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HIV‐1 Envelope Spike MPER: From a Vaccine Target to a New Druggable Pocket for Novel and Effective Fusion Inhibitors
Author(s) -
Luque Francisco Javier,
Camarasa MaríaJosé
Publication year - 2021
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000411
Subject(s) - druggability , human immunodeficiency virus (hiv) , lipid bilayer fusion , drug discovery , small molecule , virology , viral envelope , computational biology , nat , chemistry , biology , virus , biochemistry , computer science , gene , computer network
Here we highlight a sound and unique work reported by Chen and co‐workers entitled “HIV‐1 fusion inhibitors targeting the membrane‐proximal external region of Env spikes” (Xiao et al., Nat. Chem. Biol . 2020 , 16 , 529). In this article, the authors identify, by means of a clever antibody‐guided strategy, several small molecules as fusion inhibitors of HIV‐1 replication acting at the membrane proximal external region (MPER) of the HIV‐1 envelope (Env) spike. MPER, which was previously recognized as a vaccine target, emerges as a novel druggable target for the discovery of HIV‐1 fusion inhibitors. The compounds (exemplified by dequalinium and dequalinium‐inspired analogues) prevent the conformational changes of Env from the prefusion species to the intermediate states required for membrane fusion. This work not only paves the way to novel, specific and useful anti‐HIV‐1 inhibitors, but also discloses new therapeutic strategies against other infectious diseases.