GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile.
PMID: 34780263
2022
Antimicrobial agents and chemotherapy
Discussion: 2), A364V
Discussion: In vitro, GSK'254 inhibited p25 cleavage in WT virus but not virus expressing A364V.
Discussion: Overall, the improved GSK'254 antiviral profile is likely a result of its higher binding affinity and longer residence times once bound to Gag; conversely, its reduced ability to inhibit the replication of the A364V virus and its inability to inhibit in vitro cleavage of A364V VLP are likely due to its poorer affinity and extremely rapid dissociation from the A364V binding site.
Discussion: While the surrogate analog for GSK'254 dissociated slowly from a panel of polymorphic HIV-1 Gag VLPs (mean half-life, 344 +- 91 min), it dissociated rapidly from the A364V VLP.
Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study.
Result: There is limited volume in this pocket, and replacement of the alanine side chain methyl group in the WT protein with the larger isopropyl moiety in the A364V resistance mutant may destabilize the six-helix bundle by preventing optimal engagement of the adjacent CA/SP1 monomers via steric blockade, thus increasing the rate of HIV protease cleavage and the rate of dissociation of bound GSK795, as previously reported.
Table: A364A/V
Table: A364V/A
Table: A364V
Discussion: In addition to V362I and A364V, a number of secondary mutations were selected.
Discussion: These substitutions are close to ( PMID: 21864346
2011
Retrovirology
Result: In the two cultures where A364V was not selected, mutations V362I and V370A were observed respectively.
Table: A364V
Discussion: Both proteases that were tested (HXB2 and PR-2) processed substrate with mutation A364V one order of magnitude more effectively than substrate with a V362I mutation.
Discussion: Mutation A364V occurred most frequently and was associated with a completely resistant phenotype in all three protease backgrounds (HXB2, PR-1 and PR-2).
Discussion: This might explain the high levels of bevirimat resistance conferred b
High prevalence of natural polymorphisms in Gag (CA-SP1) associated with reduced response to Bevirimat, an HIV-1 maturation inhibitor.
Abstract: Mutations H358Y, L363F/M, A364V and A366T/V confer in-vitro resistance to bevirimat.
Phenotypic susceptibility to bevirimat in isolates from HIV-1-infected patients without prior exposure to bevirimat.
PMID: 20308382
2010
Antimicrobial agents and chemotherapy
Abstract: In contrast, none of the previously defined resistance-conferring mutations in Gag selected in vitro (H358Y, L363M, L363F, A364V, A366V, or A366T) were found to occur among the viruses that we analyzed.
Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice.
HIV mutation literature information.
PMID: 
2022
Antimicrobial agents and chemotherapy
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