cord-003246-3ajfb18m	2018	Previous studies have shown that lung injury in patients with HFMD is associated with neurogenic pulmonary edema (NPE) after EV71 infection of the brainstem, rather than with direct viral invasion (Jiang et al. Protein edema in the alveolar space with fibrin exudation was observed inside, and some alveoli were filled with mononuclear cells, alveolar macrophages, exfoliated epithelial cells and cell debris (G); the alveolar septum was widened, the capillaries in the septum were highly dilated and congested, with infiltration of inflammatory cells (H); intrapulmonary bronchitis and bronchiolitis, diffuse or focal infiltration of inflammatory cells in the wall and surrounding tissues (I, J); compensatory emphysema phenomenon of ruptured alveolar wall and fusion of pulmonary alveoli (K); the lymph nodes near the hilar bronchus indicated a reactive hyperplasia, germinal center enlargement, paracortical zone atrophy, and lymphocyte depletion (L) (black arrow). Lung tissues of EV71 infected patients with severe HFMD showed interstitial pneumonia and positive viral antigens in the pulmonary epithelial cells and macrophages.
cord-005340-o7tkxs3s	2016	Confronted with this imported case, the government in China has implemented surveillance, monitoring, and other measures to prevent the spread of RVF in China (http://www. Based on the lessons learned during the outbreaks in Saudi Arabia and Yemen, and given these conditions, there is a high risk that the imported case may spread or even cause an outbreak, if proper measures to prevent and control RVF are not implemented. Early detection of suspected cases is the key to ensure that timely control measures are implemented to prevent the spread and outbreak of emerging or re-emerging infectious diseases, such as Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Ebola, as well as RVF . Meanwhile, the effectiveness of strengthening collaboration and coordination across sectors, such as government, the Centers for Disease Control and Prevention, researchers, and hospitals, to make prevention and control measures more efficient, was demonstrated when the MERS case was imported in China (Su et al., 2015; Su et al., 2016b) and during the RVF outbreak in Saudi Arabia (Himeidan et al., 2014) .
cord-005372-7x8ro8p2	2014	PRDC is caused by a combination of viral and bacterial agents, such as porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), Mycoplasma hyopneumoniae (Myh), Actinobacillus pleuropneumoniae (APP), Pasteurella multocida and Porcine circovirus 2 (PCV2). Our findings indicate that positive farms have increased risk of PRDC presentation, in particular, PCV2, APP and Myh. Swine infl uenza is an acute, highly contagious respiratory disease resulting from infection with type A infl uenza virus, a member of the Orthomyxoviridae family. PRDC results from a combination of viral and bacterial agents, including porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), Mycoplasma hyopneumoniae (Myh), Actinobacillus pleuropneumoniae (APP), Pasteurella multocida and porcine circovirus type 2 (PCV2) (Kim J, et al., 2003) . The main goal of the current research was to generate surveillance, epidemiological, antigenic as well as phylogenetic data to ascertain the presence of swine influenza (H1N1) pandemic virus and determine its association with PRDC (PRRSV, Myh, APP and PCV2) in sows from production farms in Colombia.
cord-005397-i7x50taa	2012	To provide a foundation for the development of rapid and specific methods for the diagnosis of rabies virus infection, anti-rabies virus monoclonal antibodies were prepared and rabies virus nucleoprotein and human rabies virus vaccine strain (PV strain) were used as immunogens to immunize 6–8 week old female BALB/c mice. Spleen cells and SP2/0 myeloma cells were fused according to conventional methods: the monoclonal cell strains obtained were selected using the indirect immunofluorescence test; this was followed by preparation of monoclonal antibody ascitic fluid; and finally, systematic identification of subclass, specificity and sensitivity was carried out. Two high potency and specific monoclonal antibodies against rabies virus were obtained and named 3B12 and 4A12, with ascitic fluid titers of 1:8000 and 1:10000, respectively. Thus, the preparation of potent and specific monoclonal antibodies against rabies virus will contribute significantly to development of techniques for laboratory diagnosis of rabies.
cord-006752-fmdvwnbw	2014	While there are other potential explanations for this large number of human infections with an avian influenza virus, we investigated whether a lack of conserved T-cell epitopes between endemic H1N1 and H3N2 influenza viruses and the novel H7N9 virus contributes to this observation. In the 2009 H1N1 pandemic (pdmH1N1) outbreak, we analyzed the conserved CD8 T cell epitopes in pdmH1N1 virus, and demonstrated that the conserved epitope-specifi c T cells established by seasonal infl uenza virus could cross react against the pandemic virus, which might contribute to the milder pandemic H1N1 illness overall and the lower infection attack rate in young adults even though they did not have detectable cross-neutralizing antibody (Tu W, et al., 2010) . Like avian H5N1 infection, most of patients with H7N9 infection who were hospitalized for medical care had severe illness, although both of the two viruses had conserved T cell epitopes that are shared with seasonal infl uenza virus.
cord-014920-mmykzj9w	2008	The X protein (HBx) of Human hepatitis B virus (HBV) acts as an indirect transcriptional transactivator to regulate the expression of many viral and cellular genes, as well as playing a critical role in pathogenesis and the development of Hepatocellular carcinoma (HCC). In addition, the viral X region appears to have pleiotropic effects that could also be involved in the oncogenic processes, including transcriptional activation of cellular growth regulatory genes, modulation of apoptosis and inhibition of nucleotide excision repair of damaged cellular DNA (8, 14, 16) . Many human hepatocellular carcinomas contain integrated HBV, and the viral X protein appears to have pleiotropic effects that could be involved in the oncogenic process. Putative tumor suppressor YueF affects the functions of hepatitis B virus X protein in hepatoma cell apoptosis and p53 expression The hepatitis B virus X protein promotes tumor cell invasion by inducing membrane-type matrix metalloproteinase-1 and cyclooxygenase-2 expression
cord-014923-gfiqjgxg	2009	It has been established that the S protein in this pathogen plays an important rule in the adsorption and penetration of SARS-CoV into the host cell by interaction with the ACE2 receptor. To determinant which functional motif of the S protein was involved in the interaction with ACE2, seven truncated S proteins deleted from the N or C terminal were obtained by an E.coli expression system and purified by column chromatography to homogeneity. The adsorption were quantified by ELISA, and the results indicated that amino acids from 388 to 496 of the S protein was responsible for the interaction with the ACE2 receptor, and the interaction could be completely disrupted by an antibody specific to these amino acids. Our results showed that S1-1, S1-2, S1-3, S1-5 and S1-7 can interact with purified ACE2 protein specifically, but S1-4 and S1-6 cannot interact with this receptor. Inactivated SARS-CoV vaccine elicits high titers of spike protein specific antibodies that block receptor binding and virus entry
cord-014927-g4r7j8hk	2008	Since then, the government has been increasing investment in science and technology with major emphasis on both infectious diseases control and new drug research and development. For the first time, development of 100 new drugs and control of major infectious diseases (AIDS, HBV, TB and other emerging infectious diseases) have been selected as national key scientific projects. The epidemic in China began at the end of the 1980s, when IDUs in Ruili, a small town bordering Myanmar in Yunnan province, were found to be infected by HIV. By the mid 1990s, the HIV/AIDS epidemic was scaled-up by both further spread of drug abuse in other regions and blood contamination in the illegal plasma collection activities in central China (13, 14) . HIV infected people were first identified in Intravenous drug users in China Control of transmission of HIV among drug users and commercial blood donors
cord-014932-web2tdef	2009	The structure genes spike (S), nucleocapsid (N), membrane (M), small membrane (sM) of a porcine epidemic diarrhea virus (PEDV) strain DX isolated in Gansu province, North-west of China, were cloned, sequenced and compared with published sequences of PEDV strains. The N gene was cloned using two primers which contained Nco I and BamH I restriction enzyme sites and subcloned into expression vector pET30a. Cloning and sequence analysis of the N gene of porcine epidemic diarrhea virus LJB/03 Cloning and sequence analysis of the N gene of porcine epidemic diarrhea virus LJB/03 Cloning and sequence analysis of the Korean strain of spike gene of Porcine epidemic diarrhea virus and expression of its neutralizing epitope in plants Cloning and Sequence Analysis of the Nucleocapsid Gene of Porcine Epidemic Diarrhea Virus Chinju99 Cloning and sequence analysis of the spike gene of Porcine epidemic diarrhea virus Chiju99
cord-014938-7evmiuv5	2008	title: Expression of prothrombinase/fibroleukin gene fg12 in lung impairment in a murine severe acute respiratory syndrome model To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) through trachea was established. In a separate experiment, tissues including lungs, spleen, liver, kidneys, intestine, heart, brain were collected at a series of time points from Balb/cJ mice infected with MHV-3 through trachea. Detection of severe acute respiratory syndrome-associated coronavirus in pneumocytes of the lung The clinical pathology of severe acute respiratory syndrome (SARS): a report from China Lung pathology of severe acute respiratory syndrome (SARS): a study of 8 autopsy cases from Singapore Discovery of novel human and animal cells infected by the severe acute respiratory syndrome coronavirus by replication-specific multiplex reverse transcription-PCR A novel coronavirus associated with severe acute respiratory syndrome
cord-014946-l3vwb2v7	2009	title: Genetic variation analyses of nsp2 gene of PRRSV in Ningxia Hui Autonomous Region of China To gain a better understanding of the genetic diversity and evolution of PRRSV in the Ningxia Hui Nationality Autonomous Region (Ningxia) of China, the nsp2 genes from a series of PRRSV strains collected from the region in 2007 were partially sequenced. Comparison of the nucleotide sequence with ch-1a indicated that nsp2 genes of seventeen Ningxia isolates (NX strain) have deletions of 87 nucleotides. The nsp2 genes of the seventeen isolates had 74.9%–100% nucleotide sequence identities with each other. The amplified PCR products were analyzed by agarose gel electrophoresis and purified using the QIAquick gel extraction kit (Qiagen) per the manufacturer''s protocol. All nucleotide sequences were obtained from clinical sample RNA by direct sequencing of PCR products. The nsp2 genes of seventeen isolates had 74.9%-100% nucleotide sequence identity with each other (Fig.3) .
cord-025181-eg108wcd	2020	In this study, with biologically cloned viruses from a single clinical isolate, we have established two mouse models of DENV infection, one is severe lethal infection in immunocompromised mice, and the other resembles self-limited disease manifestations in Balb/c mice with transient blockage of type I IFN responses. Further, we compared the infectivity of these two viral variants in a self-limited infection model, in which type I IFN receptor of wild-type Balb/c mice had been transiently blocked before infection, and found only the virus strain exhibiting larger plaque size caused infectious viral particles in sera. We have recently developed a ZIKV infection model in Balb/c mice with transient blockage of type I IFN Fig. 2 Phylogenetic analysis of DENV-2 1D4-5-SP and DENV-2 8H2-7-LP with representative serotype-2 dengue viruses of different genotypes isolated from different geographical regions.
cord-025232-5itrsfmk	2020	The strategy of using a clinically approved and replication-defective HAdV-5 vector provides a novel approach to develop universal adenovirus vaccine candidates against all the other types of adenoviruses causing ARDs and perhaps other adenovirus-associated diseases. In this study, the commercially-available and gene therapy use approved replication-defective HAdV-5 vector was used to construct a recombinant attenuated human adenovirus type 3 vaccine (Ginn et al. The complete hexon gene of HAdV-3 GZ01 was cloned into the AdEasy TM Adenoviral Vector, and this type-specific antigen was expressed when the recombinant adenovirus vaccine was inoculated into mice. The recombinant vaccine is expected to be used in the prevention of ARD outbreaks caused by HAdV-3 infections, and to serve as a model using adenovirus vectors for the construction of other vaccines against additional important serotypes of adenoviral respiratory pathogens. Mice were either inoculated with HAdV-3 wild-type strain GZ01 or immunized with the rAd3H recombinant vaccine by either the intranasal route or intramuscular route, respectively, to assess the antibody titer.
cord-033952-b9fxqnni	2020	Hantaviruses cause two clinical syndromes in humans; designated hemorrhagic fever with renal syndrome (HFRS), and hantavirus cardiopulmonary syndrome (HPS). However, the cases of women infected with hantavirus during pregnancy are rarely reported even in areas where hantaviruses are concentrated, which poses certain difficulties for subsequent research and clinical management. (1999) reviewed five cases of HPS during pregnancy, and as expected, there was no evidence of vertical transmission, though SNV infections mostly had severe consequences, even death, in pregnant women and fetuses. Although there are not many cases of hantavirus infection reported in pregnant women, even in the endemic areas, clinicians are expected to thoroughly consider severe consequences when they receive patients with similar symptoms. Hemorrhagic fever with renal syndrome caused by Hantaan virus infection in four pregnant Chinese women Clinical analysis of 21 cases of hemorrhagic fever with pregnancy renal syndrome Clinical analysis of 21 cases of hemorrhagic fever with pregnancy renal syndrome
cord-259443-5sv3dwbs	2016	title: Risk factors for severity and mortality in patients with MERS-CoV: Analysis of publicly available data from Saudi Arabia Initially, only limited information such as patients'' age, sex, nationality, address, date of diagnosis, presenting symptoms, and presence of any pre-existing condition were made publicly available; however, since 24 th September 2014, additional information on likely exposure to animals and other suspected MERS cases were added, and it was recorded whether the exposure likely occurred at health care settings or in community settings. In our study, presence of a respiratory disease was not a significant risk factor and we did not explore the association of older age with mortality, because essentially all patients aged ≥ 65 years in our cohort had a pre-existing disease, but age itself could be an independent risk factor, as other studies from Saudi Arabia and South Korea demonstrated that age > 60 years (in some studies ≥ 65 years) was significantly associated with mortality (Feikin et al., 2015; Majumder et al., 2015; Saad et al., 2014) .
cord-261415-qxl14j2m	2020	In addition, given that uncontrolled pulmonary inflammation is likely a leading cause of fatality in SARS-CoV-2 infection, we also attempt to speculate possible therapeutic interventions that may be applied to attenuate inflammatory responses in order to reduce mortality (Fig. 2) . In SARS-CoV infection, viroporin 3a has also been shown to trigger the activation of NLRP3 (NOD-like receptor protein 3) inflammasome and the secretion of IL-1b in bone marrowderived macrophages, suggesting the induction of cell pyroptosis , which can cause the release of large amounts of proinflammatory factors (Fink and Cookson 2005) . However, previous studies in animal models have shown that in SARS-CoV infection, such anti-S protein-neutralizing antibodies (anti-S-IgG) can also cause severe lung injury by altering inflammatory responses (Liu et al. This animal study suggests that despite viral suppression, the presence of anti-spike protein antibody at the acute stage of SARS-CoV infection can actually cause severe acute lung injury that persists until the late stages.
cord-269021-juh2qkm0	2020	Human beings have experienced a serious public health event as the new pneumonia (COVID-19), caused by the severe acute respiratory syndrome coronavirus has killed more than 3000 people in China, most of them elderly or people with underlying chronic diseases or immunosuppressed states. In the case of a gradually improved infectious disease surveillance system, the research on forecasting and early warning of epidemics based on models has become the focus of the public health system. In response to the current epidemic of SARS-CoV-2, many researchers have developed mathematical models with varying degrees of complexity, aiming to assess the capacity of pathogen transmission and which interventions are most likely to be effective (Fig. 2) . Estimating the unreported number of novel coronavirus (2019-nCoV) cases in China in the first half of January 2020: a data-driven Modelling analysis of the early outbreak
cord-273373-5elel6qo	2016	The CoV proteases, which play pivotal roles in viral gene expression and replication through a highly complex cascade involving the proteolytic processing of replicase polyproteins, are attractive targets for drug design. Structural analyses revealed that the substrate-binding pockets of various CoV M pro s are highly conserved, which led to the concept of "widespectrum inhibitors" for targeting all CoVs. Through a structure-based drug design, we have identified a lead compound named N3 with potent inhibitory activity against all M pro s tested ( Figure 2D) . Structurebased design, synthesis, and biological evaluation of a series of novel and reversible inhibitors for the severe acute respiratory syndrome-coronavirus papain-like protease Severe acute respiratory syndrome coronavirus papain-like novel protease inhibitors: design, synthesis, protein-ligand X-ray structure and biological evaluation Papain-like protease 2 (PLP2) from severe acute respiratory syndrome coronavirus (SARS-CoV): expression, purification, characterization, and inhibition
cord-273608-dxx3p1x5	2013	Total nucleic acids were extracted using the EZ1 system (Qiagen, Germany) and 17 respiratory viruses and genotypes including influenza A virus (FluA), FluB, parainfluenza virus 1 (PIV1), PIV2, PIV3, PIV4, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), rhinoviruses (RhV), enteroviruses (EnV), human bocaviruses (hBoV), adenoviruses (AdV), four coronaviruses (229E, OC43, NL63 and HKU1), and FluA 2009 pandemic H1N1(H1N1-p) were detected and identified by the ResPlex II kit. In this study, we evaluated the ResPlex II V2.0 kit (Qiagen, Germany), which uses a target enriched multiplexing RT-PCR amplification coupled with a suspension array detection, for detection and identification of a panel of respiratory specimens in pediatric inpatients with LRTIs. Clinical accuracy of the ResPlex II assay was validated on a panel of prospectively collected consecutive nasopharyngeal swab (NPS) specimens in comparison to viral culture and a monoplex real-time TaqMan RT-PCR.
cord-273712-r2akpce8	2016	In the same beta group, the receptors for mouse hepatitis virus (MHV) and bovine coronavirus (BCoV) are carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and a sugar, respectively, despite their high sequence homology Peng et al., 2012) . In our study, we compared the efficiency of pseudotyped viruses with S proteins from different groups of CoVs. Furthermore, the cell tropisms of TGEV and PEDV were characterized by live and pseudotyped viruses. Therefore, we compared the S protein amino acid sequences of CoVs from different groups, including SARS-CoV, MHV, HCoV-229E, TGEV, PEDV, HCoV-OC43, BCoV, and IBV (Gen-Bank accession numbers ABD72982.1, AAR92025.1, NP_073551.1, ABG89335.1, NP_598310.1, AAT84362.1, ABM66810.1, and NP_040831.1, respectively) using ClustalW ( Figure 1B ). Lentiviruses pseudotyped with SARS-CoV S protein could efficiently infect 293T cells expressing ACE2, and the pseudovirus level after entry reached 10 6 relative light units (RLU) ( Figure 2B ). To further study the cellular entry of CoVs, we used live PEDV and TGEV to infect different cell lines.
cord-274785-9jgg8ukr	2019	TIA/G3BP/PABP-specific stress granules (SG) and GW182/DCP-specific RNA processing bodies (PB) are two major distinguishable RNA granules in somatic cells and contain various ribosomal subunits, translation factors, scaffold proteins, RNA-binding proteins, RNA decay enzymes and helicases to exclude mRNAs from the cellular active translational pool. The process of SG formation can be artificially divided into the following steps ( Fig. 2) : (1) accumulation of stalled translation initiation complexes ) in response to various types of stress; (2) the RNA-binding proteins such as RAS-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) and T cell-restricted intracellular antigen 1 (TIA1) bind mRNAs and aggregate to nucleate SG formation. SG proteins (eIF4G, eIF3, PABP) are selectively sequestered within Ebola virus inclusion bodies and co-localize with viral RNA to form inclusion body-bound granules, which are functionally and structurally different from canonical SG, probably leading to inhibit the antiviral role of SG (Nelson et al. 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-284549-edliu3it	2019	In this study, we screened all the nonstructural proteins of HCV and found that HCV NS2 could suppress RNAi induced either by small hairpin RNAs (shRNAs) or small interfering RNAs (siRNAs) in mammalian cells. In this study, we uncovered that HCV nonstructural NS2 protein possessed a potent in vitro VSR activity that suppressed the RNAi induced by short hairpin RNA (shRNA) and siRNA in mammalian cells. Our results showed that the reversal effect of EGFP silencing could be observed at 48 hpt (Fig. 2C) , indicating that the VSR activity was dependent on the expression level of HCV NS2 protein. To investigate whether HCV NS2 can inhibit this step, small RNAs harvested from HEK293T cells co-expressing EGFP-specific shRNA together with NS2 were subjected to Northern blotting with a DIG-labeled RNA probe targeting EGFP siRNA produced from shRNA by Dicer.
cord-295640-mhfu0e9r	2019	Therefore, the cross-protection potentially correlates with both NP and M2e-specific humoral and cellular immune responses induced by RVJ-4M2eNP, which expresses a fusion antigen of full-length NP preceded by four M2e repeats. Previously, we expressed a fusion protein of NP and M2e (NM2e) in Escherichia coli and showed that immunization with NM2e formulated with aluminum hydroxide gel protected mice from a lethal challenge with heterologous influenza virus . BALB/c mice were immunized with the recombinant viruses to measure NP-and M2e-specific humoral and cellular immune responses as well as protective effect against lethal challenge with a heterologous influenza virus. Mice immunized with the recombinant vaccinia virus RVJ-NPM2e and RVJ-M2eNP showed strong antibody responses against NP, with lower titers of antibodies against M2e (Fig. 3A) . The recombinant vaccinia virus expressing 4M2e and full-length NP fusion antigen induced strong cross-protection (92%) against a lethal heterosubtypic PR8 challenge at 20 MLD 50 and thus regarded as the optimal one among the four constructs.
cord-298734-h286m32c	2020	title: Long Term Culture of Human Kidney Proximal Tubule Epithelial Cells Maintains Lineage Functions and Serves as an Ex vivo Model for Coronavirus Associated Kidney Injury In this study, we successfully established long term cultures of normal human kidney proximal tubule epithelial cells (KPTECs) in 2D and 3D culture systems using conditional reprogramming (CR) and organoids techniques. Due to the lack of specific detection of ACE2 mRNA and protein expression in human kidney tubule cells, it is hard to confirm the direct infection of SARS-CoV-2. In this study, we firstly established long term cell cultures of KPTECs using 2D CR and 3D organoids technologies, which maintained the lineage function, and the ability to differentiate and repair DNA damage. In terms of the questions above, we need model systems to study infection of SARS-CoVs in ACE2 expressing cell types, especially in kidney epithelial cells (Hamming et al.
cord-300466-sk9iilum	2020	According to the Chinese Centers for Disease Prevention and Control (CDC) report, among 72,314 COVID-19 cases in China''s mainland most of cases (81%) presented only mild illness or moderate pneumonia, yet 14% developed severe symptoms such as dyspnea, high respiratory frequency and low blood oxygen saturation, and another 5% were in critical conditions like respiratory failure, septic shock, and multiple organ dysfunction/failure (Epidemiology Working Group for NCIP Epidemic Response and Chinese CDC, 2020; Wu and McGoogan 2020) . In this study, we, compared the results of serologic tests and nucleic acid test (NAT) from a group of COVID-19 patients in Wuhan, and analyzed the serologic IgM and IgG antibody level of patients with different disease severity. In summary, this study supported the combination of serologic testing and NAT in routine COVID-19 diagnosis and provided evidence on the temporal profile of antibody response against SARS-CoV-2 in patients with different disease severity.
cord-312080-pu6m4qad	2016	This review focuses on the recent progress of human virological research with 3D cell culture models, including human viral growth, replication, proliferation, infection, viral life cycle, virus-host interaction and the development of antiviral drugs. A multitude of research has shown that RWV-derived models utilizing human cells are a valuable tool for investigating viral growth, replication, viral infection, viral entry, the viability of virions and virus-host interaction (Margolis et al., 1997; Long et al., 1998; Nickerson et al., 2007; Straub et al., 2007; Barrila et al., 2010; Berto et al., 2013; Goodwin et al., 2015) . As keratinocytes are the main target cells for productive infection in vivo for VZV, characterization of viral replication in organotypic raft cultures of these cells represents a very relevant model for studying virus-host cell interactions and antiviral agents (Andrei et al., 2005) .
cord-315486-pjb5v1tc	2020	As expected, COVID-19 patients with health conditions like hypertension or diabetes had a longer length of hospital stay than those without, but this was at the limit of statistical significance (Fig. 1A , P = 0.07). These findings confirmed an increased disease severity in COVID-19 patients with hypertension or diabetes (Liu et al. SARS-CoV-2 infections lead to a fast activation of innate immune cells, especially in COVID-19 patients developing severe disease . These results suggest different mechanisms exist for hypertension or diabetes as risk factors for severe cases of COVID-19. Despite these limitations, we were able to identify different laboratory abnormalities on admission in COVID-19 patients with hypertension or diabetes, which might shed light on future mechanistic studies. Are patients with hypertension and diabetes mellitus at increased risk for covid-19 infection? Risk factors associated with disease severity and length of hospital stay in covid-19 patients
cord-319501-a2x1hvkk	2016	Particularly, the host pathogen recognition receptors and the signal transduction pathways to mount an effective antiviral response against SARS and MERS coronavirus infection are discussed. This suggests SARS-CoV N may interfere with RNA recognition by host immune sensors such as RIG-I and MDA5 thus achieving suppressive role in IFN production. Our group demonstrated that MERS-CoV ORF4a interacts with PACT, a cellular dsRNA-binding protein that optimally activates RIG-Iand MDA5-induced type I IFN production, in an RNAdependent manner (Siu et al., 2014c) . Infection with SARS-CoV and MERS-CoV has been accompanied with suppression of innate immune response, most notably with the suppression of type I IFN production and signaling pathways. Severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type I interferon, in infected cells Middle East respiratory syndrome coronavirus 4a protein is a double-stranded RNA-binding protein that suppresses pact-induced activation of RIG-I and MDA5 in the innate antiviral response
cord-322005-70snojec	2020	title: Isolation and Growth Characteristics of SARS-CoV-2 in Vero Cell In a recent report, 149 mutations were found among 103 sequenced isolates of SARS-CoV-2 . To investigate whether our viruses show mutations different from other reported SARS-CoV-2, all the seven isolates were sequenced at the 3rd passage and the sequences were aligned with coding sequence (CDS) of SARS-CoV-2 Wuhan-Hu-1 (NC_045512). It is interesting to note that these seven patients infected with SARS-CoV-2 have high viral load in the early stage of clinical sign, which is consistent with previous reports (Kim et al. A The cytopathic effect was observed in Vero cells infected with the isolated viruses at 5 dpi. In conclusion, seven SARS-CoV-2 strains were isolated, sequenced and characterized in Vero cells, and a deletion mutation was identified after short passage in Vero cells. Viral load kinetics of SARS-CoV-2 infection in first two patients in Korea SARS-CoV-2 viral load in upper respiratory specimens of infected patients
cord-322166-ajolu2rh	2013	The ability of H5N1 to cross species boundaries, and the presence of polymorphisms that enhance virulence, present challenges to developing clear strategies to prevent the pandemic spread of this highly pathogenic avian influenza (HPAI) virus. Disrupted cytokine and chemokine expression, especially IFNs and TNF, and decreased antiviral activity of innate immune response mediators, such as protein kinase resource and retinoic acid-inducible gene product I (RIG-I), directly lead to increased virulence of the virus (Haye K, et al., 2009; Jackson D, et al., 2008; Lipatov A S, et al., 2005; Munir M, et al., 2011) . Thus, patients with H5N1 disease typically present with a hyper-induced systemic inflammatory response syndrome and a higher and a more prolonged viral load in respiratory specimens than other seasonal influenza virus like human H1N1 viruses (Chan M C, et al., 2005; Kuiken T, et al., 2010; Lee D C, et al., 2012; Peiris J S, et al., 2010; Sandbulte M R, et al., 2008) .
cord-329876-4cgrjnjo	2016	title: Structural and mutational analysis of the interaction between the Middle-East respiratory syndrome coronavirus (MERS-CoV) papain-like protease and human ubiquitin To contribute to an understanding of this process, we present here the X-ray crystal structure of a complex between MERS-CoV PL(pro) and human ubiquitin (Ub) that is devoid of any covalent linkage between the two proteins. The substrate-binding site of MERS-CoV PL pro features significant differences from those of the corresponding SARS-CoV enzyme and human ubiquitin-specific proteases (USPs, such as, USP14) (Hu et al., 2005; Chou et al., 2014; Ratia et al., 2014) . Hence, we crystallized the ubiquitin (Ub) complex of a MERS-CoV PL pro variant that had the active-site Cys111 replaced by serine (C111S) and determined the structure at 3.16 Å ( Figure 1A ). Crystal structure of the Middle East respiratory syndrome coronavirus (MERS-CoV) papain-like protease bound to ubiquitin facilitates targeted disruption of deubiquitinating activity to demonstrate its role in innate immune suppression
cord-332672-fbwz8oxp	2013	It was suggested that the previously known bat SL-CoV stains cannot jump from bats to civets or humans owing to the significant differences between their RBDs (Li F, 2013); 2) although SL-CoVs have been identified from different bat species, isolation of a live SL-CoVs from bats never succeed; 3) no native SL-CoV from bats could use ACE2 as receptors and infect human cells, only when its RBD is replaced with the counterpart from a human SARS-CoV strain (Li W, et al, 2003; Becker M M, et al, 2008; Ren W, et al, 2008) . The residue 479 is known to be an asparagine only in human SAR-CoVs, but not in the previously identified bat SL-CoVs or civet SAR-CoVs. It is proposed that an asparagine at position 479 has a higher binding affinity with human ACE2 and is likely to determine whether the virus can infect humans (Li F, 2013) .
cord-332861-7b5pzmk6	2020	title: Clinical Features and Treatment of 2019-nCov Pneumonia Patients in Wuhan: Report of A Couple Cases Considering the cause was unknown, we also used drugs to treat atypical pathogens, including moxifloxacin for mycoplasma and chlamydia, and oseltamivir and abidol hydrochloride for influenza A virus; meanwhile, the patient was given Chinese patent medicine Tanreqing iv gtt for adjunctive therapy. We also used drugs to treat atypical pathogens, including moxifloxacin for mycoplasma and chlamydia, and oseltamivir and abidol hydrochloride for influenza A virus; meanwhile, the patient was given Chinese patent medicine Tanreqing iv gtt for adjunctive therapy. On admission, beside fever, the male was predominately manifested by dyspnea and only had mild abnormality in routine urine and stool test results, while the female had obvious gastrointestinal symptoms such as vomiting and diarrhea. In this study, the male had a more severe decrease in immune cells and more severe conditions than the female.
cord-333195-m4gvpsf8	2020	title: Development of a Novel Reverse Transcription Loop-Mediated Isothermal Amplification Method for Rapid Detection of SARS-CoV-2 Here, we present a novel visual reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for rapid and sensitive detection of SARS-CoV-2 using mismatch-tolerant technique. The RdRp primers showed higher amplification efficiency, and were selected to establish the SARS-CoV-2 detection assay using the mismatch-tolerant RT-LAMP method Zhou et al. For the POCT diagnosis of SARS-CoV-2 infection in the resource-poor settings, we developed the assay into a visual detection using WarmStart Colorimetric LAMP 2 9 Master Mix (New England Biolabs, Beverly, MA, United States). The sensitivity of the colorimetric RT-LAMP assay for SARS-CoV-2 was 30 copies per reaction, slightly lower than the real-time monitoring (Fig. 1E) . The evaluation with 24 clinical samples showed that all 17 COVID-19 patients in Nantong city were positive for SARS-CoV-2 by both the RT-LAMP and the RT-qPCR assays, showing a full consistence.
cord-338606-6nk2ij20	2019	Fulfilling this objective, virologists from fourteen countries in North America, Europe, Africa, Asia, and the Middle East met on 25–27th August 2019 in Stockholm, Sweden at the Karolinska University Hospital for the first Committee Meeting of WSV. The World Society for Virology (WSV) was founded in 6 May 2017 and incorporated on 14 December 2017 as a non-profit organization, in the state of Massachusetts in the United States of America. WSV also collaborates with other international organizations and virology societies (Abdel-Moneim et al. The first committee meeting of the WSV was supported by the Swedish Research Council and organized at the Karolinska University Hospital (KUH), Stockholm, Sweden from 25 to 27th August 2019. In the scientific session, there was a series of presentations on different topics of virology: Following these two presentations, a series of sessions concerning the future plans for WSV were conducted. The First Committee Meeting of the World Society for Virology
cord-348467-a2e3f161	2016	Most departing pilgrims (62%) were aware of a mod-erate to high infection risk from raw camel milk consumption, yet 21% of participants were willing to drink it. Nevertheless, among those who were aware of MERS-CoV, 27% did not fully realize the risk of catching the disease from unpasteurized camel milk, 15% were willing to drink raw camel milk, and 23% were keen to visit camel farm in Saudi Arabia (Table 3) . A unique finding to emerge from our study was that departing pilgrims with knowledge about MERS-CoV were significantly more aware of the risk of drinking raw camel milk (43% vs. Therefore, pilgrims who consume raw milk or other products are at risk of other zoonotic diseases if not MERS-CoV, and therefore, could benefit from appropriate health education.
cord-352988-9ey3ir5e	2010	A polyphenolic compound, 1,2,4,6-tetra-O-galloyl-β-D-glucose (1246TGG), was isolated from the traditional Chinese medicine Phyllanthus emblica L. Results indicates that treatment with 1246TGG (6.25 μg/mL, 3.13 μg/mL), reduced both HBsAg and HBeAg levels in culture supernatant, yet the inhibitory effects tend to decline with the assay time. Here, we investigated the anti-HBV activity of 1246TGG by detecting the HBsAg and HBeAg secretion levels in HepG2.2.15 cell culture, a cell line derived by transfection of cloned HBV DNA into human hepatoblastoma cell line HepG2 and used to assay for anti-HBV agents [4] . To determine the inhibitory effects of 1246TGG on HBV antigen secretion, cells were treated with 1246TGG at concentrations of 6.25µg/mL and 3.13µg/mL every 3 d during the 10 d treatment period. A cell culture assay for compounds which inhibit hepatitis B virus replication
cord-354529-k8p2u7iq	2020	Clinical information of patients was collected from the electronic medical information system of Jinyintan Hospital, including the following factors: demographic data; date of symptom onset, admission, first CP infusion and discharge; laboratory data before and after infusion of CP, including white blood cell count, neutrophil count, lymphocyte count, liver and kidney function test, and inflammatory factors such as high sensitive C-reaction protein (HsCRP); results of SARS-CoV-2 test and cycle threshold value (Ct value) of quantitative reverse transcription-polymerase chain reaction; patients'' status and treatments before or after the CP therapy, including the vital signs, anti-virus therapy, oxygen therapy, and other treatments; total volume dose of CP; pulmonary imaging examination data; information on complications such as transfusion-related adverse reactions. Clinical Benefit and Outcome of Patients with Prolonged Positivity of SARS-CoV-2 RNA after CP Therapy As shown in Table 3 , the median and interquartile ranged total volume of CP transfusion was 400 (200-400) mL in EN group and 400 (400-800) mL in LN group.
cord-356154-ifb3qiz7	2020	CT scan results in early February indicated lesions in bilateral lungs (Supplementary Table S1 ), but the result of the SARS-CoV-2 nucleic acid test was negative. However, the patient''s condition deteriorated again on February 20, and the nucleic acid test results were single positive for COVID-19 SARS-CoV-2. Notes: ND, no data; ?, positive; -, negative We assumed that HIV infection had damaged their immune systems; this could also explain why the patient tested negative for SARS-CoV-2 antibodies in the late stages of treatment when the disease became worse. In general, the blocking of the IL-6 receptor with tocilizumab has a particular effect on the treatment of COVID-19 patients with severe disease, but it may have little effect on patients with Fig. 1 The clinical courses of two cases co-infected with SARS-CoV-2 and HIV. COVID-19 patients with immunodeficiency disease may cause more severe illness and poor treatment response due to the destruction of the immune system.