{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T15:03:18Z","timestamp":1780066998864,"version":"3.54.0"},"reference-count":52,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T00:00:00Z","timestamp":1669334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"College of Health and Life Sciences, Hamad Bin Khalifa University"},{"name":"Qatar Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The recent global health emergency caused by the coronavirus disease 2019 (COVID-19) pandemic has taken a heavy toll, both in terms of lives and economies. Vaccines against the disease have been developed, but the efficiency of vaccination campaigns worldwide has been variable due to challenges regarding production, logistics, distribution and vaccine hesitancy. Furthermore, vaccines are less effective against new variants of the SARS-CoV-2 virus and vaccination-induced immunity fades over time. These challenges and the vaccines\u2019 ineffectiveness for the infected population necessitate improved treatment options, including the inhibition of the SARS-CoV-2 main protease (Mpro). Drug repurposing to achieve inhibition could provide an immediate solution for disease management. Here, we used structure-based virtual screening (SBVS) to identify natural products (from NP-lib) and FDA-approved drugs (from e-Drug3D-lib and Drugs-lib) which bind to the Mpro active site with high-affinity and therefore could be designated as potential inhibitors. We prioritized nine candidate inhibitors (e-Drug3D-lib: Ciclesonide, Losartan and Telmisartan; Drugs-lib: Flezelastine, Hesperidin and Niceverine; NP-lib: three natural products) and predicted their half maximum inhibitory concentration using DeepPurpose, a deep learning tool for drug\u2013target interactions. Finally, we experimentally validated Losartan and two of the natural products as in vitro Mpro inhibitors, using a bioluminescence resonance energy transfer (BRET)-based Mpro sensor. Our study suggests that existing drugs and natural products could be explored for the treatment of COVID-19.<\/jats:p>","DOI":"10.3390\/biom12121754","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T03:28:49Z","timestamp":1669606129000},"page":"1754","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Structure-Based Virtual Screening and Functional Validation of Potential Hit Molecules Targeting the SARS-CoV-2 Main Protease"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1140-883X","authenticated-orcid":false,"given":"Balasubramanian","family":"Moovarkumudalvan","sequence":"first","affiliation":[{"name":"Division of Genomics and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Education City, Doha P.O. Box 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupriya Madhukumar","family":"Geethakumari","sequence":"additional","affiliation":[{"name":"Division of Biological and Biomedical Sciences, College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Education City, Doha P.O. Box 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3144-4080","authenticated-orcid":false,"given":"Ramya","family":"Ramadoss","sequence":"additional","affiliation":[{"name":"Biological Sciences, Carnegie Mellon University\u2014Qatar, Qatar Foundation, Education City, Doha P.O. Box 24866, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9194-4127","authenticated-orcid":false,"given":"Kabir H.","family":"Biswas","sequence":"additional","affiliation":[{"name":"Division of Biological and Biomedical Sciences, College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Education City, Doha P.O. Box 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3429-3094","authenticated-orcid":false,"given":"Borbala","family":"Mifsud","sequence":"additional","affiliation":[{"name":"Division of Genomics and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Education City, Doha P.O. Box 34110, Qatar"},{"name":"William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S1473-3099(20)30120-1","article-title":"An Interactive Web-Based Dashboard to Track COVID-19 in Real Time","volume":"20","author":"Dong","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","first-page":"248","article-title":"An Updated Estimation of the Risk of Transmission of the Novel Coronavirus (2019-NCov)","volume":"5","author":"Tang","year":"2020","journal-title":"Infect. Dis. Model."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kautish, S., Peng, S.-L., and Obaid, A.J. (2021). 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