HIV-1 Envelope Spike MPER: From a Vaccine Target to a New Druggable Pocket for Novel and Effective Fusion Inhibitors |
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Authors: | Prof?Dr Francisco Javier Luque Prof?Dr María-José Camarasa |
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Affiliation: | 1. Departament de Nutrició, Ciències de l'Alimentació I Gastronomía, Institut de Biomedicina (IBUB) and Institut de Química Teórica I Computacional (IQTCUB), Facultat de Farmàcia i Ciències de l'Alimentació, Prat de la Riba 171, 08921 Santa Coloma de Gramenet, Spain;2. Instituto de Química Médica (IQM-CSIC), Consejo Superior de Investigaciones Científicas, Juan de la Cierva 6, 28006 Madrid, Spain |
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Abstract: | 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. |
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Keywords: | HIV-1 fusion inhibitors HIV-1 envelope spike antibody-guided strategy drug discovery small molecules |
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