical signs or viral shedding after challenge, indicating a potent protective effect of the vaccine against PDCoV infection. Piglets in the infection group and mock control group were separately inoculated with 3 ml of MEM containing 1.0×10 4 TCID50 of the cell culture-adapted PDCoV strain CH/XJYN/2016-P6. To determine a standardized and validated dose for the subsequent pig challenge experiments, the median pig diarrhea dose (PDD50) of P6 of the cell culture-adapted PDCoV strain, CH/XJYN/2016, was determined by using conventional weaned pigs as described in our previous study (Zhang et al., 2019a) . Therefore, the infectious titer (PDD50) of PDCoV in two-month-old conventional pigs and the protection efficacity of an inactivated vaccine based on the cell-adapted strain CH/XJYN/2016 were determined for the first time in the present study.
cord-258546-1tf5ggfo	2016	Since outbreaks of porcine epidemic diarrhea virus (PEDV) in the United States in 2013, explosive outbreaks of PED in South Korea have infected all age groups of pigs in 2014–2015 year. PED outbreaks re-occurred in Korea in 2013, however, it was demonstrated that the emerging PEDVs were not variants of old Korean isolates or attenuated vaccine strains (Chung et al., 2015) . This study tested whether PEDV isolated recently was crossed neutralized by serum of pigs which were vaccinated with Korean PED oral vaccine (Attenuated DR13 strain, Green Cross Veterinary Product Co., Ltd., Yong-In, Korea). Comparative genome analysis and molecular epidemiology of the reemerging porcine epidemic diarrhea virus strains isolated in Korea ISolation of porcine epidemic diarrhea virus during outbreaks in South Korea Isolation of porcine epidemic diarrhea virus (PEDV) in Korea Heterogeneity in spike protein genes of porcine epidemic diarrhea viruses isolated in Korea
cord-259044-mubjm22l	2019	The study indicated the inhibitory activity of Sambucus FormosanaNakai extract and its phenolic acid constituents on HCoV-NL63 induced cytopathic effect, virus yield, and the early stage of HCoV-NL63 replication in concentration-dependent and cell-type independent manners. LLC-MK2 cells (3 × 10 4 cells/well) were cultured in the 96-well plates overnight, quintuplicate treated with Sambucus Formosana Nakai stem ethanol extract or its phenolic acid constituents (caffeic acid, chlorogenic acid, coumaric acid, ferulic acid, and gallic acid) for 2 days, and then incubated with 0.5 mg/ml 3-(4,5-Dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) for additional 4 h. For minimizing the antiviral effect of indicated agents in the cells, 100 μl (near 200 pfu HCoV-NL63) of the 10000-fold dilution from the mixtures of virus and the extract or phenolic acids was added to the MK2 cell monolayer in the 6-well plate to determining the residual viral infectivity using the plaque assay described above. To examine the antiviral mechanism of caffeic acid and chlorogenic acid against HCoV-NL63, the assays of plaque formation, virucidal activity and virus attachment were subsequently performed (Fig. 5 , Table 1 ).
cord-259671-7de21oaq	2014	Overall, the conservation pattern identified for 5′ and 3′-terminal RNA structural elements in the genomes of alphaand betacoronaviruses is in agreement with the widely used replicase polyprotein-based classification of the Coronavirinae, suggesting co-evolution of the coronavirus replication machinery with cognate cis-acting RNA elements. Other internal cis-acting elements include specific RNA signals required for genome packing, which have been characterized in a small number of coronaviruses Escors et al., 2003; Morales et al., 2013; Penzes et al., 1994) , and a complex RNA pseudoknot structure located in the ORF1a-ORF1b overlap region that mediates a (−1) ribosomal frameshift event and thus controls the expression of the second large ORF on the coronavirus genome RNA (ORF1b) (Brierley et al., 1987 (Brierley et al., , 1989 de Haan et al., 2002; Namy et al., 2006) .
cord-259935-xyo2pe4g	2017	To examine the association of SARS-CoV PLpro-induced TGF-β1 production with the collagen up-regulation, A549 lung epithelial cells transiently transfected with pcDNA3.1 and pSARS-PLpro were analyzed the production of TGF-β1 and type I collagen using Western blot, realtime RT-PCR and Sirius red staining assays (Fig. 1) . To examine whether SMAD-dependent pathways involve in TGF-β1mediated up-regulation of Type I collagen in response SARS-CoV PLpro, subcellular localization of receptor-regulated SMAD3 and inhibitory SMAD7 in transfected cells were detected using the immunofluorescent and DAPI staining (Fig. 4) . To examine the possible pathways involved in TGF-β1-dependent up-regulation of Type I collagen by SARS-CoV PLpro, the profiles of ubiquitin-conjugated proteins in transfected cells with vector control and pSARS-PLpro were determined using immune-precipitation and nanoLC-MS/MS. Subcellular localization analysis demonstrated that SMAD3 was predominant in cytoplasmic, but not in the nucleus in transfected cells with pSARS-PLpro compared to vector control (Fig. 4) , revealing that canonical Smad-dependent signaling pathway was not involved in PLpro-induced TGF-β1-dependent upregulation of Type I collagen.
cord-260107-gqbtkf0x	2015	In the present study, one Korean PEDV strain, KOR/KNU-141112/2014, was successfully isolated and serially propagated in Vero cells for over 30 passages. Our genomic analyses indicated that the Korean isolate KNU-141112 is genetically stable during the first 30 passages in cell culture and is grouped within subgroup G2b together with the recent re-emergent Korean strains. Our data indicated that KNU-141112 isolate is relatively stable during the first 30 passages in cell culture and is classified into subgroup G2b that includes PEDV strains responsible for recent severe outbreaks in Korea and the US. Although virus isolation in cell culture from clinical samples of naturally or experimentally infected pigs is fastidious, recent studies reported the successful isolation and propagation of several US original PEDV strains using Vero cells (Chen et al., 2014; Oka et al., 2014) . Cell culture isolation and sequence analysis of genetically diverse US porcine epidemic diarrhea virus strains including a novel strain with a large deletion in the spike gene
cord-260422-z22t57ju	2012	Today''s view is that RNA chaperones are nucleic acid binding proteins present in all living organisms, including viruses, where they Abbreviations: HIV-1, human immunodeficiency virus-type I; NCp7, nucleocapsid protein of HIV-1; ZF, zinc finger; NA, nucleic acid; TAR, transactivation response element; PBS, primer binding site; AA, amino acids. The substantial nucleic acid chaperone properties exhibited by Tat may account for its ability to promote the annealing of the primer tRNA to the viral RNA (Kameoka et al., 2002) and intervene in the first strand transfer (Boudier et al., 2010) and by this way, to stimulate RTion as does NCp7 (Harrich et al., 1997; Ulich et al., 1999; Apolloni et al., 2007) . Human immunodeficiency virus Type 1 nucleocapsid protein (NCp7) directs specific initiation of minusstrand DNA synthesis primed by human tRNA(Lys3) in vitro: studies of viral RNA molecules mutated in regions that flank the primer binding site
cord-260835-ck9z5xsd	2017	Results showed PEDV infection was restricted to pAPN and pAPN domain VII expressing NIH3T3 cells. Also, PEDV harvested from pAPN or domain VII expressing NIH3T3 cells was induced indirect plaques in Vero cells confirming successful entry and replication. In the current study, by constitutive expression of pAPN in non-susceptible NIH3T3 cells, we have sought to annotate the previous findings stipulating pAPN receptor function for PEDV. Susceptibility assays showed infection in pAPN domain-VII expressing cells but virus entry was abrogated in absence of seventh domain (pAPN DI-VI ) as shown in (Fig. 5A) . PEDV was also reported to interact with pAPN in porcine enterocytes (Li et al., 2009) , and is capable of infecting MDCK and ST cells expressing the pAPN receptor (Oh et al., 2003; Nam and Lee, 2010) . In our study, to determine the specific interactive point of pAPN wt with PEDV, domain mutants were expressed stably in NIH3T3 cells.
cord-261388-d56ci0hl	1999	Previous studies in vitro of the processing of cloned polyprotein fragments from the coronavirus infectious bronchitis virus (IBV) large open reading frame (ORF1), confirmed the activity of a predicted 3C-like proteinase (3CLP) domain and suggested that the proteinase is released autocatalytically from the polyprotein in the form of a 35 kDa protein, 3CLpro, capable of further cleavages in trans. The bacterial expression system described utilises the minimum processing unit identified in our previous studies which established that, in addition to the 3CLP domain, MP2 protein sequence between the Q/S 4 cleavage target and a point delimited by an NcoI restriction site (ntd position 10118) was that minimally required for processing. Identification of a 24-kDa polypeptide processed from the coronavirus infectious bronchitis virus 1a polyprotein by the 3C-like proteinase and determination of its cleavage sites
cord-262760-mf1pn587	2020	By analyzing sequence data deposited between December 2019 and end of May 2020, we have compared nucleotide sequences of 570 SARS-CoV-2 genomes from China, Europe, the US, and India to the sequence of the Wuhan isolate. More specifically, the absence of the distinct hotspot mutations in the majority of sequences from samples isolated in China, convincingly argues against the possibility of technical problems during the generation of SARS-CoV-2 nucleotide sequences. and predominate in human populations with different geographic, societal, and genetic backgrounds At the time of beginning our analyses, about 2.500 nucleotide sequences of SARS-CoV-2 had been published of which 570 were randomly selected and compared to the reference sequence of the Wuhan isolate from late 2019 (NCBI Reference Sequence: NC_045512.2). The data on the analyses of 112 isolates from the US confirmed the steady rise in mutation frequencies as SARS-CoV-2 spread to different parts of the world (Table S4 ).
cord-263178-lvxxdvas	2018	To study the roles of hypervariable regions (HVRs) in receptor-binding subunit S1 of the spike protein, we manipulated the genome of the IBV Beaudette strain using a reverse genetics system to construct seven recombinant strains by separately or simultaneously replacing the three HVRs of the Beaudette strain with the corresponding fragments from a QX-like nephropathogenic isolate ck/CH/LDL/091022 from China. We could not detect the replication with ck/CH/ LDL/091022 in Vero cells, so the neutralization tests were performed in 9-day-old SPF embryonated eggs to confirm whether the serotypes of the recombinant IBVs belonged to ck/CH/LDL/091022. Viral antigen was observed in Vero cells infected with the Beaudette strain and the seven recombinant IBVs (Fig. 1b) . S1 gene sequencing results confirmed that the heterogenous HVRs were stably maintained in the recombinant IBVs (Sup Fig. 1) , and no additional mutations were detected in the S protein after three passages in cells or eggs.
cord-263439-oquk4t96	2014	Similar to other coronaviruses, PEDV spike protein mediates its cell entry by binding to cellular receptors and inducing membrane fusion between viral envelopes and cellular membranes. Taken together, our findings reveal that PEDV enters Vero cells via clathrin-mediated endocytosis and requires serine proteolysis during infection. Based on these observations, we concluded that an exogenous protease, like trypsin, was necessary to induce cell-cell fusion in PEDV-infected Vero cells but not essentially required for virus-cell entry. So, we hypothesized that PEDV entry into Vero cells under the trypsin-free condition most likely occurred inside endosomal compartments where cellular proteases might operate similar to trypsin, facilitating S-mediated fusion of PEDV with the endosomal membrane. The infection inhibition assay using various substrates that interfere with endocytosis or lysosomotropic agents revealed that PEDV enters Vero cells via clathrin-mediated endocytic uptake and delivery of virus to an acidic intracellular compartment.
cord-266025-bkm486jd	2012	Based on available data, bats appear to harbor a great diversity of CoVs. The frequency and diversity of CoV detection in bats, now in multiple continents, suggest that bats are likely a source for CoV introduction into other species globally and possibly play an important role in the ecology and evolution of CoVs. Recently we reported the identification of 41 divergent CoVs in bats from Kenya, based on limited ORF1b sequences (Tong et al., 2009) . The aa distances in the 816 bp fragment of the RdRp gene from the Kenya bat CoVs described in this study were compared to the aa sequences from their close reference viruses (Table S2) . In conclusion, sequence data for the structural and nonstructural ORFs in the 3 -end of the genome of seven Kenya bat CoVs confirmed the high diversity and their phylogenetical placement into Alphacoronavirus and Betacoronavirus genera. Genomic characterization of severe acute respiratory syndrome-related coronavirus in European bats and classification of coronaviruses based on partial RNA-dependent RNA polymerase gene sequences
cord-266453-v1hbust8	2012	We have previously described the efficient homologous recombination system between 5′ subgenomic RNA3a (sgRNA3a) and genomic RNA3 of Brome mosaic virus (BMV) in barley protoplasts (Sztuba-Solińska et al., 2011a). A structured region near the 3 sgRNA3a polyA tail, referred to as the intergenic Bbox motif, participates in the assembly of the BMV replicase complex on RNA3 via interactions with protein 1a (Baumstrak and Ahlquist, 2001) , and it binds CP molecules via a specific peptide domains, as mapped by Yi et al. In a separate experiment, the Bbox-RNA3 was co-transfected with SG construct to determine whether the presence of the wt Bbox motif in sgRNA3a could rescue the previously reported high recombination frequency for unmutated RNAs. Indeed, among 100 cDNA clones, there were 42 recombinants (Fig. 2B) , of which the majority carried all three marker restriction sites (74%, 32 clones), while few had either single (BamHI -four clones) or double (BamHI/HindIII -three clones, BamHI/PstI -one clone, HindIII/PstI -two clones) restriction sites.
cord-267228-g2tf1jz6	2018	Mice were immunized by lavage administration of the recombinant NC8-pSIP409-pgsA''-S-DCpep, which was observed to induce DC activation and high production of sIgA and IgG antibodies in experimental animals, while also eliciting production of significantly more IgA(+)B220(+) B cells. Compared with the saline group, the expression level of CD11c + CD40 + of DCs surface molecules in the LP cells of the small intestine was significantly increased in the NC8-pSIP409-pgsA''-S-DCpep group (P < 0.01) and NC8-pSIP409-pgsA''-S-Ctrlpep group (P < 0.05) experimental groups (Fig. 2B) . Unexpectedly, the level of IFN-γ in the supernatant of MLN cells cultured with the strains expressing S-DCpep was significantly higher in the group of mice orally immunized with recombinant NC8-pSIP409-pgsA''-S-Dcpep compare to the group of mice orally administered with saline (P < 0.01), NC8-pSIP409-pgsA''-S-Ctrlpep and NC8-pSIP409-pgsA'' groups (P < 0.05) (Fig. 6B ).
cord-267362-l4288mxw	2010	title: Porcine reproductive and respiratory syndrome virus (PRRSV) could be sensed by professional beta interferon-producing system and had mechanisms to inhibit this action in MARC-145 cells The obtained results showed that PRRSV nsp1 could inhibit Poly(I:C)-induced IFN-β promoter activity in MARC-145 cells by down-regulating the protein level of IRF-3 and inhibiting the phosphorylation of IRF-3. These PAMPs recruit different adaptor proteins, for example, TLRs recruits the adaptor molecule myeloid differentiation primary-response gene 88(MyD88) and Toll/IL-1 receptor domain-containing adaptor inducing IFN(TRIF) while RIG-I recruits virus-induced signaling adapter (VISA), to make TANK-binding kinase 1 (TBK1) or IB kinase-(IKK-) phosphorylate IRF-3 and finally to induce IFN-␤ transcription (Bowie and Unterholzner, 2008) . So, the purpose of the present experiments is to analyze the patterns of IFN-␤ promoter activity in MARC-145 cells during infection with PRRSV and to analyze whether PRRSV nsp1 and N protein could inhibit IFN-␤ production.
cord-267363-5qri915n	2018	As well as having a transformative impact on studies of virus evolution, meta-transcriptomics presents major new challenges for virus classification, with the greater sampling of host taxa now filling many of the gaps on virus phylogenies that were previously used to define taxonomic groups. As well as having a transformative impact on studies of virus evolution, meta-transcriptomics presents major new challenges for virus classification, with the greater sampling of host taxa now filling many of the gaps on virus phylogenies that were previously used to define taxonomic groups. As well as greatly expanding our knowledge of virus diversity, including the ''dark matter'' of highly divergent viruses that often elude characterization, these new data will enable us to determine the fundamental evolutionary and ecological processes that shape the virosphere, and better understand the virus-host interactions that lead to disease emergence.
cord-268010-1m5h3krw	2016	However, a recent study reported evidence of antigenic cross-reactivity between PDCoV Michigan/8977/2014 strain and PEDV, possibly sharing at least one conserved or similar epitope on their N proteins, as determined by enzyme-linked immunosorbent assay (ELISA) and western blot using monoclonal PEDV and PDCoV N-specific antibodies, whereas no cross-reactivity was detected when virus neutralization, indirect immunofluorescence, and immunostaining assays were conducted on either virus-infected cells or intestinal tissues using pig hyperimmune antisera to PEDV or PDCoV (Ma et al., 2016) . Another study using conventional 5-day-old pigs and a cell culture-adapted PDCoV USA/IL/2014 strain (P11) reported the onset of diarrhea at PID 5 in 5 of 5 pigs orally inoculated with 3 × 10 4 TCID 50 /pig of the virus, which was 1 day later or coincided with the detection of viral RNA in feces at PID 4 (3/5 pigs tested) or 5 (2/5 pigs tested) (Chen et al., 2015b) .
cord-268337-o6lo55o8	2005	Human immunodeficiency virus-1 (HIV-1) infection of cells resulted in partial cleavages of eIF4GI that was mapped to three sites in two regions on either side of the eIF3-binding domain ( Fig. 1) (Ohlmann et al., 2002; Ventoso et al., 2001) . Translation assays based on luciferase reporter constructs in cells indicated that expression of HIV protease (HIV PR) primarily inhibited translation of capped mRNAs. Interestingly, comparison of translation function of eIF4GI C-terminal cleavage products produced by L pro and HIV PR revealed that the slightly shorter HIV PR-derived fragment was defective in supporting translation of the PV-IRES but not the EMCV IRES. Demonstration in vitro that eucaryotic initiation factor 3 is active but a cap-binding protein complex is inactive in poliovirus-infected HeLa cells Eukaryotic initiation factor 4GII (eIF4GII), but not eIF4GI, cleavage correlates with inhibition of host cell protein synthesis after human rhinovirus infection Cleavage of eukaryotic initiation factor eIF4G and inhibition of host-cell protein synthesis during feline calicivirus infection
cord-268930-y1cm58r6	2006	To allow the biochemical and structural characterization of the chymotrypsin-like "main proteinase" (non-structural protein 4; nsp4) of the arterivirus prototype Equine Arteritis Virus (EAV), we developed protocols for the large-scale production of recombinant nsp4 in Escherichia coli. In a synthetic peptide-based activity assay, the potential of the recombinant proteinase to cleave peptides mimicking the P9–P7′ residues of six nsp4 cleavage sites was investigated. To test whether active recombinant proteinases had been isolated, the proteolytic activity of purified MBP-nsp4 and nsp4His was tested in cleavage assays using in vitro synthesized substrates as described in Section 2. Although it was reported that the addition of six His residues strongly inhibited the enzymatic activity of the human coronavirus 229E 3CL pro proteinase (Ziebuhr et al., 1997) , in both our assays the catalytic activity of nsp4His was very comparable to that of partially purified uncleaved or cleaved MBP-nsp4.
cord-270064-hidirfkv	2020	In order to gain insight into the emergence, evolution and adaptation of SARS-CoV-2 viruses, a comprehensive analysis of genome composition and codon usage of βCoV circulating in China was performed. In order to gain insight into the emergence, evolution, adaptation and spread of the SARS-CoV-2 viruses, a comprehensive analysis of genome composition and codon usage of βCoV circulating in China was performed. To gain insight into the biology and evolution of emerging SARS-CoV-2, a comprehensive analysis of genome composition, codon and amino acid usage of βCoV strains isolated in China from humans, bats, civets and ferret hosts was performed, including SARS-CoV-2 strains recently isolated from current outbreak. The results of these studies revealed that SARS-CoV-2 strains enrolled in these analyses have a distinct genome composition in relation to other βCoV strains isolated from human (SARS-CoV), bats, civets and ferrets (see Fig. 1 ).
cord-271568-qgpi2kcs	2010	Genomic diversity and the Abbreviations: CPE, cytopathic effects; EID50, 50% embryo infectious dose; ELISA, enzyme linked immunosorbent assay; HMA, hexamethylene amiloride; IBV, infectious bronchitis virus; MHV, mouse hepatitis virus; PBS, phosphate buffered saline; RFLP, restriction fragment length polymorphism; RT-PCR, reverse transcriptasepolymerase chain reaction; SARS-CoV, Severe Acute Respiratory Syndrome virus; SPF, specific pathogen free; TCID50, 50% tissue culture infectious dose. Clinical signs were observed in all of the Mass41 virus challenged groups of birds regardless of treatment but in the intranasal and spray treated groups, fewer birds had signs and the signs were milder, as reflected by lower average scores (Table 1) . Virus was detected in 1 of 5 vaccinated birds in the treated group at 7 days post-vaccination Table 3 Experiment 4: clinical signs a in broiler chickens challenged with IBV at various times after treatment with QR448(a) at 1 day of age.
cord-272383-pzivb0ro	2000	In an effort to optimize the expression, we have constructed several BAV-3 recombinants carrying the hemagglutinin esterase (HE) gene of bovine coronavirus (BCV) in the E3 region with or without exogenous transcription control elements. During infection of bovine cell lines, such recombinant BAVs produced large amounts of glycoprotein gD (a DNA virus gene), which has been shown to undergo proper post-translational modifications . This new transfer vector has two unique restriction enzyme sites (SrfI and SalI) for cloning of foreign genes and an overlap of 1992 bp on the left side and 3866 bp on the right side of the E3 region for efficient homologous recombination with plasmid pFBAV-302 , which dramatically increased the frequency of recombination in BJ 5183 cells. Our initial attempts to insert the BCV HE gene in the E3 region of plasmid pFBAV302 (E3 deleted full length BAV-3 genomic clone; Zakhartchouk et al., 1998) by homologous recombination in E.
cord-272408-8flsy5o1	2020	The neutralizing activity of the rabbit and mouse anti -NTD, -CTD, and -S2 polyclonal antisera was assessed 4 weeks after the initial inoculation by a FFN assay, as previously described (Okda et al., 2015) . Sera from rabbits inoculated with NTD, CTD, and S2 were tested for neutralizing antibodies against PDCoV by ELISA, virus neutralization (VN), and fluorescent focus neutralization (FFN) assays. These results demonstrate that the NTD, CTD, and S2 proteins induced potent anti-PDCoV neutralizing antibody responses in the immunized animals. We found that three regions in PDCOV S protein, including NTD (aa 50-286), CTD (aa 278-616), and S2 (aa 601-1087), can induce neutralizing antibody responses, and the specific polyclonal mouse and rabbit sera efficiently inhibit PDCoV entry and infection in ST cells. Cell attachment domains of the porcine epidemic diarrhea virus spike protein are key targets of neutralizing antibodies
cord-272458-72dybi7t	2007	Moreover, like primary monocytes and macrophages, the THP-1 cells were highly susceptible to HCoV-229E-induced cell death, regardless of the state of differentiation, as mitochondrial metabolic activity dropped significantly at 72 hpi ( Fig. 1C) , suggesting that the decrease in infectious titers may in part be due to a lower number of viable cells. Also, similarly to primary monocytes and macrophages, the PMA-differentiated THP-1 cells restricted HCoV-OC43 replication, with no detection of production of infectious virus (Fig. 1B ) or viral antigens (data not shown). When HCoV-229E infection of human primary monocytes/macrophages was performed at a MOI of 1, infectious virus was under the detection limit at 3 dpi but viral antigens were still easily detected within the infected cells until at least 5 dpi (data not shown). When HCoV-229E infection of both primary monocytes and THP-1 cells was performed at a MOI of 0.1, the kinetics of infection was similar, as shown by infectious virus production ( Fig. 2A) and detection of viral antigens (Fig. 3A) .
cord-272729-nbgdmavr	2012	Investigations into the mechanism of action of ribavirin against PRRSV and PEDV revealed that the addition of guanosine to the ribavirin treatment significantly reversed the antiviral effects, suggesting that depletion of the intracellular GTP pool by inhibiting IMP dehydrogenase may be essential for ribavirin activity. Further experiments revealed that suppression of ribavirin affects post-entry steps of the replication cycle of PRRSV and PEDV, including viral genomic and sg RNA synthesis, viral protein expression, and virus production. Several mechanisms of action for the antiviral activity of ribavirin have been suggested, including a reduction in cellular GTP pools via inosine monophosphate dehydrogenase (IMPDH) inhibition and increased mutation frequency on the virus genome leading to error catastrophe (Graci and Cameron, 2006) . Treatment of cells with ribavirin resulted in significant attenuation of postentry steps during the replication of porcine nidovirus, as determined by lower progeny production, diminished viral protein expression, and decreased synthesis of genomic RNA and sg mRNA.
cord-275016-ij5yaqkx	2005	The recombinant 3C-like protease of Chiba virus, a Norovirus, expressed in Escherichia coli cells was purified and characterized as to effects of pH, temperature, salt contents, and SH reagents on its proteolytic activity. The DNA fragment encoding all residues (Ala1 to Glu181) of the Chiba virus 3C-like protease was amplified by PCR, in that NdeI and Aor51HI restriction sites were introduced at the 5 and 3 ends, respectively. In order to observe proteolysis at the cleavage site between the 3C and 3D, we at first used the His-3CD-C139A mutant protein expressed from pT7His3CD-C139A as a substrate, which was the N-terminal His-tagged 3CD fragment containing the Ala mutation of active-site Cys139 of the 3C-like protease (Fig. 1B) . They used bacterially expressed 3C-like protease with its C-terminus His-tagged as an enzyme and the entire ORF1 protein or 3CD fragment containing the active-site Cys mutation as a substrate which was expressed in the in vitro transcription/translation reaction.
cord-275182-cmjfqkjz	2010	
cord-275413-e2rhioty	2010	The purpose of this study was to characterize the interaction between PRRSV and the pig fetus by (1) identifying sites of virus replication, (2) measuring immune and inflammatory cytokines in different compartments, and (3) evaluating the response of lymph nodes. Maternal, accessory and fetal tissues were collected and stored in formalin for histological staining and immunohistochemistry (IHC), or storage in RNAlater (Ambion) for RT-PCR of cytokine mRNAs. PRRSV-specific antibody was measured in sera using the HerdCheck ® PRRS ELISA (IDEXX) and performed by personnel at Kansas State University Veterinary Diagnostic Laboratory. As shown in Fig. 4A , IFN-␥ and TNF-␣ PCR products were not detected in lung, lymph node or placenta from the non-infected fetuses. To determine if cytokine gene expression was the direct result of PRRSV infection, RT-PCR for IFN-␥ and TNF-␣ was performed on the same tissues from fetuses of infected dam no.
cord-276198-psjua913	2015	
cord-278939-z6kiee09	2020	As previous work has highlighted the potential of traditional Chinese medicines as a source of potential novel drugs (Ling, 2020) , we have not included details on such studies investigating the antiviral activity of remedies comprising portions of numerous plant species in this review. (2020) virtually screened 83 compounds found in Chinese traditional medicines for activity against the RNA-dependent RNA polymerase of SARS-CoV-2, identifying theaflavin, an antioxidant polyphenol, as a potential inhibitor. Several authors have utilised virtual computer docking models to screen for potential compounds that could bind to and inhibit key proteins present in SARS-CoV (Liu and Zhou, 2005; Toney et al., 2004; Wang et al., 2007) , highlighting the potential antiviral activity of compounds such as sabadinine and aurantiamide acetate. Several large in vitro screening studies searching for inhibitory activity of naturally occurring compounds against SARS-CoV have been performed, mainly on Chinese medicinal herbs (Li et al., 2005; Wang et al., 2003) .
cord-279827-921kvrrz	1999	
cord-279849-zzkliu76	2010	
cord-279969-5nlmljcw	2003	
cord-280643-n8qjorqk	2005	To circumvent the problem that mutation in HBV genome may result in resistance when siRNA is further developed as an anti-viral drug, in this study, we established a dual small interfering RNA (siRNA) expression system, which could simultaneously express two different siRNA molecules that can specifically target two genes. To test the effectiveness of this system, we applied this new approach to express simultaneously two different 21-bp hairpin siRNA duplexes that specifically attack the HBs and HBx genes of HBV, respectively, in Bel-7402 and HepG2.2.15 cells. Results indicated that dual siRNA could simultaneously inhibit the expression of HBs and HBx gene by 83.7% and 87.5%, respectively, based on luciferase assays. Results indicated that the levels of HBV core associ-ated DNA were significantly decreased in the cells transfected by HBSXsiRNA, HBS 1 siRNA, HBS 2 siRNA, and HBX 2 siRNA with reduction rate of 90.2%, 85.7 %, 81.3%, and 60.4%, respectively, compared with that of vector control (Fig. 5a) .
cord-281101-gv1sgbk1	2006	
cord-281526-7t9e4lgn	2016	title: Immunogenicity and protective efficacy of recombinant fusion proteins containing spike protein of infectious bronchitis virus and hemagglutinin of H3N2 influenza virus in chickens To investigate whether the recombinant proteins could induce better immune response against IBV infection, we detected IBVspecific antibody in the sera of vaccinated chicken using indirect ELISA. Two weeks after booster vaccination (day 28), the levels of anti-IBV antibodies increased further in chickens immunized with inactivated M41 virus, rS1, rS1-H3(TM) and rS1-HA2. After challenged with virulent IBV M41 strain, our results demonstrated that fusion proteins performed better protection compared with inactivated M41 vaccine and recombinant rS1 protein alone, while the latter groups presented similar protection ratio. The S1 glycoprotein but not the N or M proteins of avian infectious bronchitis virus induces protection in vaccinated chickens Induction of protective immunity in chickens vaccinated with infectious bronchitis virus S1 glycoprotein expressed by a recombinant baculovirus
cord-284479-75zgljet	2019	Thus, the antiviral activity of cyclosporine A (CsA) and some of its nonimmunosuppressive analogs against these viruses has been shown to be related to its ability to bind cellular cyclophilins and inhibiting the interaction with the viral proteins (Bienkowska-Haba et al., 2009; Bose et al., 2003; Damaso and Moussatche, 1998; Franke et al., 1994; Kaul et al., 2009; Nakagawa et al., 2004; Thali et al., 1994; Wainberg et al., 1988; Yang et al., 2008) . CsA has also been reported to inhibit the propagation of several strains of influenza A virus in cell cultures blocking a late step of the replication cycle by mechanisms that might implicate CypA-dependent and -independent pathways (Hamamoto et al., 2013; Liu et al., 2012a; Ma et al., 2016) . Therefore, further studies are needed to better understand the mode of action of AgNPs, their cell specificity and toxicological issues in order to generate new and more effective compounds as well as the use in combination with other drugs in the treatment of different viral diseases.
cord-284866-66azyje4	2011	The first axis in COA is highly correlated with the GC 3 S and GC 12 values in HAV ORFs. This result reveals that nucleotide composition plays an important key role in the codon usage bias observed in HAV ORFs (see Table 2 ). These observations indicate that the composition of dinucleotides also plays a key role in the variation found in synonymous codon usage among HAV ORFs. To study the possible effects of CpG under-representation on codon usage bias of HAV ORFs, the RSCU value of the eight codons that contain CpG (CCG, GCG, UCG, ACG, CGC, CGG, CGU, CGA) were analyzed. The results of these studies revealed that codon usage in HAV ORFs is quite different from that of human genes (see Table 1 ). Positions of the 30 HAV ORFs in the plot of the first two major axes by correspondence analysis (COA) of relative synonymous codon usage (RSCU) values.
cord-285180-32bxx94u	2015	
cord-285580-gq7400tq	2020	In this mini-review, we discuss recent progress concerning the antivirus activity of NO in clinical, pre-clinical and research settings, and its beneficial effects in the treatment of clinical complications in patients infected with coronaviruses and other respiratory viral diseases, including COVID-19. Although positive biological effects have been reported for the administration of NO donors, further studies are required to better evaluate the levels of inflammatory mediators and the activity of important heme-containing enzymes, such as indoleamine 2,3-dioxygenase (IDO), directly involved in the inflammatory responses in respiratory viral infections (Anderson and Russel, 2020) . In other words, NO demonstrates potential for the treatment of patients infected with COVID-19 both in severe and nonsevere conditions, improving oxygenation and antiviral mechanisms, and preventing aggravation of the disease (Ferrari et al., 2020; Parikh et al., 2020) . Protocol of a randomized controlled trial testing inhaled nitric oxide in mechanically ventilated patients with severe acute respiratory syndrome in COVID-19 (SARS-CoV-2)
cord-286416-8eu6wp9b	2012	If deadenylation (e.g., CCR4/Not1), destabilization (e.g., TTP/XRN1) and decapping (e.g., DCP1/DCP2) complex; and even RISC (Ago) complex are recruited to mRNA, these will be targeted to PBs. Conversely, if TIA-1/TIAR or proteins such as G3BP/USP10 are recruited to the stalled initiation complexes, these will be directed to SGs. Different pathways in SG assembly are described (in red): (i) phosphorylation of eIF2␣ induced by the exposure to different stress inducers (e.g., arsenite and thapsigargin) (Fig. 1) ; (ii) Hippuristanol and Pateamine A, drugs that inhibit the helicase activity of eIF4A altering ATP binding or ATPase activity; and (iii) the overexpression of SG markers, such as G3BP or TIA-1. West Nile virus infections suppress early viral RNA synthesis and avoid inducing the cell stress granule response Interaction of TIA-1/TIAR with West Nile and dengue virus products in infected cells interferes with stress granule formation and processing body assembly
cord-286473-sl5zy8nj	2008	
cord-286658-9kco7qad	2018	Recently, numerous IBV strains have been identified and new genotypes/serotypes have emerged from existing viruses via point mutations, insertions, and deletions in the viral genome, especially in the S1 subunit of the spike protein gene. There have been several episodes of infectious bronchitis (IB) in Chinese chicken flocks, and the genotypes/serotypes of IBVs were previously classified based mainly on the nucleotide sequences of genes encoding the S1 subunit of the spike protein (Han et al., 2011) , and in some cases based on cross virus-neutralization Chen et al., 2017) in China. In addition, it is very interesting to note that the/I1101/16 isolate exhibited decreased replication levels in both the tracheal and kidney tissues (two target tissues for most IBVs) compared with one of its parental viruses (the ck/CH/LHLJ/140901 strain, which does not cause severe clinical disease in SPF chickens), but it exhibited prolonged replication and shedding post-challenge in a Table 3 Pairwise comparisons of the nucleotide sequences of the S2 subunit of the spike genes between the 4/91 vaccine strain, I1101/16 isolate, and pathogenic 4/91 strain a .
cord-286703-ipoj13va	2017	Data from cell culture infection models (Chan et al., 2013a (Chan et al., , 2013b de Wilde et al., 2013b; Falzarano et al., 2013a; Kindler et al., 2013; Zielecki et al., 2013) and experiments in rhesus macaques (Falzarano et al., 2013b) and marmosets (Chan et al., 2015) suggested that interferons (IFNs) are potent inhibitors of MERS-CoV replication. As ribavirin has previously been reported to inhibit MERS-CoV replication (Falzarano et al., 2013a) and ALV and ribavirin have been used together during clinical trials for hepatitis C treatment (Pawlotsky et al., 2015) , this combination was tested in LLC-MK2 cells. (e, f) SARS-CoV-infected (e) Vero or (f) VeroE6 cells (MOI 0.01) were treated with various concentrations of ALV from 1 h p.i. onwards, and virus titers in the culture medium at 32 h p.i. were determined by plaque assay.
cord-287324-ecpicv5v	2017	In this study, we detected the viromes of RNA viruses of one mock sample, one pooled duck feces sample and one pooled mink feces sample on the Personal Genome Machine platform using the sequencing libraries prepared by three methods. In this study, we detected the viromes of RNA viruses of one mock sample and two pooled authentic samples, using the libraries prepared by the three methods on the Personal Genome Machine (PGM) platform, with the aim to generate data of significance for virome detection of RNA viruses and characterize the viromes of RNA viruses in ducks and minks. In the future, it is of significance to compare methods 2 and 3 in detecting viromes of RNA viruses in some clinical samples containing limited viral RNA. Detection of viromes of ducks and minks increases our understanding of the viral diversity in the animals, and provides novel clues for further studies regarding diagnosis of infectious diseases, identification of novel viruses and research of host-virus relationships.
cord-288253-wqrhiq08	2015	Because the major pathological changes of the porcine coronaviruses (e.g., TGEV and PEDV) involves enteric diseases, we measured porcine APN expression in the small intestine by RT-PCR, immunoblotting, and IHC. An immunohistochemical analysis, with both anti-Flag and anti-porcine APN antibodies, clearly confirmed porcine APN expression in the brush borders of the absorptive cells in the small intestines of the mouse model (Fig. 4C) . For these purposes, many transgenic mouse models have been developed to study viral pathogenesis, immune responses, and vaccines (Darling et Both wild type and porcine APN transgenic mice were infected with PEDV (5X TCID5010 6 ) orally on day 0. Although significant clinical illness was not observed when the transgenic mice were infected with PEDV, their susceptibility to the virus was confirmed by the detection of viral RNA in various organs with RT-PCR and viral proteins in the small intestines with IHC.
cord-290481-i2ppvsh5	2006	It was concluded that, at least in part, viral pathogenicity is due to interference of silencing suppressors with developmental function of plant small RNAs. Despite their mechanistic similarity, p21 and p19 appear to be structurally and evolutionarily unrelated and neither has detectable homologues outside the respective virus genera (Vargason et al., 2003; Ye and Patel, 2005) . Although Citrus tristeza virus (CTV) encodes p20, a p21like suppressor of RNA silencing, screening of the CTV genome revealed an additional suppressor, p23, that has no homologues in other closteroviruses (Fig. 2) (Lu et al., 2004) . A comparison of TMV and BYV, which both evolved from the alphavirus-like ancestors, shows that the large part of the ∼9 kb genomic surplus of BYV is dedicated to facilitating the synthesis of the virion RNA and multiple sgRNAs. The rest of the surplus was invested in the formation of the complex virion tail that empowers virus transport within and transmission between the host plants and in suppression of RNA silencing (Fig. 1) .
cord-290801-dv6aak01	2012	Since the core protein of flaviviruses is also endowed with potent RNA chaperone activities, we decided to examine the effect of West Nile virus (WNV) core on 5′–3′ genomic RNA annealing in vitro. These results indicate that core protein – besides its function in viral particle formation – might be involved in the regulation of flavivirus genomic RNA cyclization, and thus virus replication. In this study, we examined the effect of WNV core protein chaperoning on viral 5 -3 UTR annealing, using an in vitro model system with separate 5 and 3 RNAs. We found that core protein binding greatly increases the rate of 5 -3 complex formation, and is required for the interaction when full-length 3 UTR RNAs are used (Fig. 2) .
cord-290948-cuu78cvl	2008	Using the combination of yeast two-hybrid screening and GST pull-down assays, we have now analyzed all potential interactions between SARS-Coronavirus nonstructural proteins, which may contribute to the structure and/or function of the viral replication/transcription complex. SARS-CoV nsp3 is a large multidomain protein of 1922 amino acids Thiel et al., 2003) that is thought to contain at least seven domains: (1) an N-terminal Glu-rich acidic domain (AD); (2) an X domain (XD) with poly(ADP-ribose) binding properties Saikatendu et al., 2005) ; (3) the SUD domain (for SARS-CoV Unique Domain, an insertion not found in any other coronavirus thus far) with a specific affinity for oligo(G)-strings (Tan et al., in press); (4) a papain-like protease (PLP2), recently shown to exhibit deubiquitinating activity (Barretto et al., 2005; Harcourt et al., 2004; Lindner et al., 2005; Ratia et al., 2006) ; (5) an unknown domain possibly extending the papain-like protease domain, termed PLnc for Papain-Like noncanonical (see below); (6) a transmembrane domain (Kanjanahaluethai et al., 2007) corresponding to the N-terminal of the Y domain; and (7) the remainder of the Y domain, the abbreviation "Y domain" will be used for this part in this study.
cord-291086-goidlh08	2011	
cord-291754-1zxztadu	2019	In this study, a pathogenic avian infectious bronchitis virus (IBV) QX-type strain YN was successfully rescued by vaccinia virus based reverse genetic technology. To compare the in vitro replication of the rescued virus rYN and its parental strain YN on CEK cells, 200 μl PBS containing 10 3.0 TCID 50 of rYN or YN virus were inoculated onto the CEK cells in 24-well plates, and 200 μl supernatants from three wells from each group were harvested at the time points of 6, 12, 24, 36, 48, and 60 hpi for a real-time PCR detection assay for IBV N gene as described above. Collectively, these results demonstrate the successful rescue of the pathogenic IBV strain YN from cloned cDNA by using electroporation of full-length IBV in vitro transcripts into N-protein expressing cells and subsequent virus amplification in the allantoic cavities of ECE.
cord-291962-rp172ugk	2019	title: Nucleotide-binding oligomerization domain-like receptor X1 restricts porcine reproductive and respiratory syndrome virus-2 replication by interacting with viral Nsp9 To test this, increasing dose of NLRX1 was transfected into Marc-145 cells followed by PRRSV infection, qPCR was then performed to test the total viral RNA levels. On the other hand, recent literature indicated that the interaction of Nsp9 with SUMO E2 conjugating enzyme Ubc9 and cellular protein interleukin-2 enhancer binding factor 2 (ILF2) through its RdRp domain resulted in a significantly decrease of virus titers, indicating that cells utilize host antiviral factors as defense mechanisms to limit PRRSV infection Wen et al., 2017) . An intracellularly expressed Nsp9-specific nanobody in MARC-145 cells inhibits porcine reproductive and respiratory syndrome virus replication Porcine reproductive and respiratory syndrome virus nucleocapsid protein interacts with Nsp9 and cellular DHX9 to regulate viral RNA synthesis The DEADbox RNA helicase 5 positively regulates the replication of porcine reproductive and respiratory syndrome virus by interacting with viral Nsp9 in vitro
cord-293562-69nnyq8p	2018	We consider a deterministic model for the transmission dynamics of the Zika virus infectious disease that spreads in, both humans and vectors, through horizontal and vertical transmission. We consider a deterministic model for the transmission dynamics of the Zika virus infectious disease that spreads in, both humans and vectors, through horizontal and vertical transmission. An in-depth stability analysis of the model is performed, and it is consequently shown, that the model has a globally asymptotically stable disease-free equilibrium when the basic reproduction number R 0 < 1. An in-depth stability analysis of the model is performed, and it is consequently shown, that the model has a globally asymptotically stable disease-free equilibrium when the basic reproduction number R 0 < 1. Since the only way to control the disease is to isolate patients who have been infected with the Zika virus, we included a new population compartment consisting of hospitalized individuals.
cord-294764-v28wbrqp	2017	
cord-295099-ghc85pf5	2018	Antibody responses to neutralize human immunodeficiency virus-1 (HIV-1) are mediated by direct binding to viral spikes, which are trimers composed of glycoproteins gp120 and gp41 (Pincus et al., 2017a; Pincus et al., 2017b; Blair et al., 2007; Morris et al., 2000; Micoli et al., 2000; Pegu et al., 2017; Haynes and Mascola, 2017; Liao et al., 2004; Brodine et al., 2003; Ward and Wilson, 2017; Debnath et al., 1994; Moore et al., 1993) . M43 and m44 are HIV-1 cross-reactive human monoclonal antibodies isolated from a recombinant phage display library by competitive antigen panning (Zhang et al., 2012; Zhang et al., 2008; Zhang et al., 2006; Zhang et al., 2004a; Zhang et al., 2004b) . HIV-1 specific antibodies isolated by display techniques are less potent than those isolated by micro neutralization or single B cell sorting and cloning. Anti-human immunodeficiency virus type 1 human monoclonal antibodies that bind discontinuous epitopes in the viral glycoproteins can identify mimotopes from recombinant phage peptide display libraries
cord-295187-konm26x5	2015	However, two distinct features were observed in the CCoV-I genome: (i) the presence of an additional ORF between the spike (S) protein gene and ORF3a; (ii) the diversity of the S protein, which is more closely related to that of feline coronavirus type I and presents a furin cleavage site. Canine coronavirus (CCoV) is usually responsible for mild enteritis in young dogs Buonavoglia, 2008, 2011) , although fatal disease has been associated to a pantropic variant of the virus (Decaro et al., , 2010a Marinaro et al., 2010; Zicola et al., 2012; Ntafis et al., 2012) . Alignment of complete genome sequences of CCoV-I strain 23/03 and reference alphacoronaviruses showed the closest genetic relatedness with CCoV-IIa isolates (83.82-84.98% nt identity), followed by TGEV (82.81%) and . Molecular characterization of a canine coronavirus NA/09 strain detected in a dog''s organs
cord-299904-i5c6nf18	2009	authors: Cornelissen, E.; Dewerchin, H.L.; Van Hamme, E.; Nauwynck, H.J. title: Absence of antibody-dependent, complement-mediated lysis of feline infectious peritonitis virus-infected cells ADCML consists of virus-specific antibodies that bind to cell surface expressed viral proteins which result in complement activation and cell lysis. ADCML consists of virus-specific antibodies that bind to cell surface expressed viral proteins which result in complement activation and cell lysis. Surprisingly, no lysis was observed in the CrFK cells and the monocytes that do show surface-expressed viral proteins, while controls showed that the ADCML assay was functional. Surprisingly, no lysis was observed in the CrFK cells and the monocytes that do show surface-expressed viral proteins, while controls showed that the ADCML assay was functional. Absence of surface expression of feline infectious peritonitis virus (FIPV) antigens on infected cells isolated from cats with FIP Feline infectious peritonitis virus-infected monocytes internalize viral membrane-bound proteins upon antibody addition
cord-300883-rws11uel	2007	We also observed surprisingly higher nucleotide substitution rates per site, per year for each lineage of hMPV than the rates that were previously reported for the human respiratory syncytial virus, suggesting rapid evolutionary dynamics of hMPV. Although comparative genome mapping analyses suggested that this virus has structural and functional similarities with HRSV (Kahn, 2006) , recent studies reported that the attachment (G) glycoprotein of these paramimyxoviruses exhibit extensive nucleotide and amino acid variation, with most differences located in the extracellular domain (Peret et al., 2004; Kahn, 2006) . Here we used Yang et al''s (2000) ML codon substitution models to test whether there was evidence at the nucleotide sequence level that a subset of amino acid sites in G-protein of hMPV sequences that represent each subgroup has been under positive selection.
cord-301151-f6vya3qh	2020	In this study, the clinical features of COVID-19 patients were analyzed, then 39 respiratory pathogens in their throat swab were detected by specific real-time RT-PCR. 257 patients were diagnosed with the SARS-CoV-2 infection and their clinical severity was classified according to National Health Commission of the People''s Republic of China revised criteria for diagnosis and treatment of novel coronavirus infection pneumonia (trial version fifth, revised version). Below 15 years of age, a total of 11 (4.3 %) were diagnosed with the SARS-CoV-2 infection and there were no case in severe/critical category. In our study, 94.2 % of COVID-19 patients could be co-infected with one or more other pathogens, including 9 viruses, 11 bacteria and 4 fungi. Along with the course of disease, both the rates and pathogen species of co-infection among COVID-19 patients were decreased significantly, which may due to the treatment X.
cord-301301-ilsenpus	2017	Interestingly, this strain possessed unique genetic signatures (including a longer ORF1b/ORF2 overlap and a longer 3′UTR) and it was divergent in both ORF1b and ORF2 from all other canine astroviruses, with the highest nucleotide sequence identity (68% and 63%, respectively) to a mink astrovirus, thus suggesting a possible event of interspecies transmission. A total of 63 samples obtained from 50 animals were tested for AstV by using a pan-astrovirus specific primer set (Chu et al., 2008) as described elsewhere (Mihalov-Kovács et al., 2014) and 37 (from 33 dogs) were randomly selected for viral metagenomics. The complete ORF1b was 1530 nt long in all canine AstVs, except the partially sequenced strain, HUN/2012/8, where a 770 nt long portion was determined. In addition, upon sequence comparison and phylogenetic analysis, strain HUN/2012/8 differed markedly from other canine AstVs concerning the partial ORF1b and the full-length ORF2 (Table 3) .
cord-302083-9q1i20o6	2020	PEDV infection of neonatal pigs causes fecal virus shedding (alongside frequent detection of PEDV RNA in the nasal cavity), acute viremia, severe atrophic enteritis (mainly jejunum and ileum), and increased pro-inflammatory and innate immune responses. Detection of viremia where viral RNA in serum ranged from 4.5-8.6 log10 genomic equivalents (GE)/ml was identified in gnotobiotic neonatal (5/5; 100%), or conventional 9-dayold nursing (16/16; 100%) and 26-day-old weaned pigs (11/20; 55%) infected with a US non-S INDEL PEDV strain at PID 1-5 (Jung et al., 2015a; Jung et al., 2014) . Cross protective immune responses in nursing piglets infected with a US spike-insertion deletion porcine epidemic diarrhea virus strain and challenged with an original US PEDV strain Goblet cell depletion in small intestinal villous and crypt epithelium of conventional nursing and weaned pigs infected with porcine epidemic diarrhea virus.
cord-303111-iv4lzpev	2014	Until recently, the study of CoV genetics was broadly restricted to the analysis of temperature-sensitive (ts) mutants Baric, 1992, 1994; Lai and Cavanagh, 1997; Schaad and Baric, 1994; Stalcup et al., 1998) , defective RNA templates which depend on replicase proteins provided in trans by a helper virus (Izeta et al., 1999; Narayanan and Makino, 2001; Repass and Makino, 1998; Williams et al., 1999) , and recombinant viruses generated by targeted recombination (Masters, 1999; Masters and Rottier, 2005 reverse genetic system devised for CoVs at a time when it was not clear whether the construction of full-length infectious cDNA clones would ever be technically feasible. These reverse genetic systems have been established using non-traditional approaches, which are based on the use of targeted recombination, BACs, in vitro ligation of CoV cDNA fragments, and vaccinia virus as a vector for the propagation of CoV genomic cDNAs. The availability of CoV full-length infectious clones and recombinant viruses expressing reporter genes constitute important tools for the study of CoV replication and transcription mechanisms, virus-host interaction and pathogenesis, and also for the rapid and rational development and testing of genetically defined vaccines.
cord-304137-vxqkztio	2009	We have reported that meliacine (MA), an antiviral principle present in partially purified leaf extracts of Melia azedarach L., exerts an antiviral action on the development of herpetic stromal keratitis (HSK) in mice by causing a significant decrease in the viral load in the eye of Herpes simplex virus type 1 (HSV-1) infected animals, as well as in the incidence and severity of lesions due to a virus-induced immunopathological reaction (Pifarré et al., 2002) . We have found that CDM is able to block HSV-1 induced activation of NF-B by inhibiting its translocation to the nucleus of infected human conjunctival cells (NHC), and postulated that CDM would be able to abolish murine HSK by controlling viral spread and the associated immunopathology as well (Barquero et al., 2006) . The aim of the present study was to determine whether CDM displays an antiviral activity in infected corneal cells, the target of HSV-1 multiplication in vivo, as well as its effect on the translocation of NF-B to the nucleus.
cord-304424-048xo7jn	2018	
cord-309205-l8vjtrjq	2018	The ability to infect and replicate in monocytes/macrophages is a critically distinguishing feature between the two feline coronavirus (FCoV) pathotypes: feline enteric coronavirus (FECV; low-virulent) and feline infectious peritonitis virus (FIPV; lethal). Previously, by comparing serotype II strains FIPV 79-1146 and FECV 79-1683 and recombinant chimeric forms thereof in cultured feline bone marrow macrophages, we mapped this difference to the C-terminal part of the viral spike (S) protein (S2). Despite some concerns relating to the precise identity of the FCoV strains 79-1683 and 79-1146, to be discussed later, but lacking better options to address this critical issue in the pathogenesis of FIP, we continued in the present study with investigating the contributions of the amino acids in the spike S2 domain differing between the prototypic strains to the distinguishing macrophage tropism of these viruses. There are eleven amino acid differences in the C-terminal domain of the S proteins of FIPV 79-1146 and FECV 79-1683 to which we mapped these viruses'' differential ability to infect macrophages (Fig. 1c) .
cord-309428-qkjjxr6p	2015	
cord-311628-ep795pil	2016	Our objective here is to review the novel delivery platform based on Bacteriophage MS2 virus-like particles (VLPs), including introduction to their structure, their potential as a delivery platform, and their expected use in medicine and other fields. A series of research findings showed that an MS2 VLP-based vaccine can effectively induce innate and cognate immune responses and can be used as a specific preventive intervention in some diseases, such as foot-and-mouth disease (Bittle et al., 1982; Dong et al., 2015; Van Lierop et al., 1992; Wong et al., 2000) , prostate cancer (Li et al., 2014) , and illnesses caused by human papilloma virus (HPV) (Tumban et al., 2012) . These particles offer an effective and convenient way to package RNAs, DNAs, epitope peptides, and drugs into bacteriophage capsids, forming different kinds of VLPs. MS2 VLPs can not only deliver various kinds of agents with a good safety profile and strong immunogenicity but also ensure tissue-specific targeting, which is determined by the species of the virus.
cord-312489-ywep0c08	2015	We evaluated the antigenicity of recombinant infectious bronchitis virus (IBV) S1 protein expressed in mammalian cells. Native S1 ELISA detected similar titers in the sera of animals immunized with recombinant S1 protein compared to those in sera of chickens immunized with inactivated virus (Fig. 6b ) (Control experiments (data not shown) demonstrated that mock and unvaccinated control groups did not differ from each other in VN and ELISA tests of anti-S1 activity.) These results indicated that while recombinant S1 protein retained antigenicity (the ability to induce antibodies against S1 protein), the resulting antibodies was decreased its neutralizing activity, in contrast to those induced by inactivated virus. The S1 glycoprotein but not the N or M proteins of avian infectious bronchitis virus induces protection in vaccinated chickens Induction of protective immunity in chickens vaccinated with infectious bronchitis virus S1 glycoprotein expressed by a recombinant baculovirus
cord-312848-vbadg8ki	2004	In the present study, we analyzed the S glycoprotein gene to characterize 10 winter dysentery (WD) coronavirus strains circulated in Korea during 2002–2003 and compared the nucleotide (nt) and deduced amino acid (aa) sequences with the other known BCoV. The phylogenetic analysis of the entire S glycoprotein gene revealed that the aa sequences of all Korean WD strains were more homologous to each other and were very closely related to respiratory bovine coronavirus (RBCV) strain OK and enteric bovine coronavirus (EBCV) strain LY-138, but were distinct from the other known BCoVs. Based on the phylogenetic analysis of the hypervariable region of the S1 subunit, all Korean WD strains clustered with the respiratory strain OK, BCQ3994 and the enteric strain LY-138, while the Canadian BCQ calf diarrhea and WD strains, and the American RBCV LSU, French EBCV F15 and avirulent VACC, L9, and Mebus strains clustered on a separate major branch.
cord-314415-yr0uxok2	2018	In this study, a novel circular replication-associated protein (Rep)-encoding single stranded (CRESS) DNA virus was discovered in diarrheic sample of a calf with severe hemorrhagic enteritis. The result showed that Bo-Circo-like virus CH is clustered into a independent branch with seven reported strains of proposed family Kirkoviridae and eight CRESS-DNA virus strains recently submitted to GenBank database; Bo-Circo-like virus CH is more closely related to Po-Circo-like virus and shows significant genetic differences with viruses in the families Circoviridae, Nanoviridae, Geminiviridae Genomoviridae, Bacilladnaviridae and Smacoviridae (Fig. 3) . The sequence alignments included strain Bo-Circo-like virus CH in this study, representative members of the Circoviridae, Geminiviridae, Nanoviridae, Genomoviridae, Bacilladnaviridae and Smacoviridae families, the proposed new genera of krikoviruses, and still unassigned novel CRESS-DNA viruses with the best BLASTp matchs in GenBank database. The sequence alignments included five Bo-Circo-like virus strains detected in this study and seven reported strains of the proposed family Kirkoviridae.
cord-317061-0bx704ao	2015	
cord-318319-efqf5e1i	2020	The lymphocyte count after ciclesonide treatment in the non-severe pneumonia group was significantly higher (p = 0. Many patients with coronavirus infection disease 2019(COVID-19) are subclinical, and it has been reported that people are J o u r n a l P r e -p r o o f contagious even when asymptomatic [1, 2] , which means preventing the spread of SARS-CoV-2 is challenging [3] . Risk factors of severe pneumonia include age, comorbidities, smoking, reduced lymphocyte count, elevated ferritin levels, and elevated C-reactive protein (CRP) levels [4] [5] [6] [7] [8] [9] . In addition, we examined whether ciclesonide could prevent the development of severe COVID-19 among patients with these predictors. Moreover, the lymphocyte count after ciclesonide therapy in the non-severe pneumonia group was significantly higher (p=0.0156) compared to before treatment (mean 6.14 days, SD 2.17) (Figure 3b ).
cord-320331-wtxja5i9	2020	
cord-325973-e3rxr6oq	2017	Although the current CPV vaccines, derived from the original CPV-2 strains, or CPV-2b strains, have been shown to confer protective immunity against CPV disease, and post-vaccination reactions have rarely been encountered in immunized dogs, the emergence of new genetic and antigenic variants underscores the importance of constant http://dx.doi.org/10.1016/j.virusres.2017.08.008 Received 16 May 2017; Received in revised form 10 July 2017; Accepted 21 August 2017 monitoring of evolution patterns of CPV strains circulating in dogs throughout the world (Decaro and Buonavoglia, 2012; Miranda and Thompson, 2016) . Although the prevalence and genetic diversity of CPV and CCoV in dogs have been extensively studied in different parts of the world including nearby Latin American countries, there are no reports on these important canine viruses from the Caribbean region so far. We report here the detection and molecular characterization of CPV and CCoV strains in dogs with diarrhea on the Caribbean island of St. Kitts (KNA).
cord-326320-flfrdrbi	2020	title: Scaffold morphing of arbidol (umifenovir) in search of multi-targeting therapy halting the interaction of SARS-CoV-2 with ACE2 and other proteases involved in COVID-19 The multi-targeting potential of generated analogues was explored against various targets involved in the pathogenesis of COVID-19 including SARS-CoV-2 SP, ACE2, furin, TMPRSS2 (in viral attachment) and 3CLPro (in viral replication). A cutoff value of 3 was used for the screening of compounds based on synthetic possibility and topranked molecules were submitted to structure-guided drug binding analysis such as molecular docking studies. All these molecules were docked against SARS-CoV-2 SP-ACE2 complex, furin, TMPRSS2 and main protease (3CLPro) and the binding affinity of their docked complexes was also calculated in terms of MM-GBSA score. J o u r n a l P r e -p r o o f 44 A combination of scaffold morphing and a structure-based drug designing approach was successfully utilized to identify putative multi-targeting analogues of arbidol against COVID-19.
cord-326349-59566vqe	2013	In addition, TGEV infection of the cells synchronized in various stages of cell cycle showed that viral genomic RNA and subgenomic RNA, and virus titer were higher in the cells released from S-phaseor G2/M phase-synchronized cells than that in the cells released from the G0/G1 phase-synchronized or asynchronous cells after 18 h p.i. Taken together, our data suggested that TGEV infection induced S and G2/M phase arrest in host cells, which might provide a favorable condition for viral replication. To further determine the roles of p53 in TGEV-induced cell cycle arrest, we investigated the effects of PFT-␣, a specific inhibitor of p53 that does not affect the mRNA levels of TGEV genes (Huang et al., 2013) , on the cell cycle profiles and the expression of p21, cdks and cyclins in TGEV-infected PK-15 and ST cells. As shown in Fig. 6B , pre-incubation of PK-15 and ST cells with PFT-␣ attenuated cell cycle arrest at S and G2/M phase induced by TGEV infection.
cord-327682-i3uim0zi	1999	It has been shown in a number of studies that virtually all the enterovirus serotypes and most of the HRV isolates can be detected using these primer sequences (Hyypiä et , 1989; Horsnell et al., 1995; Pulli et al., 1995; Arola et al., 1996; Huttunen et al., 1996; Pitkäranta et al., 1997; Hyypiä et al., 1998; Oberste et al., 1998) The authors became convinced of the usefulness of this technique during a recent outbreak of aseptic meningitis in Finland. Partial sequence analysis of virtually all enterovirus serotypes has shown that they belong to these four clusters (Pulli et al., 1995; Huttunen et al., 1996) and that the VP4/VP2 region sequence can be used for molecular typing of clinical isolates (Arola et al., 1996) . In hepatitis A virus infections, the molecular epidemiology has been investigated by many reseach groups and an extensive analysis of partial sequences from different geographic locations has been used to establish a useful database for further studies (Robertson et al., 1992) .
cord-329183-s0zrvn9o	2008	title: Sequence analysis of a reovirus isolated from the winter moth Operophtera brumata (Lepidoptera: Geometridae) and its parasitoid wasp Phobocampe tempestiva (Hymenoptera: Ichneumonidae)() When the protein encoded by ObRV Seg-10 was expressed (by inserting the open reading frame into a baculovirus expression vector) no ''occlusion bodies'' were observed in the recombinant baculovirus infected insect cell cultures. Seg-1 of ObRV is 4170 nt in length (Table 1) , with a single large ORF between nt 33 and 4109 (stop codon TGA), coding for a predicted protein of 1358 aa (155.7 kDa), which is identified as VP1. Although the lack of sequence information from this genus (particularly the RdRp), makes it difficult to make further comparisons, the data presented here, together with the detection of an eleventh genome segment in female wasps (Graham et al., 2006) , suggest that ObRV represents a new member (a new species) within the genus Idnoreovirus, which contains other non-occluded insect reoviruses.
cord-330260-xuw31zfn	2009	All of the recombinants showed chimeric IBV genome arrangements originated from Taiwan and China-like parental strains. Phylogenetic analyses were performed based on the nucleotide sequence alignment using each ORF from the S to N genes among eight Taiwan and reference strains (Fig. 1) . Phylogenetic analysis of partial S1 and N gene sequences of infectious bronchitis virus isolates from Italy revealed genetic diversity and recombination Recombinant avian infectious bronchitis virus expressing a heterologous spike gene demonstrates that the spike protein is a determinant of cell tropism A novel variant of avian infectious bronchitis virus resulting from recombination among three different strains Sequence evidence for RNA recombination in field isolates of avian coronavirus infectious bronchitis virus Genetic diversity of avian infectious bronchitis coronavirus strains isolated in China between Genetic grouping for the isolates of avian infectious bronchitis virus in Taiwan
cord-330508-uilejxmi	2020	While molecular details of the innate immune response are well characterized, this research field is now being revolutionized with the recognition that cell metabolism has a major impact on the antiviral and inflammatory responses to virus infections. While molecular details of the innate immune response are well characterized, this research field is now being revolutionized with the recognition that cell metabolism has a major impact on the antiviral and inflammatory responses to virus infections. A detailed understanding of the role of metabolic regulation with respect to antiviral and inflammatory responses, together with knowledge of the strategies used by viruses to exploit immunometabolic pathways, will ultimately change our understanding and treatment of pathogenic viral diseases. A detailed understanding of the role of metabolic regulation with respect to antiviral and inflammatory responses, together with knowledge of the strategies used by viruses to exploit immunometabolic pathways, will ultimately change our understanding and treatment of pathogenic viral diseases.
cord-332075-gxmae2rs	2015	title: Generation and evaluation of a recombinant genotype VII Newcastle disease virus expressing VP3 protein of Goose parvovirus as a bivalent vaccine in goslings In this study, we generated a recombinant rmNA-VP3, expressing GPV VP3 using a modified goose-origin NDV NA-1 by changing the multi-basic cleavage site motif RRQKR↓F of the F protein to the dibasic motif GRQGR↓L as that of the avirulent strain LaSota as a vaccine vector. This is the first study demonstrating that recombinant NDV has the potential to serve as bivalent live vaccine against Goose parvovirus and Newcastle disease virus infection in birds. To evaluate whether this genotype VII isolate could be used as a vaccine vector for geese we generated a recombinant virus rmNA-VP3 expressing VP3 protein of GPV after modifying the polybasic F cleavage site of NA-1 to the dibasic motif of LaSota.
cord-332317-wrztpeb8	2015	
cord-333180-xevie6tm	2015	
cord-335706-lopcb77c	2011	
cord-338602-6n309bnp	2020	title: IFN-γ is an independent risk factor associated with mortality in patients with moderate and severe COVID-19 infection We proposed a study in patients with moderate to severe COVID-19 infection to evaluate the interleukin patterns and its role as prognosis factors. A reasonable hypothesis is that (i) pro-inflammatory innate immunity and (ii) anti-inflammatory system are related to disease severity or death once IL-6, IL-8, and IL10 are closely described as prognostic factors in patients diagnosed with COVID-19 1, 3, 7 . Previous studies have not reported the association between IFN-γ and death, even evaluating the COVID-19-reactive CD69+ expressing IFN-γ producing CD8+ T in 25 patients with severe and moderate disease 22 . Suppressed T cell-mediated immunity in patients with COVID-19: A clinical retrospective study in Wuhan Levels of cytokines from patients with moderate and severe COVID-19 infection according to the outcome (data in the median with IQR)
cord-344084-z4t2wkgk	2020	The genetic variant CCR5Δ32 (32 base-pair deletion in CCR5 gene) impairs CCR5 expression on the cell surface and is associated with protection against HIV infection in homozygous individuals. In this context, this review discusses the involvement of CCR5 and the effects of the CCR5Δ32 in human infections caused by the following pathogens: West Nile virus, Influenza virus, Human papillomavirus, Hepatitis B virus, Hepatitis C virus, Poliovirus, Dengue virus, Human cytomegalovirus, Crimean-Congo hemorrhagic fever virus, Enterovirus, Japanese encephalitis virus, and Hantavirus. In agreement with studies showing that CCR5Δ32 homozygous genotype is a risk factor for symptomatic WNV infection in humans, Ccr5-/-WNV-infected mice showed a reduced capacity of viral control, increased disease severity, impaired leukocyte trafficking towards the brain, and high mortality rates than Ccr5 wild-type mice. In conclusion, although tissue analysis and evidence obtained in vitro suggest that the CCR5 is potentially involved in the pathogenesis of HPV, most studies point to a lack of involvement of CCR5Δ32 in susceptibility to HPV infection or HPV-associated diseases.
cord-345999-iiw4cs8p	2020	Since it is a newly emerging viral disease and obviously there is a lack of anti-SARS-CoV-2 therapeutic agents, it is urgently required to develop an effective anti-SARS-CoV-2-agent.Through recent advancements in computational biology and biological assays, several natural compounds and their derivatives have been reported to confirm their target specific antiviral potential against Middle East respiratory syndrome coronavirus (MERS-CoV) or Severe Acute Respiratory Syndrome(SARS-CoV).These targets including an important host cell receptor, i.e., angiotensin-converting enzyme ACE2 and several viral proteins e.g. spike glycoprotein (S) containing S1 and S2 domains, SARS CoV Chymotrypsin-like cysteine protease (3CL(pro)), papain-like cysteine protease (PL(pro)), helicases and RNA-dependent RNA polymerase (RdRp). For the management J o u r n a l P r e -p r o o f of COVID-19 infection, various molecular targets playing important role in the SARS-CoV-2 life cycle including host cell receptor-Angiotensin-converting enzyme ACE2 (PDB ID 3D0G) and viral proteins such as S protein (containing S1 and S2 domains) (PDB ID 6XM0); various cysteine proteases such as papain-like cysteine protease (PL pro ) (PDB ID 6WX4) or Chymotrypsin like nprotease (3CL pro ) (PDB ID 1P9U), helicases and RNA-dependent RNA polymerase (RdRp) (PDB ID 6M71) could be evaluated .
cord-346104-18x8u2oe	2019	Herpesvirus infection in the bear tissues and tissue cultures were detected by PCR using degenerate primers specific to the DNA polymerase gene (DPOL) and glycoprotein B gene (gB). To determine whether the observed viral particles are herpesviruses, tissues collected from the two NV black bears B1 and B2 were examined by nested PCR using panherpesvirus primers (Pozo et al., 2016 ) and herpesvirus consensus primers (VanDevanter et al., 1996) . To determine how common this UrHV-1 like virus is in black bear population, various tissues from 15 bears collected from Nevada, California, and Oregon were analyzed by this hybrid nested PCR with panherpesvirus primers in primary reaction and UrHV-1specific primers in the secondary reactions. Positive amplification with UrHV-1 specific primers was observed in total DNA of white blood cells (WBC) from two black bears from Nevada and one from Oregon.
cord-346264-hnwgzt6v	2020	Although GIII Cowden strain replicated in the villous epithelial cells and caused intestinal lesions in the proximal small intestines (mainly in duodenal and less in jejunum), leading to mild to severe diarrhea, in the orally inoculated neonatal gnotobiotic pigs, the significance of porcine SaVs in different ages of pigs with diarrhea in the field is still undetermined. The first porcine sapovirus (SaV), the Cowden strain was discovered by electron microscopy in the intestinal contents of a 27-day-old diarrheic nursing pig in the United State in 1980 (Saif et al., 1980 . In this review, we will summarize current knowledge on the pathogenesis of GIII Cowden strain, the epidemiology and genetic diversity of porcine SaVs, and the diagnosis of SaV infection in pigs. It may also explain why porcine SaV Cowden strain did not replicate in other organs when piglets were inoculated intravenously (IV) with the virus (Guo et al., 2001) .
cord-347270-x05tfkgx	2017	
cord-347924-w06ho8sn	2007	In this study, we tried to identify dengue virus-specific CD4(+) T-cell epitopes, which can induce PBMC (peripheral blood mononuclear cells) isolated from DF convalescent patients (dengue virus type 1 infection) to secrete IFN-γ. Currently, many studies suggested that dengue-specific T-cell immune response are hypothesized to play an important role in the immunopathogenesis of DHF during a secondary DEN virus infection, and induction of immunopathology by T lymphocytes may occur by various mechanisms, including cell-mediated cytotoxicity and/or cytokine production (Miskovsky et al., 1994; Vergelli et al., 1997) . In the present study, a combination of bioinformatics tools (epitope-prediction programs RANKpep) and in vitro assays (enzyme-linked immunospot assay (ELISPOT) and intracel-lular cytokine staining assay (ICS)) was used to screen and select antigen sequences as potential DEN-specific CD4 + T-cell epitopes, then the selected sequences are tested for biological function by their activation of T cells of DEN infected populations.
cord-351766-ik89889i	2020	It is well-known that melatonin as an anti-oxidative and anti-inflammatory agent counters acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) induced by viral and bacterial infections. In addition to mentioned viral infectious diseases, melatonin has been shown to play therapeutic roles in infection induced by Ebola virus. The Ebola virus increases blood coagulation, weakens the immune system, and mediates noticeable inflammatory responses leading to the oxidative stress-induced organ and cellular damages. (2020) Beside oxidative cell injury induced by SARS-CoV-2, serum inflammatory markers such as D-dimers, C-reactive protein, and ferritin, neutrophil count in a complete blood count (CBC), and inflammatory cytokines, and chemokines increase in severe COVID-19 patients (Merad and Martin, 2020a; Ruan et al., 2020) . Clinical study of mesenchymal stem cell treating acute respiratory distress syndrome induced by epidemic Influenza A (H7N9) infection, a hint for COVID-19 treatment Inhibitory effect of melatonin on lung oxidative stress induced by respiratory syncytial virus infection in mice