|
Basic Characteristics of Mutations
|
|
Mutation Site
|
A364V |
|
Mutation Site Sentence
|
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. |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
Gag |
|
Standardized Encoding Gene
|
Gag
|
|
Genotype/Subtype
|
HIV-1 |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
HIV Infections
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
Mis |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
39459843
|
|
Title
|
Preclinical Profile of the HIV-1 Maturation Inhibitor VH3739937
|
|
Author
|
McAuliffe B,Falk P,Chen J,Chen Y,Sit SY,Swidorski J,Hartz RA,Xu L,Venables B,Sin N,Meanwell NA,Regueiro-Ren A,Wensel D,Hanumegowda U,Krystal M
|
|
Journal
|
Viruses
|
|
Journal Info
|
2024 Sep 24;16(10):1508
|
|
Abstract
|
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 (EC(50)) values = 5.0 nM. In multiple-cycle assays, viruses less susceptible to other MIs, including A364V, were inhibited at EC(50) values = 8.0 nM and maximal percent inhibition (MPI) values >/= 92%. However, VH-937 was less potent against A364V in single-cycle assays (EC(50), 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.
|
|
Sequence Data
|
-
|
|
|