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• W2477687688 endingPage "9508" @default.
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• W2477687688 abstract "ABSTRACT The emergence of transmissible HIV-1 strains with resistance to antiretroviral drugs highlights a continual need for new therapies. Here we describe a novel acylguanidine-containing compound, 1-(2-(azepan-1-yl)nicotinoyl)guanidine (or SM111), that inhibits in vitro replication of HIV-1, including strains resistant to licensed protease, reverse transcriptase, and integrase inhibitors, without major cellular toxicity. At inhibitory concentrations, intracellular p24 Gag production was unaffected, but virion release (measured as extracellular p24 Gag ) was reduced and virion infectivity was substantially impaired, suggesting that SM111 acts at a late stage of viral replication. SM111-mediated inhibition of HIV-1 was partially overcome by a Vpu I17R mutation alone or a Vpu W22* truncation in combination with Env N136Y. These mutations enhanced virion infectivity and Env expression on the surface of infected cells in the absence and presence of SM111 but also impaired Vpu's ability to downregulate CD4 and BST2/tetherin. Taken together, our results support acylguanidines as a class of HIV-1 inhibitors with a distinct mechanism of action compared to that of licensed antiretrovirals. Further research on SM111 and similar compounds may help to elucidate knowledge gaps related to Vpu's role in promoting viral egress and infectivity. IMPORTANCE New inhibitors of HIV-1 replication may be useful as therapeutics to counteract drug resistance and as reagents to perform more detailed studies of viral pathogenesis. SM111 is a small molecule that blocks the replication of wild-type and drug-resistant HIV-1 strains by impairing viral release and substantially reducing virion infectivity, most likely through its ability to prevent Env expression at the infected cell surface. Partial resistance to SM111 is mediated by mutations in Vpu and/or Env, suggesting that the compound affects host/viral protein interactions that are important during viral egress. Further characterization of SM111 and similar compounds may allow more detailed pharmacological studies of HIV-1 egress and provide opportunities to develop new treatments for HIV-1." @default.
• W2477687688 created "2016-08-23" @default.
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• W2477687688 date "2016-10-15" @default.
• W2477687688 modified "2023-10-18" @default.
• W2477687688 title "Novel Acylguanidine-Based Inhibitor of HIV-1" @default.
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• W2477687688 cites W1659719610 @default.
• W2477687688 cites W1793297159 @default.
• W2477687688 cites W1794879226 @default.
• W2477687688 cites W1814017524 @default.
• W2477687688 cites W1965489457 @default.
• W2477687688 cites W1965706772 @default.
• W2477687688 cites W1968140392 @default.
• W2477687688 cites W1968781739 @default.
• W2477687688 cites W1986384364 @default.
• W2477687688 cites W1989321543 @default.
• W2477687688 cites W1996076186 @default.
• W2477687688 cites W2009881602 @default.
• W2477687688 cites W2010458160 @default.
• W2477687688 cites W2012182557 @default.
• W2477687688 cites W2014098988 @default.
• W2477687688 cites W2014283693 @default.
• W2477687688 cites W2014893636 @default.
• W2477687688 cites W2017980922 @default.
• W2477687688 cites W2022128427 @default.
• W2477687688 cites W2030412425 @default.
• W2477687688 cites W2036270340 @default.
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• W2477687688 cites W2043597268 @default.
• W2477687688 cites W2047452261 @default.
• W2477687688 cites W2054348098 @default.
• W2477687688 cites W2062019922 @default.
• W2477687688 cites W2063658549 @default.
• W2477687688 cites W2066891535 @default.
• W2477687688 cites W2073327383 @default.
• W2477687688 cites W2075537868 @default.
• W2477687688 cites W2082437981 @default.
• W2477687688 cites W2091508129 @default.
• W2477687688 cites W2093244211 @default.
• W2477687688 cites W2094373128 @default.
• W2477687688 cites W2094800705 @default.
• W2477687688 cites W2097905379 @default.
• W2477687688 cites W2099164564 @default.
• W2477687688 cites W2103731776 @default.
• W2477687688 cites W2104816728 @default.
• W2477687688 cites W2108558787 @default.
• W2477687688 cites W2112507995 @default.
• W2477687688 cites W2114288367 @default.
• W2477687688 cites W2115395564 @default.
• W2477687688 cites W2118000026 @default.
• W2477687688 cites W2119208302 @default.
• W2477687688 cites W2123027509 @default.
• W2477687688 cites W2125153161 @default.
• W2477687688 cites W2132537853 @default.
• W2477687688 cites W2137222057 @default.
• W2477687688 cites W2139927157 @default.
• W2477687688 cites W2146478787 @default.
• W2477687688 cites W2147046090 @default.
• W2477687688 cites W2152113918 @default.
• W2477687688 cites W2160207721 @default.
• W2477687688 cites W2167010970 @default.
• W2477687688 cites W2187915469 @default.
• W2477687688 cites W2198233536 @default.
• W2477687688 cites W2280540363 @default.
• W2477687688 cites W2301676073 @default.
• W2477687688 cites W2320400608 @default.
• W2477687688 cites W2325599557 @default.
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• W2477687688 doi "https://doi.org/10.1128/jvi.01107-16" @default.
• W2477687688 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5044834" @default.
• W2477687688 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27512074" @default.
• W2477687688 hasPublicationYear "2016" @default.
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