{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:15:35Z","timestamp":1760148935054,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,18]],"date-time":"2023-06-18T00:00:00Z","timestamp":1687046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"US National Institute of General Medical Sciences (NIGMS)","award":["R01GM130950","IA-831472"],"award-info":[{"award-number":["R01GM130950","IA-831472"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["R01GM130950","IA-831472"],"award-info":[{"award-number":["R01GM130950","IA-831472"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002590","name":"American Lung Association Innovation Award","doi-asserted-by":"publisher","award":["R01GM130950","IA-831472"],"award-info":[{"award-number":["R01GM130950","IA-831472"]}],"id":[{"id":"10.13039\/100002590","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Respiratory Syncytial Virus (RSV) is the top cause of infant hospitalization globally, with no effective treatments available. Researchers have sought small molecules to target the RNA-dependent RNA Polymerase (RdRP) of RSV, which is essential for replication and transcription. Based on the cryo-EM structure of the RSV polymerase, in silico computational analysis including molecular docking and the protein-ligand simulation of a database, including 6554 molecules, is currently undergoing phases 1\u20134 of clinical trials and has resulted in the top ten repurposed compound candidates against the RSV polymerase, including Micafungin, Totrombopag, and Verubecestat. We performed the same procedure to evaluate 18 small molecules from previous studies and chose the top four compounds for comparison. Among the top identified repurposed compounds, Micafungin, an antifungal medication, showed significant inhibition and binding affinity improvements over current inhibitors such as ALS-8112 and Ribavirin. We also validated Micafungin\u2019s inhibition of the RSV RdRP using an in vitro transcription assay. These findings contribute to RSV drug development and hold promise for broad-spectrum antivirals targeting the non-segmented negative-sense (NNS) RNA viral polymerases, including those of rabies (RABV) and Ebola (EBOV).<\/jats:p>","DOI":"10.3390\/microorganisms11061608","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T01:31:14Z","timestamp":1687138274000},"page":"1608","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In Silico Identification and In Vitro Validation of Repurposed Compounds Targeting the RSV Polymerase"],"prefix":"10.3390","volume":"11","author":[{"given":"Eric","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6483-2208","authenticated-orcid":false,"given":"Seohyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Calderon","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongdong","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5617-9228","authenticated-orcid":false,"given":"Bo","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1099\/vir.0.81786-0","article-title":"Unravelling the complexities of respiratory syncytial virus RNA synthesis","volume":"87","author":"Cowton","year":"2006","journal-title":"J. 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