{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:05:37Z","timestamp":1789506337298,"version":"build-2803163510"},"reference-count":88,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology","doi-asserted-by":"publisher","award":["DST\/ICD\/BRICS\/Call-3\/HIV protease\/2019"],"award-info":[{"award-number":["DST\/ICD\/BRICS\/Call-3\/HIV protease\/2019"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Acquired immunodeficiency syndrome (AIDS) is a chronic disease condition caused by the human immunodeficiency virus (HIV). The widespread availability of highly active antiretroviral therapies has helped to control HIV. There are ten FDA-approved protease inhibitors (PIs) that are used as part of antiretroviral therapies in HIV treatment. Importantly, all these drugs are designed and developed against the protease (PR) from HIV subtype B. On the other hand, HIV-1 PR subtype C, which is the most dominant strain in countries including South Africa and India, has shown resistance to PIs due to its genetic diversity and varied mutations. The emergence of resistance is concerning because the virus continues to replicate despite treatment; hence, it is necessary to develop drugs specifically against subtype C. This review focuses on the origin, genetic diversity, and mutations associated with HIV-1 PR subtype C. Furthermore, computational studies performed on HIV-1 PR subtype C and mutations associated with its resistance to PIs are highlighted. Moreover, potential research gaps and future directions in the study of HIV-1 PR subtype C are discussed.<\/jats:p>","DOI":"10.3390\/v17060850","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T14:03:11Z","timestamp":1750082591000},"page":"850","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Integrative Computational Approaches for Understanding Drug Resistance in HIV-1 Protease Subtype C"],"prefix":"10.3390","volume":"17","author":[{"given":"Sankaran","family":"Venkatachalam","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisha","family":"Muralidharan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh","family":"Pandian","sequence":"additional","affiliation":[{"name":"Protein Structure-Function Research Laboratory, School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg 2000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1781-2115","authenticated-orcid":false,"given":"Yasien","family":"Sayed","sequence":"additional","affiliation":[{"name":"Protein Structure-Function Research Laboratory, School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg 2000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1776-4096","authenticated-orcid":false,"given":"M. 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