Remdesivir Derivative VV116 Is a Potential Broad-Spectrum Inhibitor of Both Human and Animal Coronaviruses

{ 'indexed': { 'date-parts': [[2023, 11, 26]], 'date-time': '2023-11-26T00:02:40Z', 'timestamp': 1700956960396}, 'reference-count': 37, 'publisher': 'MDPI AG', 'issue': '12', 'license': [ { 'start': { 'date-parts': [[2023, 11, 23]], 'date-time': '2023-11-23T00:00:00Z', 'timestamp': 1700697600000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'funder': [ { 'DOI': '10.13039/501100012166', 'name': 'National Key Research and Development Program of China', 'doi-asserted-by': 'publisher', 'award': ['2018YFE0204502 and 2018YFE0204503']}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'abstract': '<jats:p>Coronaviruses represent a significant threat to both human and animal health, ' 'encompassing a range of pathogenic strains responsible for illnesses, from the common cold to ' 'more severe diseases. VV116 is a deuterated derivative of Remdesivir with oral ' 'bioavailability that was found to potently inhibit SARS-CoV-2. In this work, we investigated ' 'the broad-spectrum antiviral activity of VV116 against a variety of human and animal ' 'coronaviruses. We examined the inhibitory effects of VV116 on the replication of the human ' 'coronaviruses HCoV-NL63, HCoV-229E, and HCoV-OC43, as well as the animal coronaviruses MHV, ' 'FIPV, FECV, and CCoV. The findings reveal that VV116 effectively inhibits viral replication ' 'across these strains without exhibiting cytotoxicity, indicating its potential for safe ' 'therapeutic use. Based on the results of a time-of-addition assay and an rNTP competitive ' 'inhibition assay, it is speculated that the inhibitory mechanism of VV116 against HCoV-NL63 ' 'is consistent with its inhibition of SARS-CoV-2. Our work presents VV116 as a promising ' 'candidate for broad-spectrum anti-coronavirus therapy, with implications for both human and ' 'animal health, and supports the expansion of its therapeutic applications as backed by ' 'detailed experimental data.</jats:p>', 'DOI': '10.3390/v15122295', 'type': 'journal-article', 'created': { 'date-parts': [[2023, 11, 23]], 'date-time': '2023-11-23T08:45:18Z', 'timestamp': 1700729118000}, 'page': '2295', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Remdesivir Derivative VV116 Is a Potential Broad-Spectrum Inhibitor of Both Human and Animal ' 'Coronaviruses', 'prefix': '10.3390', 'volume': '15', 'author': [ { 'given': 'Weiyong', 'family': 'Liu', 'sequence': 'first', 'affiliation': [ { 'name': 'Department of Laboratory Medicine, Tongji Hospital, Tongji ' 'Medical College, Huazhong University of Science and Technology, ' 'Wuhan 430030, China'}]}, { 'given': 'Min', 'family': 'Zhang', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Emergency Medicine, The Third People’s Hospital of ' 'Hubei Province, Wuhan 430033, China'}]}, { 'given': 'Chengxiu', 'family': 'Hu', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Laboratory Medicine, Tongji Hospital, Tongji ' 'Medical College, Huazhong University of Science and Technology, ' 'Wuhan 430030, China'}]}, { 'given': 'Huijuan', 'family': 'Song', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Laboratory Medicine, Tongji Hospital, Tongji ' 'Medical College, Huazhong University of Science and Technology, ' 'Wuhan 430030, China'}]}, { 'given': 'Yi', 'family': 'Mei', 'sequence': 'additional', 'affiliation': [ { 'name': 'State Key Laboratory of Virology, College of Life Sciences, ' 'Wuhan University, Wuhan 430072, China'}]}, { 'given': 'Yingle', 'family': 'Liu', 'sequence': 'additional', 'affiliation': [ { 'name': 'State Key Laboratory of Virology, College of Life Sciences, ' 'Wuhan University, Wuhan 430072, China'}]}, { 'ORCID': 'http://orcid.org/0000-0003-2868-1816', 'authenticated-orcid': False, 'given': 'Qi', 'family': 'Zhang', 'sequence': 'additional', 'affiliation': [ { 'name': 'State Key Laboratory of Virology, College of Life Sciences, ' 'Wuhan University, Wuhan 430072, China'}]}], 'member': '1968', 'published-online': {'date-parts': [[2023, 11, 23]]}, 'reference': [ { 'key': 'ref_1', 'doi-asserted-by': 'crossref', 'first-page': '1467', 'DOI': '10.1136/bmj.1.5448.1467', 'article-title': 'Cultivation of a Novel Type of Common-Cold Virus in Organ Cultures', 'volume': '1', 'author': 'Tyrrell', 'year': '1965', 'journal-title': 'Br. 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