HIV-1 gp120 as a therapeutic target: navigating a moving labyrinth

Expert Opinion on Therapeutic Targets
Priyamvada AcharyaPeter D Kwong

Abstract

The HIV-1 gp120 envelope (Env) glycoprotein mediates attachment of virus to human target cells that display requisite receptors, CD4 and co-receptor, generally CCR5. Despite high-affinity interactions with host receptors and proof-of-principle by the drug maraviroc that interference with CCR5 provides therapeutic benefit, no licensed drug currently targets gp120. An overview of the role of gp120 in HIV-1 entry and of sites of potential gp120 vulnerability to therapeutic inhibition is presented. Viral defenses that protect these sites and turn gp120 into a moving labyrinth are discussed together with strategies for circumventing these defenses to allow therapeutic targeting of gp120 sites of vulnerability. The gp120 envelope glycoprotein interacts with host proteins through multiple interfaces and has conserved structural features at these interaction sites. In spite of this, targeting gp120 for therapeutic purposes is challenging. Env mechanisms that have evolved to evade the humoral immune response also shield it from potential therapeutics. Nevertheless, substantial progress has been made in understanding HIV-1 gp120 structure and its interactions with host receptors, and in developing therapeutic leads that potently neutrali...Continue Reading

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Citations

Nov 26, 2015·Future Medicinal Chemistry·Irwin Chaiken, Adel A Rashad
Oct 27, 2016·Viruses·Sabrina Lusvarghi, Carole A Bewley
Jan 5, 2017·Journal of Molecular Modeling·Alexander M AndrianovAlexander V Tuzikov
Nov 9, 2018·Frontiers in Immunology·Jorge CarrilloJulià Blanco
Apr 16, 2021·Journal of Biomolecular Structure & Dynamics·Alexander M AndrianovAlexander V Tuzikov
May 8, 2021·Frontiers in Pharmacology·Huan-Jun LuZhi-Jun Zhang
Jul 10, 2020·International Immunopharmacology·Shahrzad AhangarzadehAbbas Alibakhshi
Jul 12, 2021·European Journal of Medicinal Chemistry·Ildar R IusupovAsim K Debnath
Oct 16, 2021·ACS Chemical Biology·Sachin S ShivatareChi-Huey Wong

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