Reviewing HIV-1 Gag Mutations in Protease Inhibitors Resistance: Insights for Possible Novel Gag Inhibitor Designs

Reviewing HIV-1 Gag Mutations in Protease Inhibitors Resistance: Insights for Possible Novel Gag Inhibitor Designs

Molecules

10.3390/molecules24183243

https://doi.org/10.3390/molecules24183243

Chinh Tran-To Su, Darius Wen-Shuo Koh, Samuel Ken-En Gan

HIV-1 Gag, Gag inhibitors, protease, protease inhibitors, drug resistance mutations, drug design

06 September 2019

Su, C. .-T.; Koh, D. .-S.; Gan, S. .-E. Reviewing HIV-1 Gag Mutations in Protease Inhibitors Resistance: Insights for Possible Novel Gag Inhibitor Designs. Molecules 2019, 24, 3243

HIV protease inhibitors against the viral protease are often hampered by drug resistance mutations in protease and in the viral substrate Gag. To overcome this drug resistance and inhibit viral maturation, targeting Gag alongside protease rather than targeting protease alone may be more efficient. In order to successfully inhibit Gag, understanding of its drug resistance mutations and the elicited structural changes on protease binding needs to be investigated. While mutations on Gag have already been mapped to protease inhibitor resistance, there remain many mutations, particularly the non-cleavage mutations, that are not characterized. Through structural studies to unravel how Gag mutations contributes to protease drug resistance synergistically, it is thus possible to glean insights to design novel Gag inhibitors. In this review, we discuss the structural role of both novel and previously reported Gag mutations in PI resistance, and how new Gag inhibitors can be designed

http://creativecommons.org/licenses/by/4.0/

The research is supported by core fund of the Antibody and Product Development (APD) Lab, Bioinformatics Institute, A*STAR.

https://oar.a-star.edu.sg/communities-collections/articles/15421

1420-3049

Bioinformatics Institute