cord-002026-wybmer7o	2010	We developed a high throughput screen to discover small molecule probes that inhibit virus infection of Vero E6 cells. Twenty-six compounds showed a dose response in the HT screen and were further evaluated in a time of addition assay and in a titer reduction assay. To confirm the activity and to test the cytotoxicity, the top 110 inhibitory compounds were evaluated in a dose response assay using the identical screen. All seven compounds screened in the time of addition experiment were confirmed to have anti-WNV activity based on the titer reduction assay and EC 90 values between 2.14~26.16 µM. None of the compounds showed anti-WNV activity as good as the positive control drug, MPA, however, the mechanism of MPA is not specific to the virus making the probes we identified of significant interest. The serially diluted compounds were also used for time of addition studies adding to the infected cells in 384-well plates at -1, 4, 8 and18 h post-infection with WNV (0.02 MOI).
cord-003070-6oca1mrm	2018	On the non-redundant benchmark test sets extracted from the PRIDB, the RPiRLS method outperformed RPI-Pred and IPMiner in terms of accuracy, specificity and sensitivity. The computational results showed that the RPiRLS classifier outperformed the RPiRLS-7G classifier in terms of various performance measurements, indicating that the diversity of amino acids at a sequence is important for the prediction of RPIs. The performance of predicting RPIs was evaluated by using 10-fold stratified cross-validation on the RPI2662 data set. For the RPI369 data set as shown in Table 4 , the performance of the RPiRLS method was 0.85, 0.92, 0.84 and 0.86 for predictive accuracy, AUC, specificity and sensitivity, respectively. The work presented here provided a computational method, called RPiRLS, to classify RNA-protein pairs as interacting or non-interacting by integrating a sequence-based derived kernel with regularized least squares.
cord-003297-fewy8y4a	2018	
cord-003329-zhauwxye	2011	Flexible docking and molecular dynamic simulations indicated that patchouli alcohol was bound to the neuraminidase protein of influenza virus, with an interaction energy of –40.38 kcal mol(–1). Therefore, the aim of the present study was to evaluate the anti-influenza A virus (H2N2) activity of patchouli alcohol by MTT assay and mouse influenza model. On such basis, explicitly solvated docking and molecular dynamic (MD) methods were applied to investigative the binding mode involving patchouli alcohol with influenza virus NA protein. Until now, it has been found that patchouli alcohol showed dose-dependent anti-influenza virus (A/PR/8/34, H1N1) activity, with an IC 50 value of 2.635 µM. As shown in Figure 2 , patchouli alcohol showed anti-influenza A (H2N2) virus activity in a timedependent manner. For pretreatment virus, Influenza A (H2N2) was incubated in medium containing patchouli alcohol for 1h at room temperature prior to infection of MDCK cells.
cord-003341-z5w56zeq	2013	Virtual screening of 300,000 compounds using Autodock 3 on the GVSS platform was conducted to identify novel inhibitors against the NS2B-NS3(pro). pastoris DENV4 NS2B-NS3 pro , fused to the α-factor secretion signal sequence and placed under the control of the methanol inducible alcohol oxidase promoter, was constructed to express the secreted protein in P. Thirty-six compounds were selected for in vitro assay based on their free energy binding (Table S1 ) and H-bonds interactions with amino acid residues at the NS3 pro active site. Among 300,000 compounds, 36 were selected for testing in vitro inhibitory activity against NS2B-NS3 pro based on hydrogen bond interactions [25, 36] . Activity of recombinant dengue 2 virus NS3 protease in the presence of a truncated NS2B co-factor, small peptide substrates, and inhibitors Novel dengue virus-specific NS2B/NS3 protease inhibitor, BP2109, discovered by a high-throughput screening assay
cord-003342-wmmbkmrg	2015	
cord-003344-rhld75dy	2015	Analogues or isosteres of α,γ-diketoacid (DKA) 1a show potent inhibition of hepatitis C virus (HCV) NS5B polymerase through chelation of the two magnesium ions at the active site. Hence, this paper also described a series of novel quercetin-3-O-benzoic acid esters (compounds 4, Figure 2 ) in an attempt to investigate whether the introduction of another carbonyl group at 3-position would result in an improved anti-HCV activity. The maintenance of anti-HCV activities for quercetin-3-O-benzoic acid-ester derivatives instead of the 3-O-aliphatic substituents revealed that the introduction of an electronegative carbonyl group at 3-O position could enhance the chelation ability between the inhibitor and metal ions, which contribute to the binding affinity in a similar way as the 3-hydroxyl group. To rationalize the observed activities of different substituents of quercetin and investigate the binding modes with NS5B, docking calculations were performed on the basis of the reported X-ray crystallographic structure of HCV genotype 1b RdRp complexed with uridine triphosphate (UTP) and divalent metal ions (PDB code: 1GX6 [22] ).
cord-003427-0dddrh4e	2015	title: Synthesis, Characterization, and Anti-Cancer Activity of Some New N′-(2-Oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones Derivatives The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2) and leukaemia (Jurkat), as well as in normal cell lines derived from human embryonic kidney (HEK293) using MTT assay. As a continuation to our previously reported data [49] [50] [51] , herein we designed eight isatin hydrazide-hydrazone derivatives, considering some of the factors responsible for such activity, including (i) the presence of isatin moiety; (ii) the presence of the hydrazide-hydrazone functionality; and (iii) valproic acid moiety ( Figure 1 ). All the prepared compounds were assessed against two different human tumour cell lines, including human liver (HepG2) and leukaemia (Jurkat), as well as in normal cell lines derived from human embryonic kidney (HEK293) using MTT assay. The presence of the valproic acid moiety as hydrazide-hydrazone derivatives 4a make the compound more targeted towards Jurakt cells in vitro.
cord-003539-tazd6dvm	2019	
cord-003990-15rg623y	2019	
cord-011969-bvun86eh	2020	
cord-012391-53hgrs40	2020	The fraction of 46 Br-p peptides isolated from burdock root with a molecular weight below 5000 Da and theoretic pI (isoelectric point) of 3.67–11.83 showed a narrow spectrum of activity against Gram-positive acne bacterial strains. To sum up: preliminary biological studies confirmed the anti-acne properties of the isolated peptide fraction from burdock root and pointed to the possibility of using it to create an active dressing on the skin. The burdock roots samples, isolated using ultrasound and salting out procedure, were fractionated using a Sephadex G-50 gel filtration (Materials and Methods, Section 4.1.) The obtained fractions were evaluated for the amount of protein and antibacterial properties (the diffusion test in solid medium). Br-f was initially tested for antibacterial activity (Figure 1, Table 1 ), and the remaining Br-f part was further ultrafiltrated in Amicon (10 kDa cut-off), followed by freeze-drying to obtain final Br-p peptide samples (the protein content was 51 µg/mL).
cord-012419-tmcm4kxn	2020	
cord-013364-pq9obtrc	2020	
cord-013366-sbdtpsz6	2020	
cord-013412-gj443yei	2020	The purpose of this review paper is to summarize the main approaches developed to date in the chemical and photodynamic inactivation of human and animal viruses using porphyrins and their analogues and to analyze and discuss the information on viral targets and antiviral activity of porphyrins, chlorins, of their conjugates with organic/inorganic compounds obtained in the last 10–15 years in order to identify the most promising areas. A cationic substituent is necessary to increase the solubility of porphyrins and their analogues in aqueous media, and three nitro groups provide linking of the gp120 protein with the glycoprotein ( Figure 3 ) and thereby inhibit fusion between the virus and the cell membrane. A cationic substituent is necessary to increase the solubility of porphyrins and their analogues in aqueous media, and three nitro groups provide linking of the gp120 protein with the glycoprotein ( Figure 3 ) and thereby inhibit fusion between the virus and the cell membrane.
cord-034363-6uscua0y	2020	
cord-253616-7jyui5ca	2020	
cord-254194-962vynwk	2011	
cord-256838-8rzibpbl	2019	There are still issues regarding the conflicting pharmacologic effects, pharmacokinetics, drug interactions, adverse and clinical effects of herbal medicine and TCM. Several factors may affect the molecular mechanisms and subsequent clinical effects of TCM formulas, including individual gene-based response, composition and amount of active molecules in TCM formulas, complex interactions, and appropriateness of use of TCM formulas. From the viewpoint of pathophysiology, TCM formulas used to manage airway viral infections need to have antiviral activity against such viruses listed above, and/or to induce antiviral cytokines, and/or anti-inflammatory effect, and/or to relieve symptoms commonly presented in airway infections ( Figure 1 ). To simplify the molecular mechanisms and to correlate the pharmacologic activities with their clinical effects, five formulas of A-physicians will be used as examples against airway infections: Several health benefits of herbal medicine and TCM are claimed; for example, herbs and TCM formulas, including those discussed above, are believed to have anti-oxidative activities helpful against several diseases.
cord-257581-trt6s1wp	2011	title: Three New Cycloartenol Triterpenoid Saponins from the Roots of Cimicifuga simplex Wormsk Three new cycloartenol triterpene saponins, named shengmaxinsides A-C, have been isolated from the ethyl acetate soluble fraction of an ethanol extract of Cimicifuga simplex Wormsk roots. simplex by column chromatography afforded three new cycloartane-type triterpenoid saponins ( Figure 1 ). The 13 C-NMR spectrum (Table 1) displayed a total of thirty eight carbon signals due to the aglycon moiety, along with a sugar unit and an acetyl unit. Its molecular formula was established as C 36 In the 13 C-NMR spectrum ( Table 1 ) a total of thirty six carbon signals due to the aglycon moiety were observed, along with a sugar unit. Four new glycosides from the aerial parts of Cimicifuga simplex Wormsk Eight new glycosides from Cimicifuga simplex Wormsk Twelve new cyclolanostanol glycosides from the underground parts of Cimicifuga simplex Wormsk
cord-259985-uysf83sh	2017	
cord-262094-b4yuh5y9	2018	
cord-264326-teahway7	2020	According to docking analysis the most promising results were found for HCV protease, DPP-4, α-thrombin and coagulation Factor Xa known inhibitors, with several of them exhibiting estimated free binding energy lower than −8.00 kcal/mol and better prediction results than reference compounds. Since the 3D structure of the active site of the enzyme is crucial for catalytic activity, we proceeded to a comparison of the SARS-CoV-2 main protease, Mpro, with the HIV-1 protease, the HCV protease (NS3 protein) and the human proteases DPP-4, thrombin, Factor Xa, renin and ACE, which constitute known drug targets with approved inhibitors. The structural similarity between the SARS-CoV-2 protease and some of the selected proteases, in combination with the existence of the same amino acids at certain positions of the substrate cleavage site, such as Ser at the P1'' position of the recognition sequence of the HCV protease and thrombin are promising features in the effort to identify effective SARS-CoV-2 protease inhibitors among the approved drugs of the selected proteases.
cord-266149-h8bu3jrq	2020	Signal Amplification by Reversible Exchange (SABRE), a hyperpolarization technique, has been harnessed as a powerful tool to achieve useful hyperpolarized materials by polarization transfer from parahydrogen. By performing SABRE in various magnetic fields and concentrations on nitrile compounds, we unveiled its hyperpolarization properties to maximize the spin polarization and its transfer to the next spins. Its optimal polarization factor with different magnetic fields and concentrations also showed the same trend as the butyronitrile case-an approximately 100-fold Its optimal polarization factor with different magnetic fields and concentrations also showed the same trend as the butyronitrile case-an approximately 100-fold enhancement in 70 G with a 5 µL amount of valeronitrile. By performing SABRE with various magnetic fields and substrate concentrations, we unveiled its hyperpolarization characteristics and properties to maximize the polarization and its transfer efficiency. By performing SABRE with various magnetic fields and substrate concentrations, we unveiled its hyperpolarization characteristics and properties to maximize the polarization and its transfer efficiency.
cord-268088-y4vg7frb	2020	Among the natural compounds that produce beneficial effects on human health, polyphenols have shown potential therapeutic applications in cancer due to their protective functions in plants, their use as food additives, and their excellent antioxidant properties. This review shows a wide range of trials in which polyphenolic compounds play a crucial role as anticancer medicines alone or in combination with other drugs at different stages of cancer: cancer initiation, promotion, and growth or progression. In point of fact, studies demonstrated that resveratrol has in vitro effects against a large range of human tumors: breast, skin, ovary, stomach, prostate, colon, liver, pancreas, cervix, thyroid carcinoma cells, lymphoid, and myeloid cancer cells [22] . In point of fact, studies demonstrated that resveratrol has in vitro effects against a large range of human tumors: breast, skin, ovary, stomach, prostate, colon, liver, pancreas, cervix, thyroid carcinoma cells, lymphoid, and myeloid cancer cells [22] .
cord-268902-npug5c8p	2015	
cord-272113-j82z4q8x	2020	
cord-272465-i2l4cq8h	2016	Hinders α-synuclein accumulation in neural cells and suppression of the proliferation of glioma cells through induction of autophagy [162, 163] Radix salviae miltiorrhizae (Dan shen) Moves blood, breaks up blood stasis, cools heat, cools blood Tanshinone IIA Induction of autophagic cell death of leukemia via activation of AMPK/mTOR, ERK/mTOR and p70 S6K signaling [164] Ligusticum wallichii (Chuan xiong) Moves blood, moves and regulates qi, dispels wind Ligustrazine Akebia saponin PA (AS) is one of the bioactive components found in Radix dipsaci, AS induced autophagic and apoptotic cell death of gastric cancer cells through both the AMPK/mTOR and PI3K/Akt/mTOR signaling and the downstream activation of p38/JNK molecular pathway, which facilitated capase-3-dependent apoptosis [147] . However, alisol B has been reported as a new autophagy inducer functioning through activation of CaMKK/AMPK/mTOR signaling, induction of apoptosis and triggering of cell death in breast cancer cells [156] . Gambogic acid induced oxidative stress dependent caspase activation regulates both apoptosis and autophagy by targeting various key molecules (Nf-κB, Beclin-1, p62 and NBR1) in human bladder cancer cells
cord-276598-tm0yj2sn	2020	For the low yielding derivatives, the reaction was more selective to three identified by-products, H-phosphonate, trialkyl phosphate, and tetraalkyl diphosphate, as well as some other unidentified Jang and coworkers reported a facile synthetic route to form P-Ns using diphenyl phosphoric acid (dPPA) and an amine in the presence of both a chlorinating agent (Cl 3 CCN) and a base (Et 3 N), which was added to sequester the acid formed during the reaction (Scheme 6c) [99] . proposed a reaction mechanism involving single-electron transfer oxidation of the copper catalyst, which favored the formation of the Cu(II)-amine complex (Scheme 27) [103] . proposed a reaction mechanism involving single-electron transfer oxidation of the copper catalyst, which favored the formation of the Cu(II)-amine complex (Scheme 27) [103] . [105] , the mechanism involves the formation of the (RO) 2 oxidized to form the Cu(III)-amine-phosphonate complex, which undergoes reductive elimination of the copper catalyst to yield the desired P-N.
cord-276781-ujvkcz4s	2020	At the same time, the benzimidazole L-riboside Maribavir is about to be evaluated in Phase III trials involving transplant recipients with HCMV infections that are refractory or resistant to the currently approved drugs as well as for its potential superiority over Valganciclovir in HSCT patients. However, initial Phase III clinical trials failed to prove sufficient benefits for post-transplant At the same time, the benzimidazole l-riboside Maribavir is about to be evaluated in Phase III trials involving transplant recipients with HCMV infections that are refractory or resistant to the currently approved drugs as well as for its potential superiority over Valganciclovir in HSCT patients. The resulting oil was purified by column chromatography, using a mixture of CHCl 3 /MeOH (99/1 to 97/3, v/v) as the eluent, to afford 8a, as a mixture with its corresponding α-anomer 9a (280 mg, total yield 53% for two anomers, 8a:9a (3-β:α) ratio 12:1, as estimated by 1 [4,5-b] pyridin-2-amine (11b): These derivatives were prepared by a procedure analogous to that described for 8a,9a,10a,11a, starting from imidazopyridine 7b (280 mg, 1.14 mmol).
cord-277491-q18b88lm	2011	
cord-279281-gh298gaa	2020	A natural hydrophilic DES constituted of sodium acetate (hydrogen bond acceptor) and formic acid (hydrogen bond donor) designed to evaluate the total phenolic compound (TPC), total flavonoid (TFC), total anthocyanin (TACN), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and ferric reducing antioxidant power (FRAP) values of Roselle. Nonetheless, C-H stretching weakened upon addition of water and disappeared completely in SAFAm. In the present study, sodium acetate:formic acid (1:2 molar ratio) was employed as a natural DES and coded as SAFA0 to extract polyphenolic compounds, especially anthocyanins and to evaluate the antioxidant activity of Roselle calyces. The reduced second-order models in terms of actual factors for the responses such as TPC, TFC, TACN, FRAP and DPPH radical scavenging values of Roselle calyces as a function of molarity ratio (X 1 ), additional water (X 2 ) and solvent to solid ratio (X 3 ) were obtained as follows: These equations showed up the response patterns for individual measurement and intricacy of sceneries.
cord-280292-90i45kjk	2020	The chemical interaction of AC with the NaOH solutions, having the concentration ranging between 0.001 and 0.3 M, induces a gradual enhancement of the photoluminescence excitation (PLE) and PL spectra, when the exposure time of samples at the UV light increases until 140 min, as a result of the formation of p-aminophenol and sodium acetate. According to Figure 2b -e, after 140 min of exposure to UV light, the AC interacted with the NaOH solutions having the concentrations equal to 10 −3 , 10 −2 , 10 −1 and 0.3 M, the intensity of the PL spectra is equal to 6.09 × 10 5 , 3.1 × 10 5 , 7.5 × 10 4 and 2.3 × 10 4 counts/sec, respectively. The interaction of the aqueous solution of Paracetamol with NaOH leads to a shift of the PLE band from 323 nm (Figure 3a ) to 337 nm (Figure 3c ), the subsequent exposure at UV light for 140 min inducing an intensity increase of the PLE band from 2.98 × 10 6 to 1.74 × 10 7 counts/sec.
cord-280807-0g1uo0rd	2020	noldeae, as well as caffeic acid, isoquercetin, and ER2.4 and ER2.7 fractions revealed significant inhibitory effects on Caspase-1 activities, and on IL-1β and IL-6 production. noldeae, as well as caffeic acid, isoquercetin, and ER2.4 and ER2.7 fractions revealed the highest inhibitory effects on Caspase-1 activities, and on IL-1β and IL-6 production. Therefore, we investigated the effect of our compounds and fractions of interest on inflammasome activation-induced cell death by measuring the release of lactate dehydrogenase (LDH) in the culture Concentrations of 20 µM YVAD and 20 µg/mL Dex were used as controls. Therefore, we investigated the effect of our compounds and fractions of interest on inflammasome activation-induced cell death by measuring the release of lactate dehydrogenase (LDH) in the culture supernatants. Before investigating the anti-inflammatory activity of different fractions, their effect on the cell viability (THP-1, monocytes and derived-macrophages, and RAW264.7) was screened as previously reported [21] .
cord-281281-knelqmzx	2020	The use of bioinformatics and other computational tools in addition to molecular modeling has helped researchers from different areas in the search for strategies for diagnosing viral infection, in the development of vaccines for its prevention, as well as in the discovery of new anti-SARS-CoV-2 agents. In the context of COVID-19, this characteristic was important for a better understanding of the origin of SARS-CoV-2 from the comparative analysis of genomic data of the new virus with others from the same family, suggesting its origin from natural selection, with modifications in its spike protein, more specifically in the host receptor binding domain, which may have enhanced its interaction and recognition by the human cell [83, 91] . The contributions of bioinformatics and molecular modeling in elucidating essential targets for the planning and development of new drugs, and the analysis of already known compounds, support the search for safer and more effective treatments against SARS-CoV-2 infection.
cord-281668-960trqex	2020	These inhibitors further provided the option of varying the leaving group that targets S2� site; more hydrophobic substituents were preferred at this position as comparison of ki/Ki values of the inactivation exhibited the following trend for Aa: Gly < Ala < Val < Leu < Phe < 4-NO2-Ph. The nitrophenyl analog (Entry 7, Table 2 ) which incur both hydrophobicity and electron-withdrawing property exerted the maximum potency and selectivity for cathepsin L over other tested cysteine proteases. These inhibitors further provided the option of varying the leaving group that targets S2� site; more hydrophobic substituents were preferred at this position as comparison of ki/Ki values of the inactivation exhibited the following trend for Aa: Gly < Ala < Val < Leu < Phe < 4-NO2-Ph. The nitrophenyl analog (Entry 7, Table 2 ) which incur both hydrophobicity and electron-withdrawing property exerted the maximum potency and selectivity for cathepsin L over other tested cysteine proteases.
cord-283127-jetmocvk	2015	
cord-284113-qboon2uv	2020	The hypothesis was that wild hemp would have a different EO content, composition, and antimicrobial activity compared with the EOs of registered industrial hemp cultivars, new hemp breeding lines, and a hemp strain (unregistered cultivar) that is currently used for the commercial production of CBD. Overall, the EOs of the wild hemps and registered cultivars in this study were similar to those reported previously: 0.23 to 0.31% in fresh inflorescences [14] , 0.29 to 0.19% depending on the collection time with higher EO yield from plants sampled earlier (in September than in October) [13] , and 0.1% in stems and 0.15% in the leaves of wild hemp from Austria [15] , respectively. Overall, the results from this study suggest that wild/spontaneous hemp in Europe is chemotaxonomically related to the industrial hemp varieties (cultivars) grown in Europe and deviate from the chemical profile of the USA hemp strain that was developed from marijuana-type cannabis for the commercial production of CBD.
cord-286655-5vorrnq3	2020	Lastly, we filtered the subset of phytochemicals whose binding energy in the best docked pose with TMPRSS2 (respectively, cathepsin L) is ≤−8.5 kcal/mol (respectively, ≤−8.0 In the third stage, we performed protein-ligand docking using AutoDock Vina [34] . Finally, in the fifth stage, for the top three inhibitors of TMPRSS2 namely, T1 (qingdainone), T2 (edgeworoside C) and T3 (adlumidine), and of cathepsin L namely, C1 (ararobinol), C2 ((+)-oxoturkiyenine) and C3 (3α,17α-cinchophylline), their respective protein-ligand complexes were analyzed using 180 ns MD simulation (Section 3; Figures 8 and 9; Supplementary Figures S1 and S2) and their interaction binding energy was computed using MM-PBSA method (Section 3; Table 3 ). As mentioned above, we have identified 96 potential natural product inhibitors of TMPRSS2 by computational screening of 14,011 phytochemicals produced by Indian medicinal plants, and these 96 compounds labelled T1-T96 are listed in Supplementary Table S1 along with their PubChem identifier, common name, IUPAC name and structure in SMILES format.
cord-287123-ldkuwcc7	2017	The formyl peptide receptors (FPRs) are G protein-coupled receptors that transduce chemotactic signals in phagocytes and mediate host-defense as well as inflammatory responses including cell adhesion, directed migration, granule release and superoxide production. N-formylated peptides constitute the most commonly studied class of FPR agonists that trigger a variety of biological activities in myeloid cells, such as chemokinesis, chemotaxis, calcium flux, cytokine production and superoxide anion generation. Through binding with the high affinity receptor FPR1, fMLF and other N-formylated peptides serve as potent chemoattractants, which also include activated complements (C5a, C3a) and chemokines, in recruiting and guiding leukocytes to the site of bacterial infection and to damaged tissues. As the first identified endogenous peptide agonist for FPR [56] , documented studies have shown that it exerts pro-inflammatory activities through FPR2 in phagocytes, epithelial cells and T lymphocytes, including stimulating production of inflammatory mediators and enhancing the expression of cytokine receptors [109] [110] [111] [112] [113] .
cord-287754-dh6abx2t	2015	Examples of lectins that exhibit antiviral activity and bind high-mannose carbohydrates are jacalin [25] , concanavalin A [26] , Urtica diocia agglutinin [27] , Myrianthus holstii lectin, P. The mannose-specific plant lectins Hippeastrum hybrid agglutinin, Galanthus nivalis agglutinin, Narcissus pseudonarcissus agglutinin; Cymbidium agglutinin; cyanovirin-N; and N-acetylglucosamine specific Urtica dioica agglutinin efficiently abrogate dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)-directed HIV-1 capture and subsequent transmission to T lymphocytes [55] . The nematode (Laxus oneistus) Ca 2+ -dependent C-type lectin Mermaid, a structural homologue of DC-SIGN devoid of cytotoxicity, shares the glycan specificity with DC-SIGN, interacts with high mannose structures on gp120 and prevents HIV-1 binding to DC-SIGN on DCs. Mermaid inhibits DC-SIGN-mediated HIV-1 transmission from DC to T cells. Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: Potential applications to microbicide development The high mannose-type glycan binding lectin actinohivin: Dimerization greatly improves anti-HIV activity
cord-289288-46nyje11	2019	Homonucleoside analogues cis-16 and trans-17 having a (5-methoxycarbonyl)isoxazolidine framework were synthesized via the 1,3-dipolar cycloaddition of nucleobase-derived nitrones with methyl acrylate. The synthetic strategy for γ-lactam homonucleosides 15 relies on the 1,3-dipolar cycloaddition of nucleobase-derived nitrones 13 with methyl acrylate, followed by the hydrogenolysis of the N-O bond in an isoxazolidine scaffold, which was accompanied by the intramolecular cyclization to transform cycloadducts 14 into compounds 15 (Scheme 1). The synthetic strategy for γ-lactam homonucleosides 15 relies on the 1,3-dipolar cycloaddition of nucleobase-derived nitrones 13 with methyl acrylate, followed by the hydrogenolysis of the N-O bond in an isoxazolidine scaffold, which was accompanied by the intramolecular cyclization to transform cycloadducts 14 into compounds 15 (Scheme 1). A series of isoxazolidine analogues of homonucleosides cis-14 and trans-14 was synthesized by 1,3-dipolar cycloaddition of nucleobase-derived nitrones 13 and methyl acrylate.
cord-290855-6umgvt28	2020	Previous studies have demonstrated essential oils to be excellent candidates to treat antiviral-resistant infection associated with their chemical complexity which confers broad-spectrum mechanisms of action and non-specific antiviral properties. This review provides an up-to-date overview of the antiviral efficacy of essential oils from a wide range of plant species and their characteristic components, as well as their overall mechanisms of action, focusing on the last decade. Virucidal effects of EOs extracted from numerous aromatic and herbal plants are also well documented on a variety of viruses, such as IFV, HSV, HIV, yellow fever virus, and avian influenza, etc. Essential oils from Star Anise, Australian tea tree, oregano, Eucalyptus caesia, to name a few, have been demonstrated to exhibit high anti-HSV-1 activities in vitro (Table 1 ).
cord-291180-xurmzmwj	2020	Then, virtual screening methods (e.g., molecular docking, pharmacophore modeling, and QSAR) as well as structureand ligand-based classical/de novo drug design were introduced and discussed. On the other hand, ligand-based drug design can also use quantitative structure-activity relationships (QSAR) [50, 51] in which a correlation between calculated properties of molecules and their experimentally determined biological activity is derived, to predict the activity of new analogs. With the assembly of reasonable molecular fragments, the objective of drug design method is to produce a certain novel molecule that display highest biological activity, absorption, metabolism, elimination (ADME) and lowest toxicity properties at different environments, which belong to the application range of QSAR models. With the booming era of "big" data, machine learning methods have developed into deep learning approaches, which are a more efficient way for drug designers to deal with important biological properties from large amount of compound databases.
cord-295171-vx4cypf7	2019	
cord-295229-dxl7wvcx	2013	The aim of this study was to elucidate the potential anti-inflammatory and anti-allergic activities of PHF, Moutan Cortex (Danpi/DP) and gallic acid (GA) using human basophils (KU812 cells), which are crucial effector cells in allergic inflammation. The aim of the present study was to elucidate the mechanisms of the in vitro anti-inflammatory and anti-allergic activities of PHF, Danpi and GA via their modulation of: (i) expression of cell surface adhesion molecules and (ii) the release of chemokines and cytokines from allergy-related alarmin IL-33-activated human basophils, which are crucial effector cells of allergic inflammation in allergic asthma and AD [27] . . Suppressive effect of inflammatory cytokine IL-6 release from IL-33-activated human basophilic KU812 cells treated with PHF (100, 500 and 1,000 μg/mL), DP (100, 500 and 1,000 μg/mL) or GA (10 and 100 μg/mL) for 18 h.
cord-299985-9954q0zg	2020	
cord-300872-blycbi4u	2020	Some of these strains have even become resistant to many antibiotics and chemotherapeutic agents; These prepared compounds were subjected to bioactivity screening against the highly pathogenic H5N1 avian influenza viruses, with the results expressed as percentages of growth inhibition, and to cytotoxicity evaluation against the A549 cell line. A synthetic procedure (Scheme 13) involved a condensation reaction between the amino group (NH2) in 49 and the carbonyl group in salicylic aldehyde (50), followed by intramolecular cyclization under a These prepared compounds were screened for potential anticancer activity against MCF-7, HCT 116, HepG-2, and A549 using the MMT assay. This compound was screened against MCF-7 and Hela cancer cell lines using MMT assay, giving IC50 values of 21.02 and 27.73 mM, respectively In addition, Shamsi and coworkers prepared 16 quinoline-based 1,3,4-oxadiazole-triazole derivatives (Scheme 14) based on the hybrid strategy of nitrogen-containing heterocyclic scaffolds [36] .
cord-302190-co4tju7u	2017	As a ubiquitous biflavonoid, amentoflavone has been found with a large number of pharmacological functions, such as anti-inflammation, anti-oxidation, anti-tumor, anti-senescence, anti-virus, anti-diabetes, neuroprotective activities, and effects on cardiovascular system and central nervous system. In another study, it was found that the naturally-occurring biflavonoid could prevent scopolamine-induced memory impairment, inhibit AChE and enhance antioxidant enzyme activity in mice, which exhibited its protection against memory deficits [176] . From the contents above, we could conclude that amentoflavone is a bioactive biflavonoid with a variety of pharmacological effects, which has been derived from many natural plants. Taken together, since amentoflavone is a promising and naturally-occurring biflavonoid with so many bioactivities, its systematic druggability research as a candidate drug is obviously necessary, including its preparation study (extraction and isolation from plants, chemical synthesis, or biological synthesis), structural modification study, Absorption-Distribution-Metabolism-Excretion (ADME) study in normal animals and animal models, acute and chronic toxicological studies.
cord-306633-69ljgkqy	2011	title: Benzylidene-bis-(4-Hydroxycoumarin) and Benzopyrano-Coumarin Derivatives: Synthesis, (1)H/(13)C-NMR Conformational and X-ray Crystal Structure Studies and In Vitro Antiviral Activity Evaluations We report on the synthesis of 4-hydroxycoumarin dimers 1–15 bearing an aryl substituent on the central linker and fused benzopyranocoumarin derivatives 16–20 and on their in vitro broad anti-DNA and RNA virus activity evaluations. The X-ray crystal structure analysis revealed that two 4-hydroxycoumarin moieties in the 4-trifluoromethylphenyland 2-nitrophenyl derivatives (compounds 7 and 9, respectively) are intramolecularly hydrogen-bonded between hydroxyl and carbonyl oxygen atoms. The 4-hydroxycoumarin moieties are intramolecularly hydrogen bonded between hydroxyl and carbonyl oxygen atoms in both structures (see Figures 4a and 4b and Table S1 in ESI), thus forming two eight-membered rings. X-ray crystal structure analysis of 4-trifluoromethylphenyl-and 2-nitrophenyl derivatives 7 and 9 revealed intramolecular hydrogen bonding between hydroxyl and carbonyl oxygen atoms of two 4-hydroxycoumarin moieties resulting in the formation of two eight-membered rings.
cord-307731-a2fqmaly	2020	In particular, the compounds obtained in the final rank order lead to meaningful increases in both performance and robustness over the single-modality approaches, but the results also demonstrate the sensitivity of the performance to the target structural details (i.e., the nature of the template ligand in measurements of molecular similarity and the reference protein pocket in docking studies) [67, 68] . In particular, the compounds obtained in the final rank order lead to meaningful increases in both performance and robustness over the single-modality approaches, but the results also demonstrate the sensitivity of the performance to the target structural details (i.e., the nature of the template ligand in measurements of molecular similarity and the reference protein pocket in docking studies) [67, 68] .
cord-309722-04pp3lv0	2016	Notes: AHR, airway hyperresponsiveness; ALI, Acute lung injury; BALF, bronchoalveolar lavage fluid; CD86, cluster of differentiation 86; C-kit, a stem cell factor receptor; DCs, dendritic cells; HMGB1A, high mobility group box-1 A peptide; IFU, infectious unit; LPS, lipopolysaccharide; Mpl, myeloproliferative leukemia virus oncogene; OVA, ovalbumin; R3V6, an arginine-rich peptide; Rip2, receptor-interacting protein 2; RSV, respiratory syncytial virus; S1Plyase, sphingosine-1-phosphate lyase, SOCS, Suppressors of cytokine signaling protein 3; STAT6, signal transducer and activator of transcription factor 6; Syk, spleen tyrosine kinase; Tf-PEI, transferrin polyethylenimine; T h 2, T helper 2 cells; TNF-α, tumor necrosis factor-α; VEGFR, Vascular endothelial growth factor. After siRNA targeting, SOCS3 was intranasally administered to the lungs of chronic asthmatic mouse model [12] , the silencing of SOCS3 down-regulated the expression of T h 2 cell associated cytokines, IL-4, IL-5 and IL-13, leading to substantial reduction of airway inflammation, AHR as well as IgE production.
cord-310268-8q4tk6fd	2015	Nucleic acid aptamers are RNA and single-stranded (ss) DNA oligonucleotides with lengths typically ranging from 15 to 70 mers, which have the same level of target-binding affinity as monoclonal antibodies (the dissociation constant (K d ) usually ranges from 0.1 to 50 nM) [5, 6] . This SELEX is able to generate DNA aptamers that recognize the cell-surface or intracellular target protein in their native conformation, which shows great potential in cell-specific therapeutics and diagnostic applications [26] [27] [28] . Recently, modified cell-SELEX methods have been developed to select aptamers targeting specific cells like disease state cells and metastatic cells. In the era of personalized medicine, DNA aptamer-based therapeutics and diagnostics are believed to have great potential for extensive application because of their flexibility to specifically bind to any molecule targets.
cord-313668-zz32fpvz	2015	title: Asteltoxins with Antiviral Activities from the Marine Sponge-Derived Fungus Aspergillus sp. Two new asteltoxins named asteltoxin E (2) and F (3), and a new chromone (4), together with four known compounds were isolated from a marine sponge–derived fungus, Aspergillus sp. Marine sponge-derived fungus tends to produce structurally unique and biologically active natural products which have been documented in recent years; however, only a handful of reports have described new metabolites which have antiviral activities [7, 8] . The fungal strain SCSIO XWS02F40 was isolated from the sponge Callyspongia sp., which was collected from the sea area near Xuwen County, Guangdong Province, China, during August 2013. The fungal strain SCSIO XWS02F40 was isolated from the sponge Callyspongia sp., which was collected from the sea area near Xuwen County, Guangdong Province, China, during August 2013. In conclusion, three new compounds, Asteltoxin E (2), Asteltoxin F (3) and 7-hydroxy-2-(2-hydroxypropyl)-5-pentyl chromone (4), together with four known compounds were isolated from a marine sponge-derived fungus, Aspergillus sp.
cord-316474-407bthqj	2011	Since the pioneering work described above, phage display technology has further been developed and improved by scientists from various fields, and its applications has extended from epitope mapping to antibody engineering and organ targeting [2] [3] [4] [5] . Mimotopes can now be obtained in a relatively cheap, efficient and convenient way, i.e. screening phage-displayed random peptide libraries with a given target. In this review, we will summarize the special databases, algorithms, programs, web servers and their applications in the phage display area, focusing on the tools for mimotope-based epitope mapping. With these tools, phage display technology has shown its power in exploring the interactions between proteins, peptides and small molecule ligands. Powered by special computational tools developed for phage display technology, not only linear epitope but also conformational epitope formed by discontinuous residues brought into spatial proximity by protein folding can be mapped reasonably.
cord-320143-08gk0nmi	2020	
cord-324829-0nz0qioh	2017	Gold nanoparticles, in general, have remarkably high surface-to-volume ratio, are biocompatible and inert, and can be easily functionalized with several molecules; thus, they can also play an important role in the vaccine field as adjuvants, reducing toxicity, enhancing immunogenic activity, and providing stability of vaccine in storage, and have great potential as carriers for the development of a great diversity of fully synthetic vaccines [8] [9] [10] [11] [12] 15, 20, 21, 26, [48] [49] [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61] . Gold nanoparticles, in general, have remarkably high surface-to-volume ratio, are biocompatible and inert, and can be easily functionalized with several molecules; thus, they can also play an important role in the vaccine field as adjuvants, reducing toxicity, enhancing immunogenic activity, and providing stability of vaccine in storage, and have great potential as carriers for the development of a great diversity of fully synthetic vaccines [8] [9] [10] [11] [12] 15, 20, 21, 26, [48] [49] [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61] .
cord-330253-9sqizkio	2020	Six different batches of blank human plasma, OTN raw material (99.0%), Alogliptin raw material, internal standard (IS) (99.2%), Marizev ® (12.5 mg) tablets, tertiary butyl methyl ether (TBME), diethyl ether (DEE) were kindly donated by the British University in Egypt (CDRD, BUE) based on previous research collaborations (Repositioning CDRD-BUE project). Therefore, an advanced analytical technique and enhanced extraction of drugs from human plasma become a challenging approach that greatly affects pharmacokinetics, other clinical studies based on the drug C min and C max values and the bio-analytical methods sensitivity. The authors mentioned in the current study modified the rats'' plasma method [18] in another repositioning publication [11] but with direct precipitation with acetonitrile, the LLOQ was 50 ng/mL which is very high in comparison to the LLOQ in the current work with the enhanced extraction technique (9.98 ng/mL equivalent to 25 nM).
cord-330813-43l9m0yh	2020	These results suggest that the insoluble powder was CaCO3 generated by an interaction between Ca 2+ ions in BiSCaO Water and CO2 in the air, and that the BiSCaO suspension, dispersion, and colloidal dispersion contained insoluble CaO and/or Ca(OH)2 in the form of micro-/nano-particles or precipitates that provide hydroxyl ions (OH -) to maintain the alkaline pH. Although the CFU/mL for TC and CF following treatment with undiluted (final two-fold diluted) BiSCaO Water and 0.4 (final 0.2 wt.%) BiSCaO suspension, dispersion, and colloidal dispersion exhibited high disinfection activities (>5 log decreases in CFU/mL), a small part of TC (>1000 CFU/mL) and CF (>100 CFU/mL) remained viable (Figure 7) . Although the CFU/mL for TC and CF following treatment with undiluted (final two-fold diluted) BiSCaO Water and 0.4 (final 0.2 wt.%) BiSCaO suspension, dispersion, and colloidal dispersion exhibited high disinfection activities (>5 log decreases in CFU/mL), a small part of TC (>1000 CFU/mL) and CF (>100 CFU/mL) remained viable (Figure 7) .
cord-331504-b68y9hxw	2016	Our synthetic strategy to compounds trans-11/cis-11 relies on the 1,3-dipolar cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone 12 [36] with 2-vinyl-3H-quinazolin-4-ones 13 substituted at N3 (Scheme 1). Our synthetic strategy to compounds trans-11/cis-11 relies on the 1,3-dipolar cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone 12 [36] with 2-vinyl-3H-quinazolin-4-ones 13 substituted at N3 (Scheme 1). Our synthetic strategy to compounds trans-11/cis-11 relies on the 1,3-dipolar cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone 12 [36] with 2-vinyl-3H-quinazolin-4-ones 13 substituted at N3 (Scheme 1). However, attempts to isolate pure diastereoisomers were fruitful for trans-11a The relative configurations of isoxazolidines trans-11a and cis-11a were established based on our previous studies on stereochemistry of cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone (12) with various vinyl aryls [39, 40] since similar 1 H-NMR spectral patters for the respective series of trans-and cis-isoxazolidines were observed. After incubation at 37˝C for two (L1210), three (CEM) or four (HeLa) days, the cell number was determined of isoxazolidine-containing quinazolinones trans-11 and cis-11 have been synthesised from N-methyl-C-diethoxyphosphorylnitrone (12) and the respective N3-substituted 2-vinyl-quinazolin-ones 13 via the 1,3-dipolar cycloaddition.
cord-334511-lx9608vy	2020	The nearly ubiquitous use of virtual screening is due to its efficiency in searching massive chemical databases in order to generate lead molecules [313] that inhibit protein-protein interactions [314] , and its ability to help identity ligand (drug) binding sites on the target of interest [310] to lend insight to the mechanisms of action for lead compounds [315, 316] . The nearly ubiquitous use of virtual screening is due to its efficiency in searching massive chemical databases in order to generate lead molecules [313] that inhibit protein-protein interactions [314] , and its ability to help identity ligand (drug) binding sites on the target of interest [310] to lend insight to the mechanisms of action for lead compounds [315, 316] . Clearly, combining virtual screening with NMR-based methods is advantageous in studying how ligands (drugs) bind and interact with targets (proteins) of interest. The interactions between targets (proteins) and ligands (small molecules) can be analyzed independently of the biological systems by using ''cell-based'' NMR drug design approaches.
cord-340879-gu91cact	2017	title: Isolation and Characterization of a Phaseolus vulgaris Trypsin Inhibitor with Antiproliferative Activity on Leukemia and Lymphoma Cells The intent of the present study was to isolate a trypsin inhibitor from the gold bean and to test it for inhibitory action on tumor cells, viral enzymes, and fungal growth. Gold bean trypsin inhibitor is also devoid of any inhibitory effect on HIV-1 integrase and SARS coronavirus proteinase. Gold bean trypsin inhibitor is also devoid of any inhibitory effect on HIV-1 integrase and SARS coronavirus proteinase. A lectin, an antifungal protein and a trypsin inhibitor can be isolated from the gold bean [24, 25] . A homodimeric sporamin-type trypsin inhibitor with antiproliferative, hiv reverse transcriptase-inhibitory and antifungal activities from wampee (clausena lansium) seeds The isolation of two proteins, glycoprotein i and a trypsin inhibitor, from the seeds of kidney bean (Phaseolus vulgaris)
cord-344175-e2m9o8c2	2020	
cord-347992-coby2m6e	2010	Although ribozymes and DNAzymes have been extensively assayed as potential therapeutic agents, and different clinical trials have already tested their efficiency against various diseases [49] [50] [51] [52] , very few reports have described the direct application of in vitro selection strategies in the development of potentially therapeutic catalytic nucleic acids. Molecular studies have shown that this aptamer binds to the cell surface protein nucleolin and inhibits the activity of NF-KB, a ubiquitous transcription factor, through intracellular complex formation [108] . In a different approach, SELEX has been performed with the E2F1 protein to find in vitro selected RNA aptamers that bind to and inhibit E2F activity. Astier-Gi''s group described the characterization of two DNA aptamers (27v and 127v) that specifically bind to hepatitis C virus (HCV) RNA polymerase (NS5B), inhibiting its activity in vitro [146] . In vitro selection procedures for identifying DNA and RNA aptamers targeted to nucleic acids and proteins
cord-349672-2kt7xw8i	2020	Here, based on available structural and biochemical data, we discuss how a type IA topoisomerase may recognize and bind single-stranded DNA or RNA to initiate its required catalytic function. In type IA topoisomerases, the hydroxyl group in the side chain of the active site tyrosine residue is responsible for the first nucleophilic attack on the scissile phosphate of a single-stranded DNA resulting in the cleavage of the G-strand and the formation of the transient 5 -phospho-tyrosyl covalent linkage [66] . Though the type IA topoisomerase core domain that forms the characteristic torus structure contains all the highly conserved motifs responsible for G-strand binding and cleavage religation, the C-terminal domains of bacterial topoisomerase I have been shown to be required for removing negative supercoils from DNA rapidly in a processive mechanism [61, 72, [84] [85] [86] [87] .
cord-352513-15nalst7	2020	Electrophoretic separation technique has been used in µPADs as a sample preparation step in various analytical detection methods such as ion-transmission mass spectrometry (MS) for analysis of amino acids [97] , matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for detection of albumin and glycated hemoglobin (HBA1c) [98] , and lateral flow immunoassay (LFA) for the detection of IgG [90] Typically, fluid control and programmability are vital to automate and to minimize the processing in the fabrication and the operation, but maximize the use of µPADs. By controlling the fluid flow in the µPAD, researchers have been able to achieve high-sensitivity detection and automated programmable assays [99, 100] . Even though µPADs provide extraordinary advantages, including simple fabrication and mass-scalability at an affordable cost, if an advanced paper-based analytical device providing high performance and sensitivity is to be achieved, suitable detection mechanisms are necessary for the µPADs. The most common detection techniques in µPADs are colorimetric, electrochemical, chemiluminescent, and electrochemiluminescent techniques.
cord-352891-ljmkqdzx	2020	title: Comparative Antiviral Activity of Remdesivir and Anti-HIV Nucleoside Analogs against Human Coronavirus 229E (HCoV-229E) Herein, we report the antiviral activity of remdesivir against human coronavirus 229E (HCoV-229E) compared to known anti-HIV agents. These agents included tenofovir (TFV), 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA), alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC), known as nucleoside reverse-transcriptase inhibitors (NRTIs), and a number of 5′-O-fatty acylated anti-HIV nucleoside conjugates. Therefore, HCoV-229E may be a good initial model for the evaluation of antiviral compounds that could have potential applications against other coronaviruses, such as SARS-COV-2, the coronavirus that causes COVID-19. We have previously shown that the conjugation of certain fatty acids to the anti-HIV NRTIs, such as FLT, 3TC and FTC, enhanced activity against X4, R5, cell-associated, and/or multi-drug resistant virus when compared with their parent nucleosides [24] [25] [26] [27] . A series of anti-HIV nucleosides and their fatty acyl derivatives were compared with remdesivir for antiviral activity against HCoV-229E in MRC-5 cells.
cord-353494-72fvkx7f	2020	The RMSD plots of all the three ligand-protein complexes showed very stable conformation throughout the simulation study, which demonstrates that it has a huge impact on the Mpro target ( Figure S2A ) as the reference compound N3. RMSF study of the three natural compounds with SARS-COV-2 Mpro showed very less fluctuations, and the value was found to be less than 0.2 nm, which indicates that the ligands bind properly with the active sites of the protein such as the reference compounds ( Figure S3A ). RMSF study of the three natural compounds with SARS-COV-2 Mpro showed very less fluctuations, and the value was found to be less than 0.2 nm, which indicates that the ligands bind properly with the active sites of the protein such as the reference compounds ( Figure S3A ). The molecular dynamic simulation showed that the selected natural compounds bind and stabilized the active site of both the proteins such as Mpro and TMPRSS2.
cord-355685-wgad0eoh	2020	Compounds 6, 8, 16 and 17, bearing the 5-(thio)semicarbazone and 5-hydrazone functionalities in combination with the 2-benzyl ring on the benzimidazole core structure, acted as dual inhibitors of influenza A virus and human coronavirus. For respiratory syncytial virus (RSV), activity is limited to the 5-thiosemicarbazone (25) and 5-hydrazone (22) compounds carrying the 2-[(benzotriazol-1/2-yl)methyl]benzimidazole scaffold. The herein-investigated benzimidazole-based derivatives may represent valuable hit compounds, deserving subsequent structural improvements towards more efficient antiviral agents for the treatment of pathologies caused by these human respiratory viruses. For RSV, activity is restricted to the 5-(thio)semicarbazone (25) and hydrazone (22) compounds carrying the 2-[(benzotriazol-1/2-yl)methyl]benzimidazole scaffold, in line with the previously synthesized analogues (see above), which show comparable potency in the low micromolar range. In summary, this study reports the synthesis of a series of (thio)semicarbazone-and hydrazone-containing benzimidazoles for the development of novel antiviral agents which have shown the ability to inhibit the replication of three human respiratory viruses.