{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T18:06:31Z","timestamp":1778177191598,"version":"3.51.4"},"reference-count":68,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,5,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>Anti-HIV-1 antibodies capable of mediating ADCC are elicited by the majority of people with HIV-1 and preferentially target the \u201copen,\u201d CD4-bound conformation of HIV-1 envelope glycoproteins (Env). However, due to the \u201cclosed\u201d conformation sampled by unliganded HIV-1-Envs, these antibodies are ineffective at eliminating infected cells. BNM-III-170 is a small-molecule CD4-mimetic compound that binds the Phe43 cavity of the gp120 subunit of Env, forcing Env to \u201copen up,\u201d thus exposing epitopes targeted by CD4-induced (CD4i), ADCC-mediating antibodies. Here, we assessed the safety, pharmacokinetics, and biological activity of BNM-III-170 in uninfected and SHIV-AD8-EO-infected rhesus macaques (RMs). In uninfected RMs, single subcutaneous administrations of 3\u201336 mg\/kg BNM-III-170 were well-tolerated, with serum half-lives ranging from 3 to 6 h. In SHIV-infected RMs, four different regimens were evaluated: 2 \u00d7 36 mg\/kg daily, 1 \u00d7 24 mg\/kg, 3 \u00d7 36 mg\/kg every 7 days, and 3 \u00d7 36 mg\/kg every 3 days. While toxicity was observed with daily doses, all other regimens demonstrated reasonable safety profiles. No changes in plasma viral loads were observed in SHIV-infected RMs following any of the evaluated BNM-III-170 dosing regimens. However, plasma collected following BNM-III-170 administration was shown to have increased binding to infected cells and to sensitize SHIV AD8-EO virions to neutralization by otherwise non-neutralizing antibodies. In addition, the plasma of treated animals mediated ADCC in the presence of BNM-III-170. These results establish a well-tolerated BNM-III-170 dosing regimen in SHIV-infected RMs and serve as proof of concept for its biological activity in promoting the targeting of infected cells by CD4i ADCC-mediating antibodies. Thus, they inform future studies evaluating CD4mc treatment in ART-treated animals.<\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                A therapeutic regimen able to eradicate or functionally cure HIV-1 remains elusive and may require a \u201cshock-and-kill\u201d approach to reactivate and then purge the latent HIV-1 reservoir. The small-molecule CD4-mimetic compound BNM-III-170 has previously been shown to (i) sensitize HIV-1-infected cells to ADCC mediated by plasma from people with HIV-1 (PWH)\n                <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                and (ii) significantly delay the time to viral rebound following ART interruption when combined with anti-CoRBS + anti-cluster A Abs or plasma from PWH in humanized mice. To evaluate the use of BNM-III-170 as part of a kill approach, we characterized the safety, pharmacokinetics, and biological activity of BNM-III-170 in uninfected and SHIV-infected RMs. Our study identifies a tolerable BNM-III-170 dosing regimen in SHIV-infected RMs and provides insights into its antiviral activities; as such, it informs future studies evaluating the efficacy of BNM-III-170 in reducing the viral reservoir.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/jvi.00062-25","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T13:03:48Z","timestamp":1744031028000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Safety, pharmacokinetics, and biological activity of CD4-mimetic BNM-III-170 in SHIV-infected rhesus macaques"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2788-4585","authenticated-orcid":false,"given":"Elise G.","family":"Viox","sequence":"first","affiliation":[{"name":"Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University","place":["Atlanta, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9015-9589","authenticated-orcid":true,"given":"Jonathan","family":"Richard","sequence":"additional","affiliation":[{"name":"Centre de Recherche du CHUM","place":["Montr\u00e9al, Canada"]},{"name":"D\u00e9partement de Microbiologie, Infectiologie et Immunologie, Universit\u00e9 de Montr\u00e9al","place":["Montr\u00e9al, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"Andres G.","family":"Grandea","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison","place":["Madison, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University","place":["Atlanta, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin","family":"Harper","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University","place":["Atlanta, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Auger","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University","place":["Atlanta, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shilei","family":"Ding","sequence":"additional","affiliation":[{"name":"Centre de Recherche du 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