{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:34:11Z","timestamp":1789652051438,"version":"4.0.0"},"reference-count":61,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T00:00:00Z","timestamp":1598400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["RCA13100251124"],"award-info":[{"award-number":["RCA13100251124"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001323","name":"Poliomyelitis Research Foundation","doi-asserted-by":"publisher","award":["55293"],"award-info":[{"award-number":["55293"]}],"id":[{"id":"10.13039\/501100001323","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The process of viral integration into the host genome is an essential step of the HIV-1 life cycle. The viral integrase (IN) enzyme catalyzes integration. IN is an ideal therapeutic enzyme targeted by several drugs; raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG), and bictegravir (BIC) having been approved by the USA Food and Drug Administration (FDA). Due to high HIV-1 diversity, it is not well understood how specific naturally occurring polymorphisms (NOPs) in IN may affect the structure\/function and binding affinity of integrase strand transfer inhibitors (INSTIs). We applied computational methods of molecular modelling and docking to analyze the effect of NOPs on the full-length IN structure and INSTI binding. We identified 13 NOPs within the Cameroonian-derived CRF02_AG IN sequences and further identified 17 NOPs within HIV-1C South African sequences. The NOPs in the IN structures did not show any differences in INSTI binding affinity. However, linear regression analysis revealed a positive correlation between the Ki and EC50 values for DTG and BIC as strong inhibitors of HIV-1 IN subtypes. All INSTIs are clinically effective against diverse HIV-1 strains from INSTI treatment-na\u00efve populations. This study supports the use of second-generation INSTIs such as DTG and BIC as part of first-line combination antiretroviral therapy (cART) regimens, due to a stronger genetic barrier to the emergence of drug resistance.<\/jats:p>","DOI":"10.3390\/v12090936","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T09:05:37Z","timestamp":1598432737000},"page":"936","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Structural Comparison of Diverse HIV-1 Subtypes using Molecular Modelling and Docking Analyses of Integrase Inhibitors"],"prefix":"10.3390","volume":"12","author":[{"given":"Darren","family":"Isaacs","sequence":"first","affiliation":[{"name":"South African Medical Research Council Bioinformatics Unit, South African National Bioinformatics Institute, University of the Western Cape, Cape Town 8000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sello Given","family":"Mikasi","sequence":"additional","affiliation":[{"name":"Division of Medical Virology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Francie van Zijl Avenue, P.O. Box 241, Cape Town 8000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0934-9586","authenticated-orcid":false,"given":"Adetayo Emmanuel","family":"Obasa","sequence":"additional","affiliation":[{"name":"Division of Medical Virology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Francie van Zijl Avenue, P.O. Box 241, Cape Town 8000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George Mondinde","family":"Ikomey","sequence":"additional","affiliation":[{"name":"Centre for the Study and Control of Communicable Diseases (CSCCD), University of Yaound\u00e9 1, Yaound\u00e9 P.O. Box 8445, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6953-9771","authenticated-orcid":false,"given":"Sergey","family":"Shityakov","sequence":"additional","affiliation":[{"name":"Department of Psychiatry &amp; Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung 404, Taiwan"},{"name":"Department of Bioinformatics, University of W\u00fcrzburg, W\u00fcrzburg 97074, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben","family":"Cloete","sequence":"additional","affiliation":[{"name":"South African Medical Research Council Bioinformatics Unit, South African National Bioinformatics Institute, University of the Western Cape, Cape Town 8000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3259-1496","authenticated-orcid":false,"given":"Graeme Brendon","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Division of Medical Virology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Francie van Zijl Avenue, P.O. Box 241, Cape Town 8000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1056\/NEJMra1201533","article-title":"Response to the AIDS Pandemic\u2014A Global Health Model","volume":"368","author":"Piot","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12730","DOI":"10.1021\/acs.chemrev.6b00125","article-title":"Retroviral DNA Integration","volume":"116","author":"Lesbats","year":"2016","journal-title":"Chem. 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