{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:17:24Z","timestamp":1793146644161,"version":"4.5.0"},"reference-count":44,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ViiV Healthcare"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The HIV-1 maturation inhibitor (MI) VH3739937 (VH-937) inhibits cleavage between capsid and spacer peptide 1 and exhibits an oral half-life in humans compatible with once-weekly dosing. Here, the antiviral properties of VH-937 are described. VH-937 exhibited potent antiviral activity against all HIV-1 laboratory strains, clinical isolates, and recombinant viruses examined, with half-maximal effective concentration (EC50) values \u2264 5.0 nM. In multiple-cycle assays, viruses less susceptible to other MIs, including A364V, were inhibited at EC50 values \u2264 8.0 nM and maximal percent inhibition (MPI) values \u2265 92%. However, VH-937 was less potent against A364V in single-cycle assays (EC50, 32.0 nM; MPI, 57%) and A364V emerged in one of four resistance selection cultures. Other substitutions were selected by VH-937, although re-engineered viruses with these sequences were non-functional in multiple-cycle assays. Measured dissociation rates from wild-type and A364V-containing VLPs help explain resistance to the A364V mutation. Overall, the in vitro antiviral activity of VH-937 supports its continued development as a treatment for HIV-1.<\/jats:p>","DOI":"10.3390\/v16101508","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T03:49:46Z","timestamp":1727149786000},"page":"1508","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Preclinical Profile of the HIV-1 Maturation Inhibitor VH3739937"],"prefix":"10.3390","volume":"16","author":[{"given":"Brian","family":"McAuliffe","sequence":"first","affiliation":[{"name":"ViiV Healthcare, 36 East Industrial Road, Branford, CT 06405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Falk","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, 36 East Industrial Road, Branford, CT 06405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sing-Yuen","family":"Sit","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2123-1222","authenticated-orcid":false,"given":"Jacob","family":"Swidorski","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3880-6646","authenticated-orcid":false,"given":"Richard A.","family":"Hartz","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xu","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Venables","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ny","family":"Sin","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8857-1515","authenticated-orcid":false,"given":"Nicholas A.","family":"Meanwell","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2991-719X","authenticated-orcid":false,"given":"Alicia","family":"Regueiro-Ren","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7680-3895","authenticated-orcid":false,"given":"David","family":"Wensel","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, 36 East Industrial Road, Branford, CT 06405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umesh","family":"Hanumegowda","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, 36 East Industrial Road, Branford, CT 06405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8905-2584","authenticated-orcid":false,"given":"Mark","family":"Krystal","sequence":"additional","affiliation":[{"name":"ViiV Healthcare, 36 East Industrial Road, Branford, CT 06405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1093\/cid\/ciab583","article-title":"Transmitted drug resistance among human immunodeficiency virus (HIV)-1 diagnoses in the United States, 2014\u20132018","volume":"74","author":"McClung","year":"2022","journal-title":"Clin. 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