{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T14:46:01Z","timestamp":1768488361145,"version":"3.49.0"},"posted":{"date-parts":[[2020,4,21]]},"group-title":"Microbiology","reference-count":32,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T00:00:00Z","timestamp":1587427200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2020,5,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Influenza A virus and coronavirus strains cause a mild to severe respiratory disease that can result in death. Although vaccines exist against circulating influenza A viruses, such vaccines are ineffective against emerging pandemic influenza A viruses. Currently, no vaccine exists against coronavirus infections, including pandemic SARS-CoV-2, the causative agent of the Coronavirus Disease 2019 (COVID-19). To combat these RNA virus infections, alternative antiviral strategies are needed. A key drug target is the viral RNA polymerase, which is responsible for viral RNA synthesis. In January 2020, the World Health Organisation identified enisamium as a candidate therapeutic against SARS-CoV-2. Enisamium is an isonicotinic acid derivative that is an inhibitor of multiple influenza B and A virus strains in cell culture and clinically approved in 11 countries. Here we show using\n                  <jats:italic>in vitro<\/jats:italic>\n                  assays that enisamium and its putative metabolite, VR17-04, inhibit the activity of the influenza virus and the SARS-CoV-2 RNA polymerase. VR17-04 displays similar efficacy against the SARS-CoV-2 RNA polymerase as the nucleotide analogue remdesivir triphosphate. These results suggest that enisamium is a broad-spectrum small molecule inhibitor of RNA virus RNA synthesis, and implicate it as a possible therapeutic option for treating SARS-CoV-2 infection. Unlike remdesivir, enisamium does not require intravenous administration which may be advantageous for the development of COVID-19 treatments outside a hospital setting.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Importance<\/jats:title>\n                  <jats:p>Influenza A virus and SARS-CoV-2 are respiratory viruses capable of causing pandemics, and the latter is responsible for the Coronavirus Disease 2019 (COVID-19) pandemic. Both viruses encode RNA polymerases which transcribe their RNA genomes and are important targets for antiviral drugs including remdesivir. Here, we show that the antiviral drug enisamium inhibits the RNA polymerases of both influenza A virus and SARS-CoV-2. Furthermore, we show that a putative metabolite of enisamium is a more potent inhibitor, inhibiting the SARS-CoV-2 RNA polymerase with similar efficiency to remdesivir. Our data offer insight into the mechanism of action for enisamium, and implicate it as a broad-spectrum antiviral which could be used in the treatment of SARS-CoV-2 infection.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2020.04.21.053017","type":"posted-content","created":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T07:15:16Z","timestamp":1587539716000},"source":"Crossref","is-referenced-by-count":14,"title":["Enisamium is a small molecule inhibitor of the influenza A virus and SARS-CoV-2 RNA polymerases"],"prefix":"10.64898","author":[{"given":"Alexander P","family":"Walker","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haitian","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy R","family":"Keown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Margitich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan M","family":"Grimes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3249-196X","authenticated-orcid":false,"given":"Ervin","family":"Fodor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5129-3953","authenticated-orcid":false,"given":"Aartjan J W","family":"te Velthuis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024080404321898000_2020.04.21.053017v2.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4529"},{"key":"2024080404321898000_2020.04.21.053017v2.2","unstructured":"Gorbalenya AE , Baker SC , Baric RS , de Groot RJ , Drosten C , Gulyaeva AA , Haagmans BL , Lauber C , Leontovich AM , Neuman BW , Penzar D , Perlman S , Poon LLM , Samborskiy D V. , Sidorov IA , Sola I , Ziebuhr J. 2020. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. Nature Research."},{"key":"2024080404321898000_2020.04.21.053017v2.3","doi-asserted-by":"crossref","unstructured":"Liu C , Zhou Q , Li Y , Garner L V. , Watkins SP , Carter LJ , Smoot J , Gregg AC , Daniels AD , Jervey S , Albaiu D. 2020. Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases. 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Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science.","DOI":"10.1126\/science.abb7498"},{"key":"2024080404321898000_2020.04.21.053017v2.12","doi-asserted-by":"crossref","unstructured":"Yin W , Mao C , Luan X , Shen D-D , Shen Q , Su H , Wang X , Zhou F , Zhao W , Gao M , Chang S , Xie Y-C , Tian G , Jiang H-W , Tao S-C , Shen J , Jiang Y , Jiang H , Xu Y , Zhang S , Zhang Y , Xu HE . 2020. Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science.","DOI":"10.1101\/2020.04.08.032763"},{"key":"2024080404321898000_2020.04.21.053017v2.13","doi-asserted-by":"crossref","unstructured":"Hillen HS , Kokic G , Farnung L , Dienemann C , Tegunov D , Cramer P. 2020. 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