{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:07:21Z","timestamp":1792076841824,"version":"4.4.0"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2016,5,10]],"date-time":"2016-05-10T00:00:00Z","timestamp":1462838400000},"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"],"DOI":"10.1371\/journal.pone.0154097","type":"journal-article","created":{"date-parts":[[2016,5,10]],"date-time":"2016-05-10T13:30:09Z","timestamp":1462887009000},"page":"e0154097","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":38,"title":["Biochemical Effect of Resistance Mutations against Synergistic Inhibitors of RSV RNA Polymerase"],"prefix":"10.1371","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8369-907X","authenticated-orcid":true,"given":"Jerome","family":"Deval","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Fung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah K.","family":"Stevens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul C.","family":"Jordan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Gromova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua S.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Dyatkina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Prhavc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian A.","family":"Symons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Beigelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,5,10]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/S0140-6736(10)60206-1","article-title":"Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis","volume":"375","author":"H Nair","year":"2010","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1001\/jama.289.2.179","article-title":"Mortality associated with influenza and respiratory syncytial virus in the United States","volume":"289","author":"WW Thompson","year":"2003","journal-title":"JAMA"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1056\/NEJMoa0804877","article-title":"The burden of respiratory syncytial virus infection in young children","volume":"360","author":"CB Hall","year":"2009","journal-title":"N Engl J Med"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/S2213-2600(15)00255-6","article-title":"Lower respiratory tract infection caused by respiratory syncytial virus: current management and new therapeutics","volume":"3","author":"NI Mazur","year":"2015","journal-title":"Lancet Respir Med"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1086\/651603","article-title":"Pharmacologic advances in the treatment and prevention of respiratory syncytial virus","volume":"50","author":"KM Empey","year":"2010","journal-title":"Clin Infect Dis"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1056\/NEJMoa1413275","article-title":"Activity of Oral ALS-008176 in a Respiratory Syncytial Virus Challenge Study","volume":"373","author":"JP DeVincenzo","year":"2015","journal-title":"N Engl J Med"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1021\/jm5017279","article-title":"Discovery of 4&apos;-chloromethyl-2&apos;-deoxy-3&apos;,5&apos;-di-O-isobutyryl-2&apos;-fluorocytidine (ALS-8176), a first-in-class RSV polymerase inhibitor for treatment of human respiratory syncytial virus infection","volume":"58","author":"G Wang","year":"2015","journal-title":"J Med Chem"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"e1004995","DOI":"10.1371\/journal.ppat.1004995","article-title":"Molecular Basis for the Selective Inhibition of Respiratory Syncytial Virus RNA Polymerase by 2&apos;-Fluoro-4&apos;-Chloromethyl-Cytidine Triphosphate","volume":"11","author":"J Deval","year":"2015","journal-title":"PLoS Pathog"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.cell.2015.06.018","article-title":"Structure of the L Protein of Vesicular Stomatitis Virus from Electron Cryomicroscopy","volume":"162","author":"B Liang","year":"2015","journal-title":"Cell"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1038\/nprot.2012.085","article-title":"Template-based protein structure modeling using the RaptorX web server","volume":"7","author":"M Kallberg","year":"2012","journal-title":"Nat Protoc"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"7786","DOI":"10.1128\/JVI.00530-15","article-title":"Respiratory Syncytial Virus Inhibitor AZ-27 Differentially Inhibits Different Polymerase Activities at the Promoter","volume":"89","author":"SL Noton","year":"2015","journal-title":"J Virol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"3867","DOI":"10.1128\/AAC.02540-14","article-title":"Characterization of a respiratory syncytial virus L protein inhibitor","volume":"58","author":"CL Tiong-Yip","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","article-title":"Drug combination studies and their synergy quantification using the Chou-Talalay method","volume":"70","author":"TC Chou","year":"2010","journal-title":"Cancer Res"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0065-2571(84)90007-4","article-title":"Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors","volume":"22","author":"TC Chou","year":"1984","journal-title":"Adv Enzyme Regul"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0166-3542(90)90001-N","article-title":"A three-dimensional model to analyze drug-drug interactions","volume":"14","author":"MN Prichard","year":"1990","journal-title":"Antiviral Res"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.imlet.2014.09.006","article-title":"Respiratory Syncytial Virus: pathology, therapeutic drugs and prophylaxis","volume":"162","author":"RS Gomez","year":"2014","journal-title":"Immunol Lett"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.coviro.2013.03.008","article-title":"The polymerase of negative-stranded RNA viruses","volume":"3","author":"B Morin","year":"2013","journal-title":"Curr Opin Virol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1128\/JVI.02107-07","article-title":"A conserved motif in region v of the large polymerase proteins of nonsegmented negative-sense RNA viruses that is essential for mRNA capping","volume":"82","author":"J Li","year":"2008","journal-title":"J Virol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.molcel.2006.11.013","article-title":"Unconventional mechanism of mRNA capping by the RNA-dependent RNA polymerase of vesicular stomatitis virus","volume":"25","author":"T Ogino","year":"2007","journal-title":"Mol Cell"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"3463","DOI":"10.1073\/pnas.0913083107","article-title":"Histidine-mediated RNA transfer to GDP for unique mRNA capping by vesicular stomatitis virus RNA polymerase","volume":"107","author":"T Ogino","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"6861","DOI":"10.1128\/AAC.03847-14","article-title":"Molecular and structural basis for the roles of hepatitis C virus polymerase NS5B amino acids 15, 223, and 321 in viral replication and drug resistance","volume":"58","author":"AM Lam","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"12334","DOI":"10.1128\/JVI.05639-11","article-title":"Hepatitis C virus nucleotide inhibitors PSI-352938 and PSI-353661 exhibit a novel mechanism of resistance requiring multiple mutations within replicon RNA","volume":"85","author":"AM Lam","year":"2011","journal-title":"J Virol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"E348","DOI":"10.1073\/pnas.1214924110","article-title":"NTP-mediated nucleotide excision activity of hepatitis C virus RNA-dependent RNA polymerase","volume":"110","author":"Z Jin","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"13471","DOI":"10.1073\/pnas.95.23.13471","article-title":"Unblocking of chain-terminated primer by HIV-1 reverse transcriptase through a nucleotide-dependent mechanism","volume":"95","author":"PR Meyer","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.antiviral.2004.12.002","article-title":"YM-53403, a unique anti-respiratory syncytial virus agent with a novel mechanism of action","volume":"65","author":"K Sudo","year":"2005","journal-title":"Antiviral Res"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"323","DOI":"10.2174\/1570162043351093","article-title":"Conformational changes in HIV-1 reverse transcriptase induced by nonnucleoside reverse transcriptase inhibitor binding","volume":"2","author":"N Sluis-Cremer","year":"2004","journal-title":"Curr HIV Res"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"18202","DOI":"10.1074\/jbc.M413410200","article-title":"Crystal structures of the RNA-dependent RNA polymerase genotype 2a of hepatitis C virus reveal two conformations and suggest mechanisms of inhibition by non-nucleoside inhibitors","volume":"280","author":"BK Biswal","year":"2005","journal-title":"J Biol Chem"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"e84808","DOI":"10.1371\/journal.pone.0084808","article-title":"Structural and regulatory elements of HCV NS5B polymerase\u2014beta-loop and C-terminal tail\u2014are required for activity of allosteric thumb site II inhibitors","volume":"9","author":"SE Boyce","year":"2014","journal-title":"PLoS One"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"6503","DOI":"10.1128\/JVI.00386-12","article-title":"Structure of hepatitis C virus polymerase in complex with primer-template RNA","volume":"86","author":"RT Mosley","year":"2012","journal-title":"J Virol"},{"key":"ref30","article-title":"Thumb Site 2 Inhibitors of Hepatitis C Viral RNA-Dependent RNA Polymerase Allosterically Block the Transition from Initiation to Elongation","author":"J Li","year":"2016","journal-title":"J Biol Chem"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"e1002980","DOI":"10.1371\/journal.ppat.1002980","article-title":"The respiratory syncytial virus polymerase has multiple RNA synthesis activities at the promoter","volume":"8","author":"SL Noton","year":"2012","journal-title":"PLoS Pathog"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.virol.2012.09.022","article-title":"A stabilized respiratory syncytial virus reverse genetics system amenable to recombination-mediated mutagenesis","volume":"434","author":"AL Hotard","year":"2012","journal-title":"Virology"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1128\/JVI.76.4.1663-1672.2002","article-title":"Mapping the transcription and replication promoters of respiratory syncytial virus","volume":"76","author":"R Fearns","year":"2002","journal-title":"J Virol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"10226","DOI":"10.1073\/pnas.0913065107","article-title":"Evidence that the polymerase of respiratory syncytial virus initiates RNA replication in a nontemplated fashion","volume":"107","author":"SL Noton","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014a visualization system for exploratory research and analysis","volume":"25","author":"EF Pettersen","year":"2004","journal-title":"J Comput Chem"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0154097","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T02:39:43Z","timestamp":1588991983000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0154097"}},"subtitle":[],"editor":[{"given":"John S","family":"Tregoning","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,5,10]]},"references-count":35,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2016,5,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0154097","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,10]]}}}