Comprehending the Structure, Dynamics, and Mechanism of Action of Drug-Resistant HIV Protease

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2023 Mar 27

PMID 36969469

Authors

Avinash Dakshinamoorthy

Ananya Asmita

Sanjib Senapati

Affiliations

Soon will be listed here.

Abstract

Since the emergence of the Human Immunodeficiency Virus (HIV) in the 1980s, strategies to combat HIV-AIDS are continuously evolving. Among the many tested targets to tackle this virus, its protease enzyme (PR) was proven to be an attractive option that brought about numerous research publications and ten FDA-approved drugs to inhibit the PR activity. However, the drug-induced mutations in the enzyme made these small molecule inhibitors ineffective with prolonged usage. The research on HIV PR, therefore, remains a thrust area even today. Through this review, we reiterate the importance of understanding the various structural and functional components of HIV PR in redesigning the structure-based small molecule inhibitors. We also discuss at length the currently available FDA-approved drugs and how these drug molecules induced mutations in the enzyme structure. We then recapitulate the reported mechanisms on how these drug-resistant variants remain sufficiently active to cleave the natural substrates. We end with the future scope covering the recently proposed strategies that show promise to deal with the mutations.

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