{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T20:57:06Z","timestamp":1777928226059,"version":"3.51.4"},"reference-count":44,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["OMICS: A Journal of Integrative Biology"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:p>\n                    The COVID-19 pandemic phase caused by the SARS-CoV-2 has ended, but the emergence of new variants continues to threaten public health. The public health toolbox for COVID-19 is in need of not only vaccines but also drug discovery against the SARS-CoV-2 virus, the causative agent for the ongoing COVID-19 infections. We report here an\n                    <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                    molecular docking and dynamics study that uncovered the interactions of 26 flexible heteroarotinoids (FHT18), which are a class of anti-cancer compounds, as potential inhibitors against all 24 SARS-CoV-2 proteins. Of the 624 docked complexes, 69 displayed binding energies between \u22129.0 and \u221211.6 kcal\/mol, indicating good to strong binding affinities. At least five of these compounds displayed excellent binding affinities against the nonstructural protein 2, papain-like protease, nonstructural protein 4 (Nsp4), proof-reading exoribonuclease, membrane protein, and nucleocapsid protein. Structure\u2013activity relationship (SAR) analyses of these results revealed that a urea linker in place of a thiourea linker, enhanced the hydrophobic side chains attached to the chromane unit, and a CF\n                    <jats:sub>3<\/jats:sub>\n                    or OCF\n                    <jats:sub>3<\/jats:sub>\n                    functional group attached to the benzene ring contributed to increased binding affinities. Further, the molecular dynamics simulation study of the best-docked complex FHT18-6c with Nsp4 remained stable for at least 200 ns, leading to decreased structural fluctuations and increased compactness of the binding site. In conclusion, FHT18-6c deserves further translational research to explore its potential for repurposing as a potent drug candidate to combat COVID-19. We also call for continued drug discovery efforts to enrich the public health toolbox for COVID-19.\n                  <\/jats:p>","DOI":"10.1089\/omi.2024.0205","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T04:32:56Z","timestamp":1744259576000},"page":"259-267","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Let\u2019s Not Neglect Drug Discovery to Combat COVID-19:\n                    <i>In Silico<\/i>\n                    Study of the Anti-Cancer Compounds Flexible Heteroarotinoids as Candidate Inhibitors Against SARS-CoV-2 Proteins"],"prefix":"10.1177","volume":"29","author":[{"given":"Sujan","family":"Timsina","sequence":"first","affiliation":[{"name":"Department of Physics, Oklahoma State University, Stillwater, Oklahoma, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masrur","family":"Akhter","sequence":"additional","affiliation":[{"name":"Department of Physics, Oklahoma State University, Stillwater, Oklahoma, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6638-4014","authenticated-orcid":false,"given":"Donghua H.","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Physics, Oklahoma State University, Stillwater, Oklahoma, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"e_1_3_5_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab294"},{"key":"e_1_3_5_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-0144"},{"key":"e_1_3_5_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.2c06384"},{"key":"e_1_3_5_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.848682"},{"key":"e_1_3_5_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-005-2901-5"},{"key":"e_1_3_5_7_1","doi-asserted-by":"publisher","DOI":"10.3949\/ccjm.87a.20047"},{"key":"e_1_3_5_8_1","unstructured":"Biovia DS. 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