{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:12:27Z","timestamp":1790017947159,"version":"4.0.1"},"reference-count":88,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T00:00:00Z","timestamp":1702944000000},"content-version":"vor","delay-in-days":27,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Scientific Foundation","award":["17-74-30019"],"award-info":[{"award-number":["17-74-30019"]}]},{"name":"Russian Scientific Foundation","award":["22-74-10098"],"award-info":[{"award-number":["22-74-10098"]}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["311031"],"award-info":[{"award-number":["311031"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019241","name":"CSC \u2013 IT Center for Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The coronavirus disease 2019 (COVID-19) pandemic has spurred a wide range of approaches to control and combat the disease. However, selecting an effective antiviral drug target remains a time-consuming challenge. Computational methods offer a promising solution by efficiently reducing the number of candidates. In this study, we propose a structure- and deep learning-based approach that identifies vulnerable regions in viral proteins corresponding to drug binding sites. Our approach takes into account the protein dynamics, accessibility and mutability of the binding site and the putative mechanism of action of the drug. We applied this technique to validate drug targeting toward severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein S. Our findings reveal a conformation- and oligomer-specific glycan-free binding site proximal to the receptor binding domain. This site comprises topologically important amino acid residues. Molecular dynamics simulations of Spike in complex with candidate drug molecules bound to the potential binding sites indicate an equilibrium shifted toward the inactive conformation compared with drug-free simulations. Small molecules targeting this binding site have the potential to prevent the closed-to-open conformational transition of Spike, thereby allosterically inhibiting its interaction with human angiotensin-converting enzyme 2 receptor. Using a pseudotyped virus-based assay with a SARS-CoV-2 neutralizing antibody, we identified a set of hit compounds that exhibited inhibition at micromolar concentrations.<\/jats:p>","DOI":"10.1093\/bib\/bbad459","type":"journal-article","created":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T17:01:35Z","timestamp":1703005295000},"source":"Crossref","is-referenced-by-count":12,"title":["Unraveling viral drug targets: a deep learning-based approach for the identification of potential binding sites"],"prefix":"10.1093","volume":"25","author":[{"given":"Petr","family":"Popov","sequence":"first","affiliation":[{"name":"Tetra-d , Rheinweg 9, Schaffhausen, 8200 , Switzerland"},{"name":"School of Science , Constructor University Bremen gGmbH, 28759, Bremen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Kalinin","sequence":"additional","affiliation":[{"name":"M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences , Moscow, 117997 , Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Buslaev","sequence":"additional","affiliation":[{"name":"Nanoscience Center and Department of Chemistry, University of Jyv\u00e4skyl\u00e4 , 40014, Jyv\u00e4skyl\u00e4 , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Kozlovskii","sequence":"additional","affiliation":[{"name":"Tetra-d , Rheinweg 9, Schaffhausen, 8200 , Switzerland"},{"name":"School of Science, Constructor University Bremen gGmbH , 28759, Bremen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Zaretckii","sequence":"additional","affiliation":[{"name":"Tetra-d , Rheinweg 9, Schaffhausen, 8200 , Switzerland"},{"name":"School of Science, Constructor University Bremen gGmbH , 28759, Bremen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Karlov","sequence":"additional","affiliation":[{"name":"School of Pharmacy , Medical Biology Centre, , Street, Belfast, BT9 7BL Northern Ireland , U.K"},{"name":"Queen\u2019s University Belfast , Medical Biology Centre, , Street, Belfast, BT9 7BL Northern Ireland , U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Gabibov","sequence":"additional","affiliation":[{"name":"M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences , Moscow, 117997 , Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Stepanov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road MB-10, La Jolla, 92037, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,12,18]]},"reference":[{"issue":"6","key":"2024011119370131500_ref1","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1056\/NEJMoa2023184","article-title":"Repurposed antiviral drugs for covid-19\u2014interim who solidarity trial results","volume":"384","author":"WHO Solidarity Trial Consortium","year":"2021","journal-title":"New Engl J Med"},{"issue":"6515","key":"2024011119370131500_ref2","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1126\/science.abd9909","article-title":"De novo design of picomolar sars-cov-2 miniprotein inhibitors","volume":"370","author":"Cao","year":"2020","journal-title":"Science"},{"issue":"9","key":"2024011119370131500_ref3","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1038\/nrd3439-c1","article-title":"Believe it or not: how much can we rely on published data on potential drug targets?","volume":"10","author":"Prinz","year":"2011","journal-title":"Nat Rev Drug Discov"},{"issue":"1","key":"2024011119370131500_ref4","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s12013-016-0769-y","article-title":"Can we rely on computational predictions to correctly identify ligand binding sites on novel protein drug targets? 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