{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:03:10Z","timestamp":1787022190643,"version":"build-2736575974"},"reference-count":92,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    <jats:italic>Mammalian orthoreoviruses<\/jats:italic>\n                    (MRVs), commonly known as reoviruses, are an emerging zoonotic threat that are known for their broad host tropism and potential for causing severe clinical pathology in both humans and animals. Despite this epidemic risk, currently, there are no approved therapeutic agents that are able to disrupt MRV transmission. The viral attachment protein sigma1 (\u03c31), mediating the entry of the virus into the host cells is a critical target for antiviral intervention. This study used an\n                    <jats:italic>in silico<\/jats:italic>\n                    structure-based drug design strategy to screen for bioactive phytochemicals that are capable of inhibiting the function of \u03c31. We screened a library of 376 bioactive phytochemicals with known antiviral potential against the \u03c31 receptor binding domain using molecular docking. Among the candidates, catechin gallate was the most potent inhibitor, possessing a superior binding affinity of \u22128.1 kcal\/mol followed by bilobetin, which also showed a favorable binding affinity of \u22127.8 kcal\/mol. Structural interaction analysis showed that catechin gallate and bilobetin occupies the active JAM-A binding pocket, forming stable interactions with some of the residues, including Gly381, Glu384, and Arg316, which are essential for the reovirus in the cellular attachment process. Subsequent pharmacokinetic and toxicity profiling proved that catechin gallate possessed favorable safety and drug-like characteristics, whereas bilobetin exhibited an unfavorable toxicity profile. In addition, molecular dynamics (MD) simulations supported the stability of \u03c31-catechin gallate complex relative to the \u03c31-bilobetin complex. Extensive post-trajectory analyses including RMSD, RMSF, Rg, SASA, and H-bond, showed that the binding of the catechin gallate significantly increases the rigidity and compactness of the protein. PCA indicated that the first three principal components (PC1-PC3) accounted for 74.1% and 76.2% of the total variance for catechin gallate and bilobetin, respectively, with the \u03c31-catechin gallate complex displaying a more compact conformational cluster consistent with greater stability. MM-GBSA analysis also showed favorable binding for both complexes, with estimated binding energies of \u221215.6097\u2009\u00b1\u20093.21 kcal\/mol and \u221213.7327\u2009\u00b1\u20095.44 kcal\/mol for the \u03c31-catechin gallate and \u03c31-bilobetin complexes, respectively, with catechin gallate showing comparatively stronger binding. Our results reveal a precise mechanism by which the lead compound catechin gallate sterically occludes the \u03c31 receptor-binding pocket, thereby likely abrogating viral attachment to the host cell. This comprehensive preclinical evaluation provides supporting evidence for the further development of catechin gallate using\n                    <jats:italic>in vivo<\/jats:italic>\n                    models and clinical trials as a promising antiviral candidate against reovirus infection.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0350009","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T17:41:11Z","timestamp":1780508471000},"page":"e0350009","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["In silico characterization of bioactive phytochemicals as antivirals targeting the reovirus \u03c31 protein for inhibiting \u03c31-mediated host cell entry"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8126-6616","authenticated-orcid":true,"given":"Eitu","family":"Dey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0795-9340","authenticated-orcid":true,"given":"Shipon","family":"Dey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leu","family":"Nandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1048-4072","authenticated-orcid":true,"given":"Sayed Huzaifa","family":"Mumit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Refatul","family":"Arfat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saifur Rahman","family":"Saif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3922-9190","authenticated-orcid":true,"given":"Md. Monirul","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"pone.0350009.ref001","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.virol.2022.02.001","article-title":"The interactions of flaviviruses with cellular receptors: Implications for virus entry","volume":"568","author":"MN Anwar","year":"2022","journal-title":"Virology"},{"issue":"17","key":"pone.0350009.ref002","doi-asserted-by":"crossref","first-page":"2590","DOI":"10.1016\/j.jmb.2018.06.024","article-title":"Virus-Receptor Interactions: The Key to Cellular Invasion","volume":"430","author":"MS Maginnis","year":"2018","journal-title":"J Mol Biol"},{"key":"pone.0350009.ref003","doi-asserted-by":"crossref","first-page":"469538","DOI":"10.1155\/2013\/469538","article-title":"Virus entry by endocytosis","volume":"2013","author":"AV Nicola","year":"2013","journal-title":"Adv Virol"},{"key":"pone.0350009.ref004","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1146\/annurev.micro.56.012302.160643","article-title":"Common principles in viral entry","volume":"56","author":"MM Poranen","year":"2002","journal-title":"Annu Rev Microbiol"},{"issue":"1661","key":"pone.0350009.ref005","doi-asserted-by":"crossref","first-page":"20140035","DOI":"10.1098\/rstb.2014.0035","article-title":"The role of cellular adhesion molecules in virus attachment and entry","volume":"370","author":"D Bhella","year":"2015","journal-title":"Philos Trans R Soc B Biol Sci"},{"issue":"3","key":"pone.0350009.ref006","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/S0092-8674(01)00231-8","article-title":"Junction adhesion molecule is a receptor for reovirus","volume":"104","author":"ES Barton","year":"2001","journal-title":"Cell"},{"key":"pone.0350009.ref007","article-title":"Family Reoviridae","volume-title":"Virus Taxonomy: Ninth Report of the International 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Duncan","year":"2019","journal-title":"Annu Rev Virol"},{"issue":"2","key":"pone.0350009.ref011","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ymeth.2011.07.002","article-title":"Reverse genetics for mammalian reovirus","volume":"55","author":"KW Boehme","year":"2011","journal-title":"Methods"},{"issue":"1","key":"pone.0350009.ref012","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1038\/s41598-020-58003-9","article-title":"Novel human reovirus isolated from children and its long-term circulation with reassortments","volume":"10","author":"SP Yamamoto","year":"2020","journal-title":"Sci Rep"},{"key":"pone.0350009.ref013","doi-asserted-by":"crossref","first-page":"105421","DOI":"10.1016\/j.meegid.2023.105421","article-title":"Mammalian orthoreoviruses exhibit rare genotype variability in genome constellations","volume":"110","author":"JR Diller","year":"2023","journal-title":"Infect Genet 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Bokiej","year":"2012","journal-title":"J Virol"},{"issue":"23","key":"pone.0350009.ref018","doi-asserted-by":"crossref","first-page":"10951","DOI":"10.1128\/JVI.01843-16","article-title":"Reovirus \u03bc1 Protein Affects Infectivity by Altering Virus-Receptor Interactions","volume":"90","author":"D Thete","year":"2016","journal-title":"J Virol"},{"key":"pone.0350009.ref019","volume-title":"The role of sialic acid binding in reovirus neuropathogenesis","author":"JM Frierson","year":"2012"},{"issue":"13","key":"pone.0350009.ref020","doi-asserted-by":"crossref","first-page":"7967","DOI":"10.1128\/JVI.79.13.7967-7978.2005","article-title":"Junctional adhesion molecule a serves as a receptor for prototype and field-isolate strains of mammalian reovirus","volume":"79","author":"JA Campbell","year":"2005","journal-title":"J Virol"},{"key":"pone.0350009.ref021","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/82_2010_32","article-title":"From touchdown to transcription: the reovirus cell entry pathway","volume-title":"Cell entry by non-enveloped viruses","author":"P Danthi","year":"2010"},{"issue":"8","key":"pone.0350009.ref022","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1161\/CIRCRESAHA.120.316742","article-title":"JAM-A Acts via C\/EBP-\u03b1 to Promote Claudin-5 Expression and Enhance Endothelial Barrier Function","volume":"127","author":"N Kakogiannos","year":"2020","journal-title":"Circ Res"},{"issue":"30","key":"pone.0350009.ref023","doi-asserted-by":"crossref","first-page":"10634","DOI":"10.1073\/pnas.0500147102","article-title":"Junctional adhesion molecule-A-deficient polymorphonuclear cells show reduced diapedesis in peritonitis and heart ischemia-reperfusion injury","volume":"102","author":"M Corada","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0350009.ref024","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1081\/RRS-120034252","article-title":"Signaling pathways of the F11 receptor (F11R; a.k.a. 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Orthoreoviruses. 2013."},{"issue":"10","key":"pone.0350009.ref034","doi-asserted-by":"crossref","first-page":"6709","DOI":"10.1128\/jvi.70.10.6709-6715.1996","article-title":"Reovirus-induced acute myocarditis in mice correlates with viral RNA synthesis rather than generation of infectious virus in cardiac myocytes","volume":"70","author":"B Sherry","year":"1996","journal-title":"J Virol"},{"key":"pone.0350009.ref035","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/1743-422X-10-67","article-title":"Respiratory infection of mice with mammalian reoviruses causes systemic infection with age and strain dependent pneumonia and encephalitis","volume":"10","author":"L Gauvin","year":"2013","journal-title":"Virol J"},{"issue":"6","key":"pone.0350009.ref036","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.chom.2014.05.010","article-title":"The Nogo receptor NgR1 mediates infection by mammalian reovirus","volume":"15","author":"JL Konopka-Anstadt","year":"2014","journal-title":"Cell Host Microbe"},{"issue":"20","key":"pone.0350009.ref037","doi-asserted-by":"crossref","first-page":"11040","DOI":"10.1128\/JVI.78.20.11040-11050.2004","article-title":"Caspase inhibition protects against reovirus-induced myocardial injury in vitro and in vivo","volume":"78","author":"RL DeBiasi","year":"2004","journal-title":"J Virol"},{"key":"pone.0350009.ref038","doi-asserted-by":"crossref","first-page":"197642","DOI":"10.1016\/j.virusres.2019.197642","article-title":"Molecular characterization of a novel reassortment Mammalian orthoreovirus type 2 isolated from a Florida white-tailed deer fawn","volume":"270","author":"MS Ahasan","year":"2019","journal-title":"Virus Res"},{"issue":"1","key":"pone.0350009.ref039","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1186\/s12917-018-1585-y","article-title":"Identification of novel reassortant mammalian orthoreoviruses from bats in Slovenia","volume":"14","author":"T Nagli\u010d","year":"2018","journal-title":"BMC Vet Res"},{"issue":"8","key":"pone.0350009.ref040","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0043106","article-title":"Isolation and characterization of three mammalian orthoreoviruses from European bats","volume":"7","author":"C Kohl","year":"2012","journal-title":"PLoS One"},{"issue":"8","key":"pone.0350009.ref041","first-page":"1436","article-title":"Novel human reovirus isolated from children with acute necrotizing encephalopathy","volume":"17","author":"LA Ouattara","year":"2011","journal-title":"Emerg Infect Dis"},{"key":"pone.0350009.ref042","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/s12985-016-0593-4","article-title":"First identification of mammalian orthoreovirus type 3 in diarrheic pigs in Europe","volume":"13","author":"D Lelli","year":"2016","journal-title":"Virol 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Milwaukee, Wisconsin (August 1994 through July 2003)","volume":"71","author":"G Sedmak","year":"2005","journal-title":"Appl Environ Microbiol"},{"issue":"10","key":"pone.0350009.ref046","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1111\/j.1348-0421.2006.tb03854.x","article-title":"Detection of enteroviruses and mammalian reoviruses in Korean environmental waters","volume":"50","author":"HJ Kim","year":"2006","journal-title":"Microbiol Immunol"},{"key":"pone.0350009.ref047","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.vetmic.2017.07.021","article-title":"Genetic and pathogenic characterization of a novel reassortant mammalian orthoreovirus 3 (MRV3) from a diarrheic piglet and seroepidemiological survey of MRV3 in diarrheic pigs from east China","volume":"208","author":"P Qin","year":"2017","journal-title":"Vet Microbiol"},{"key":"pone.0350009.ref048","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.vetmic.2011.12.032","article-title":"Detection and molecular characterization of porcine type 3 orthoreoviruses circulating in South Korea","volume":"157","author":"H-J Kwon","year":"2012","journal-title":"Vet Microbiol"},{"issue":"3","key":"pone.0350009.ref049","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1292\/jvms.55.453","article-title":"Isolation of reovirus type 3 from dogs with diarrhea","volume":"55","author":"T Kokubu","year":"1993","journal-title":"J Vet Med Sci"},{"key":"pone.0350009.ref050","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.vetmic.2005.05.014","article-title":"Virological and molecular characterization of a mammalian orthoreovirus type 3 strain isolated from a dog in Italy","volume":"109","author":"N Decaro","year":"2005","journal-title":"Vet Microbiol"},{"issue":"08","key":"pone.0350009.ref051","doi-asserted-by":"crossref","first-page":"212","DOI":"10.55640\/ijmsdh-11-08-27","article-title":"Viral Immune Evasion Strategies and Their Impact on Antiviral Therapy and Vaccine Development: A Review","volume":"11","author":"NH Sarhan","year":"2025","journal-title":"ijmsdh"},{"key":"pone.0350009.ref052","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1471-2164-8-6","article-title":"An annotated catalogue of salivary gland transcripts in the adult female mosquito, Aedes aegypti","volume":"8","author":"JMC Ribeiro","year":"2007","journal-title":"BMC Genomics"},{"issue":"2","key":"pone.0350009.ref053","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1128\/MMBR.00049-13","article-title":"Virus world as an evolutionary network of viruses and capsidless selfish elements","volume":"78","author":"EV Koonin","year":"2014","journal-title":"Microbiol Mol Biol Rev"},{"issue":"5","key":"pone.0350009.ref054","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S0041-0101(00)00154-9","article-title":"Plants as source of drugs","volume":"39","author":"SM Rates","year":"2001","journal-title":"Toxicon"},{"issue":"4","key":"pone.0350009.ref055","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1637\/aviandiseases-D-22-99994","article-title":"Evaluation of Pathogenicity and Antigenicity of Avian Reoviruses and Disease Control Through Vaccination","volume":"66","author":"M Markis","year":"2022","journal-title":"Avian Dis"},{"issue":"8","key":"pone.0350009.ref056","doi-asserted-by":"crossref","first-page":"817","DOI":"10.3390\/vaccines9080817","article-title":"Evaluation of Avian Reovirus S1133 Vaccine Strain in Neonatal Broiler Chickens in Gastrointestinal Integrity and Performance in a Large-Scale Commercial Field Trial","volume":"9","author":"VM Petrone-Garcia","year":"2021","journal-title":"Vaccines (Basel)"},{"issue":"12","key":"pone.0350009.ref057","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1080\/07391102.2018.1506362","article-title":"Molecular dynamics and combined docking studies for the identification of Zaire ebola virus inhibitors","volume":"37","author":"KO Sulaiman","year":"2019","journal-title":"J Biomol Struct Dyn"},{"key":"pone.0350009.ref058","doi-asserted-by":"crossref","first-page":"104851","DOI":"10.1016\/j.compbiomed.2021.104851","article-title":"In silico methods and tools for drug discovery","volume":"137","author":"B Shaker","year":"2021","journal-title":"Comput Biol Med"},{"key":"pone.0350009.ref059","article-title":"The RCSB protein data bank: integrative view of protein, gene and 3D structural information","volume":"45","author":"PW Rose","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"pone.0350009.ref060","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/emboj\/21.1.1","article-title":"Crystal structure of reovirus attachment protein sigma1 reveals evolutionary relationship to adenovirus fiber","volume":"21","author":"JD Chappell","year":"2002","journal-title":"EMBO J"},{"issue":"2","key":"pone.0350009.ref061","doi-asserted-by":"crossref","DOI":"10.1002\/wcms.1298","article-title":"Using PyMOL as a platform for computational drug design","volume":"7","author":"S Yuan","year":"2017","journal-title":"WIREs Comput Mol Sci"},{"issue":"1","key":"pone.0350009.ref062","doi-asserted-by":"crossref","first-page":"22","DOI":"10.24198\/ijcb.v2i1.46322","article-title":"Molecular interaction analysis and visualization of protein-ligand docking using Biovia Discovery Studio Visualizer","volume":"2","author":"SS Baroroh","year":"2023","journal-title":"IJCB"},{"issue":"2","key":"pone.0350009.ref063","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/bib\/2.2.195","article-title":"Swiss-PDB Viewer (Deep View)","volume":"2","author":"W Kaplan","year":"2001","journal-title":"Brief Bioinform"},{"key":"pone.0350009.ref064","article-title":"PubChem Substance and Compound databases","volume":"44","author":"S Kim","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"pone.0350009.ref065","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1002\/(SICI)1096-987X(199604)17:5\/6<490::AID-JCC1>3.0.CO;2-P","article-title":"Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94","volume":"17","author":"TA Halgren","year":"1996","journal-title":"J Comput Chem"},{"issue":"1","key":"pone.0350009.ref066","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"A Daina","year":"2017","journal-title":"Sci Rep"},{"issue":"4","key":"pone.0350009.ref067","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ddtec.2004.11.007","article-title":"Lead- and drug-like compounds: the rule-of-five revolution","volume":"1","author":"CA Lipinski","year":"2004","journal-title":"Drug Discov Today Technol"},{"key":"pone.0350009.ref068","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkae303","article-title":"ProTox 3.0: a webserver for the prediction of toxicity of chemicals","volume":"52","author":"P Banerjee","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"pone.0350009.ref069","doi-asserted-by":"crossref","first-page":"790","DOI":"10.53555\/AJBR.v27i3S.2119","article-title":"A review on step into the future: Python prescription (PyRx) transforms virtual drug discovery with AI-driven tools","author":"DC Kannan","year":"2024","journal-title":"Afr J Biomed Res"},{"issue":"12","key":"pone.0350009.ref070","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1000235","article-title":"Structure of reovirus sigma1 in complex with its receptor junctional adhesion molecule-A","volume":"4","author":"E Kirchner","year":"2008","journal-title":"PLoS Pathog"},{"key":"pone.0350009.ref071","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","author":"MJ Abraham","year":"2015","journal-title":"SoftwareX"},{"issue":"4","key":"pone.0350009.ref072","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1002\/jcc.21367","article-title":"CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields","volume":"31","author":"K Vanommeslaeghe","year":"2010","journal-title":"J Comput Chem"},{"issue":"25","key":"pone.0350009.ref073","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1002\/jcc.23354","article-title":"CHARMM36 all-atom additive protein force field: validation based on comparison to NMR data","volume":"34","author":"J Huang","year":"2013","journal-title":"J Comput Chem"},{"issue":"10","key":"pone.0350009.ref074","doi-asserted-by":"crossref","first-page":"6281","DOI":"10.1021\/acs.jctc.1c00645","article-title":"gmx_MMPBSA: A New Tool to Perform End-State Free Energy Calculations with GROMACS","volume":"17","author":"MS Vald\u00e9s-Tresanco","year":"2021","journal-title":"J Chem Theory Comput"},{"key":"pone.0350009.ref075","doi-asserted-by":"crossref","first-page":"1254230","DOI":"10.3389\/fmolb.2023.1254230","article-title":"Combining docking, molecular dynamics simulations, AD-MET pharmacokinetics properties, and MMGBSA calculations to create specialized protocols for running effective virtual screening campaigns on the autoimmune disorder and SARS-CoV-2 main protease","volume":"10","author":"EI Edache","year":"2023","journal-title":"Front Mol Biosci"},{"issue":"11","key":"pone.0350009.ref076","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.3390\/cells11111757","article-title":"Reovirus activated cell death pathways","volume":"11","author":"C DeAntoneo","year":"2022","journal-title":"Cells"},{"issue":"2","key":"pone.0350009.ref077","doi-asserted-by":"crossref","first-page":"238","DOI":"10.3390\/v13020238","article-title":"Mammalian Orthoreovirus (MRV) Is Widespread in Wild Ungulates of Northern Italy","volume":"13","author":"S Arnaboldi","year":"2021","journal-title":"Viruses"},{"issue":"6333","key":"pone.0350009.ref078","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1126\/science.aah5298","article-title":"Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease","volume":"356","author":"R Bouziat","year":"2017","journal-title":"Science"},{"issue":"23","key":"pone.0350009.ref079","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.00974-18","article-title":"Reovirus Neurotropism and Virulence Are Dictated by Sequences in the Head Domain of the Viral Attachment Protein","volume":"92","author":"DM Sutherland","year":"2018","journal-title":"J Virol"},{"issue":"7","key":"pone.0350009.ref080","doi-asserted-by":"crossref","first-page":"13384","DOI":"10.3390\/molecules200713384","article-title":"Molecular docking and structure-based drug design strategies","volume":"20","author":"LG Ferreira","year":"2015","journal-title":"Molecules"},{"key":"pone.0350009.ref081","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/978-1-4939-9752-7_2","article-title":"Integrating molecular docking and molecular dynamics simulations","volume-title":"Docking screens for drug discovery","author":"LH Santos","year":"2019"},{"issue":"2","key":"pone.0350009.ref082","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.drudis.2015.12.007","article-title":"In silico methods to address polypharmacology: current status, applications and future perspectives","volume":"21","author":"A Lavecchia","year":"2016","journal-title":"Drug Discov Today"},{"key":"pone.0350009.ref083","doi-asserted-by":"crossref","first-page":"1362456","DOI":"10.3389\/fddsv.2024.1362456","article-title":"Integrative computational approaches for discovery and evaluation of lead compound for drug design","volume":"4","author":"U Naithani","year":"2024","journal-title":"Front Drug Discov"},{"key":"pone.0350009.ref084","doi-asserted-by":"crossref","first-page":"733","DOI":"10.3389\/fphar.2020.00733","article-title":"Discovering anti-cancer drugs via computational methods","volume":"11","author":"W Cui","year":"2020","journal-title":"Front Pharmacol"},{"issue":"9","key":"pone.0350009.ref085","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures","volume":"58","author":"DEV Pires","year":"2015","journal-title":"J Med Chem"},{"key":"pone.0350009.ref086","doi-asserted-by":"crossref","first-page":"1189786","DOI":"10.3389\/fmicb.2023.1189786","article-title":"Target specific inhibition of West Nile virus envelope glycoprotein and methyltransferase using phytocompounds: an in silico strategy leveraging molecular docking and dynamics simulation","volume":"14","author":"S Akash","year":"2023","journal-title":"Front Microbiol"},{"issue":"15","key":"pone.0350009.ref087","doi-asserted-by":"crossref","first-page":"5799","DOI":"10.1080\/07391102.2020.1787226","article-title":"Screening of phytochemical compounds of Tinospora cordifolia for their inhibitory activity on SARS-CoV-2: an in silico study","volume":"39","author":"S Krupanidhi","year":"2021","journal-title":"J Biomol Struct Dyn"},{"issue":"47","key":"pone.0350009.ref088","doi-asserted-by":"crossref","first-page":"29267","DOI":"10.1039\/D1RA05268C","article-title":"Anti-SARS-CoV-2 activities of tanshinone IIA, carnosic acid, rosmarinic acid, salvianolic acid, baicalein, and glycyrrhetinic acid between computational and in vitro insights","volume":"11","author":"D Elebeedy","year":"2021","journal-title":"RSC Adv"},{"issue":"8","key":"pone.0350009.ref089","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.1080\/07391102.2020.1753579","article-title":"Computational discovery of plant-based inhibitors against human carbonic anhydrase IX and molecular dynamics simulation","volume":"39","author":"S Mahmud","year":"2021","journal-title":"J Biomol Struct Dyn"},{"issue":"4","key":"pone.0350009.ref090","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s00726-007-0015-4","article-title":"Strong and weak hydrogen bonds in protein-ligand complexes of kinases: a comparative study","volume":"34","author":"SK Panigrahi","year":"2008","journal-title":"Amino Acids"},{"issue":"36","key":"pone.0350009.ref091","doi-asserted-by":"crossref","first-page":"22129","DOI":"10.1039\/D2CP03446H","article-title":"Deciphering the binding mechanism of inhibitors of the SARS-CoV-2 main protease through multiple replica accelerated molecular dynamics simulations and free energy landscapes","volume":"24","author":"M Li","year":"2022","journal-title":"Phys Chem Chem Phys"},{"issue":"5","key":"pone.0350009.ref092","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1517\/17460441.2015.1032936","article-title":"The MM\/PBSA and MM\/GBSA methods to estimate ligand-binding affinities","volume":"10","author":"S Genheden","year":"2015","journal-title":"Expert Opin Drug Discov"}],"container-title":["PLOS 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