{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T05:59:10Z","timestamp":1784872750295,"version":"3.55.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:00:00Z","timestamp":1667347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Respiratory syncytial virus (RSV) infection is one of the three most common causes of death in the infants, pre-schoolers, immunocompromised patients and elderly individuals due to many complications and lack of specific treatment. During RSV infection, the fusion protein (F protein) mediates the fusion of the virus envelope with the host cell membrane. Therefore, the F protein is an effective target for viral inhibition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We identified potential small-molecule inhibitors against RSV-F protein for the treatment of RSV infection using virtual screening and molecular dynamics (MD) simulations. The CCK8 assay was used to determine the cytotoxicity and quantitative RT\u2013PCR and indirect fluorescence assay (IFA) were used to determine the viral replication and RSV-induced inflammation in vitro. An RSV-infected mouse model was established, and viral replication was assayed using real-time quantitative PCR and IFA. Virus-induced complications were also examined using histopathological analysis, airway resistance and the levels of IL-1\u03b2, IL-6 and TNF-\u03b1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The top three potential inhibitors against the RSV-F protein were screened from the FDA-approved drug database. Z65, Z85 and Z74 significantly inhibited viral replication and RSV-induced inflammation. They also significantly alleviated RSV infection and RSV-induced complications in vivo. Z65 and Z85 had no cytotoxicity and better anti-RSV effects than Z74.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Z65 and Z85 may be suitable candidates for the treatment of RSV and serve as the basis for the development of new drugs.<\/jats:p><\/jats:sec>","DOI":"10.1093\/jac\/dkac370","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T17:17:48Z","timestamp":1667409468000},"page":"169-179","source":"Crossref","is-referenced-by-count":10,"title":["The antiviral efficacies of small-molecule inhibitors against respiratory syncytial virus based on the F protein"],"prefix":"10.1093","volume":"78","author":[{"given":"Pei","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Xiangya School of Medicine, Central South University , Changsha 410078, Hunan , China"},{"name":"Second Department of Laboratory, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University) , Changsha, Hunan 410006 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinglang","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Xiangya School of Medicine, Central South University , Changsha 410078, Hunan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Xiangya School of Medicine, Central South University , Changsha 410078, Hunan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongxiang","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Xiangya School of Medicine, Central South University , Changsha 410078, Hunan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ousman","family":"Bajinka","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Xiangya School of Medicine, Central South University , Changsha 410078, Hunan , China"},{"name":"School of Basic Medical Sciences, China-Africa Research Centre of Infectious Diseases, Central South University , Changsha 410078, Hunan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Xiangya School of Medicine, Central South University , Changsha 410078, Hunan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurong","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Xiangya School of Medicine, Central South University , Changsha 410078, Hunan , China"},{"name":"School of Basic Medical Sciences, China-Africa Research Centre of Infectious Diseases, Central South University , Changsha 410078, Hunan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,11,2]]},"reference":[{"key":"2023010801143585800_dkac370-B1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/s41579-019-0149-x","article-title":"Respiratory syncytial virus entry and how to block it","volume":"17","author":"Battles","year":"2019","journal-title":"Nat Rev Microbiol"},{"key":"2023010801143585800_dkac370-B2","doi-asserted-by":"crossref","first-page":"e13651","DOI":"10.1111\/pai.13651","article-title":"Dispersion and utilization of lipid droplets mediates respiratory syncytial virus-induced airway hyperresponsiveness","volume":"33","author":"Dai","year":"2021","journal-title":"Pediatr Allergy Immunol"},{"key":"2023010801143585800_dkac370-B3","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.medmal.2018.01.008","article-title":"Respiratory syncytial virus infection in elderly adults","volume":"48","author":"Haber","year":"2018","journal-title":"Med Mal Infect"},{"key":"2023010801143585800_dkac370-B4","doi-asserted-by":"crossref","first-page":"ofaa546","DOI":"10.1093\/ofid\/ofaa546","article-title":"Respiratory syncytial virus infection: its propensity for bacterial coinfection and related mortality in elderly adults","volume":"7","author":"Godefroy","year":"2020","journal-title":"Open Forum Infect Dis"},{"key":"2023010801143585800_dkac370-B5","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1080\/1040841X.2021.1960483","article-title":"Lung-brain axis","volume":"48","author":"Bajinka","year":"2021","journal-title":"Crit Rev Microbiol"},{"key":"2023010801143585800_dkac370-B6","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/jnc.14936","article-title":"Respiratory syncytial virus tropism for olfactory sensory neurons in mice","volume":"155","author":"Bryche","year":"2020","journal-title":"J Neurochem"},{"key":"2023010801143585800_dkac370-B7","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/S0140-6736(17)32152-9","article-title":"Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the global burden of disease study 2016","volume":"390","author":"GBD 2016 Causes of Death Collaborators","year":"2017","journal-title":"Lancet"},{"key":"2023010801143585800_dkac370-B8","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1111\/irv.12503","article-title":"The antiviral effects of RSV fusion inhibitor, MDT-637, on clinical isolates, vs its achievable concentrations in the human respiratory tract and comparison to ribavirin","volume":"11","author":"Kim","year":"2017","journal-title":"Influenza Other Respir Viruses"},{"key":"2023010801143585800_dkac370-B9","doi-asserted-by":"crossref","first-page":"e1005554","DOI":"10.1371\/journal.ppat.1005554","article-title":"Antigenic fingerprinting following primary RSV infection in young children identifies novel antigenic sites and reveals unlinked evolution of human antibody repertoires to fusion and attachment glycoproteins","volume":"12","author":"Fuentes","year":"2016","journal-title":"PLoS Pathog"},{"key":"2023010801143585800_dkac370-B10","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1128\/CMR.00010-16","article-title":"Respiratory syncytial virus: infection, detection, and new options for prevention and treatment","volume":"30","author":"Griffiths","year":"2017","journal-title":"Clin Microbiol Rev"},{"key":"2023010801143585800_dkac370-B11","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":"Mazur","year":"2015","journal-title":"Lancet Respir Med"},{"key":"2023010801143585800_dkac370-B12","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.3389\/fimmu.2019.01675","article-title":"Biology of infection and disease pathogenesis to guide RSV vaccine development","volume":"10","author":"Boyoglu-Barnum","year":"2019","journal-title":"Front Immunol"},{"key":"2023010801143585800_dkac370-B13","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.jbiotec.2020.10.014","article-title":"Development of a high yielding bioprocess for a pre-fusion RSV subunit vaccine","volume":"325","author":"Chen","year":"2021","journal-title":"J Biotechnol"},{"key":"2023010801143585800_dkac370-B14","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.drudis.2018.11.022","article-title":"The drug repurposing landscape from 2012 to 2017: evolution, challenges, and possible solutions","volume":"24","author":"Polamreddy","year":"2019","journal-title":"Drug Discov Today"},{"key":"2023010801143585800_dkac370-B15","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1021\/acs.jcim.5b00559","article-title":"ZINC 15\u2013ligand discovery for everyone","volume":"55","author":"Sterling","year":"2015","journal-title":"J Chem Inf Model"},{"key":"2023010801143585800_dkac370-B16","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1186\/1471-2105-13-S4-S2","article-title":"PyMod: sequence similarity searches, multiple sequence-structure alignments, and homology modeling within PyMOL","volume":"13","author":"Bramucci","year":"2012","journal-title":"BMC Bioinformatics"},{"key":"2023010801143585800_dkac370-B17","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s10822-010-9352-6","article-title":"Ligand docking and binding site analysis with PyMOL and Autodock\/Vina","volume":"24","author":"Seeliger","year":"2010","journal-title":"J Comput Aided Mol Des"},{"key":"2023010801143585800_dkac370-B18","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s00894-019-4011-x","article-title":"From GROMACS to LAMMPS: GRO2LAM: a converter for molecular dynamics software","volume":"25","author":"Thielemann","year":"2019","journal-title":"J Mol Model"},{"key":"2023010801143585800_dkac370-B19","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1002\/jcc.21726","article-title":"Combination of the CHARMM27 force field with united-atom lipid force fields","volume":"32","author":"Sapay","year":"2011","journal-title":"J Comput Chem"},{"key":"2023010801143585800_dkac370-B20","first-page":"1047","article-title":"Abnormal gene expression regulation mechanism of myeloid cell nuclear differentiation antigen in lung adenocarcinoma","volume":"11","author":"Tang","year":"2022","journal-title":"Biology (Basel)"},{"key":"2023010801143585800_dkac370-B21","doi-asserted-by":"crossref","first-page":"5885","DOI":"10.1002\/jmv.28061","article-title":"Lung-brain axis: metabolomics and pathological changes in lungs and brain of respiratory syncytial virus infected mice","volume":"94","author":"Mao","year":"2022","journal-title":"J Med Virol"},{"key":"2023010801143585800_dkac370-B22","doi-asserted-by":"crossref","first-page":"D1152","DOI":"10.1093\/nar\/gkaa861","article-title":"Dockcov2: a drug database against SARS-CoV-2","volume":"49","author":"Chen","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"2023010801143585800_dkac370-B23","doi-asserted-by":"crossref","first-page":"100094","DOI":"10.1016\/j.rechem.2020.100094","article-title":"In-silico drug repurposing study: amprenavir, enalaprilat, and plerixafor, potential drugs for destabilizing the SARS-CoV-2 S-protein-angiotensin-converting enzyme 2 complex","volume":"3","author":"Buitron-Gonzalez","year":"2021","journal-title":"Results Chem"},{"key":"2023010801143585800_dkac370-B24","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1099\/jmm.0.000959","article-title":"Respiratory syncytial virus promoted the differentiation of Th17 cells in airway microenvironment through activation of Notch-1\/Delta3","volume":"68","author":"Qin","year":"2019","journal-title":"J Med Microbiol"},{"key":"2023010801143585800_dkac370-B25","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.micpath.2019.03.019","article-title":"Involvement of epigenetic modification in epithelial immune responses during respiratory syncytial virus infection","volume":"130","author":"Caixia","year":"2019","journal-title":"Microb Pathog"},{"key":"2023010801143585800_dkac370-B26","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1007\/BF03161184","article-title":"Intramuscular ophthalmic homatropine vs. atropine to prevent lethality in rates with dichlorvos poisoning","volume":"2","author":"Bryant","year":"2006","journal-title":"J Med Toxicol"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/78\/1\/169\/48444515\/dkac370.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/78\/1\/169\/48444515\/dkac370.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T20:37:53Z","timestamp":1701203873000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/78\/1\/169\/6794070"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,2]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,11,2]]},"published-print":{"date-parts":[[2023,1,5]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkac370","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,1,5]]},"published":{"date-parts":[[2022,11,2]]}}}