{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:57:51Z","timestamp":1787029071414,"version":"build-2736575974"},"reference-count":58,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:00:00Z","timestamp":1661299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIAID","doi-asserted-by":"publisher","award":["R01-AI-161570"],"award-info":[{"award-number":["R01-AI-161570"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIAID","doi-asserted-by":"publisher","award":["R01-AI-132833"],"award-info":[{"award-number":["R01-AI-132833"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIAID","doi-asserted-by":"publisher","award":["R01AI148740"],"award-info":[{"award-number":["R01AI148740"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIAID","doi-asserted-by":"publisher","award":["R01-MH-116695"],"award-info":[{"award-number":["R01-MH-116695"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIAID","doi-asserted-by":"publisher","award":["2020\/00651-5"],"award-info":[{"award-number":["2020\/00651-5"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["R01-AI-161570"],"award-info":[{"award-number":["R01-AI-161570"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["R01-AI-132833"],"award-info":[{"award-number":["R01-AI-132833"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["R01AI148740"],"award-info":[{"award-number":["R01AI148740"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["R01-MH-116695"],"award-info":[{"award-number":["R01-MH-116695"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["2020\/00651-5"],"award-info":[{"award-number":["2020\/00651-5"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Viral resistance is a worldwide problem mitigating the effectiveness of antiviral drugs. Mutations in the drug-targeting proteins are the primary mechanism for the emergence of drug resistance. It is essential to identify the drug resistance mutations to elucidate the mechanism of resistance and to suggest promising treatment strategies to counter the drug resistance. However, experimental identification of drug resistance mutations is challenging, laborious and time-consuming. Hence, effective and time-saving computational structure-based approaches for predicting drug resistance mutations are essential and are of high interest in drug discovery research. However, these approaches are dependent on accurate estimation of binding free energies which indirectly correlate to the computational cost. Towards this goal, we developed a computational workflow to predict drug resistance mutations for any viral proteins where the structure is known. This approach can qualitatively predict the change in binding free energies due to mutations through residue scanning and Prime MM-GBSA calculations. To test the approach, we predicted resistance mutations in HIV-RT selected by (-)-FTC and demonstrated accurate identification of the clinical mutations. Furthermore, we predicted resistance mutations in HBV core protein for GLP-26 and in SARS-CoV-2 3CLpro for nirmatrelvir. Mutagenesis experiments were performed on two predicted resistance and three predicted sensitivity mutations in HBV core protein for GLP-26, corroborating the accuracy of the predictions.<\/jats:p>","DOI":"10.3390\/molecules27175413","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T23:48:58Z","timestamp":1661384938000},"page":"5413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Assessment of a Computational Approach to Predict Drug Resistance Mutations for HIV, HBV and SARS-CoV-2"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1601-256X","authenticated-orcid":false,"given":"Dharmeshkumar","family":"Patel","sequence":"first","affiliation":[{"name":"Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, 1760 Haygood Dr., Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzane K.","family":"Ono","sequence":"additional","affiliation":[{"name":"Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, 1760 Haygood Dr., Atlanta, GA 30322, USA"},{"name":"Department of Gastroenterology, University of S\u00e3o Paulo School of Medicine, Av. Dr. Arnaldo, 455, S\u00e3o Paulo 05403-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leda","family":"Bassit","sequence":"additional","affiliation":[{"name":"Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, 1760 Haygood Dr., Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran","family":"Verma","sequence":"additional","affiliation":[{"name":"Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, 1760 Haygood Dr., Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Amblard","sequence":"additional","affiliation":[{"name":"Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, 1760 Haygood Dr., Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond F.","family":"Schinazi","sequence":"additional","affiliation":[{"name":"Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, 1760 Haygood Dr., Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1126\/science.280.5371.1871","article-title":"Hiv treatment failure: Testing for HIV resistance in clinical practice","volume":"280","author":"Perrin","year":"1998","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4982","DOI":"10.1002\/jmv.26971","article-title":"Real-world re-treatment outcomes of direct-acting antiviral therapy failure in patients with chronic hepatitis C","volume":"93","author":"Elhence","year":"2021","journal-title":"J. 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