Open AccessA targeted covalent small molecule inhibitor of HIV-1 fusion
Author(s) -
Guangyuan Zhou,
Li He,
Kathy H. Li,
Cássio Cardoso Santos Pedroso,
Miriam Gochin
Publication year - 2021
Publication title -
chemical communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.837
H-Index - 333
eISSN - 1364-548X
pISSN - 1359-7345
DOI - 10.1039/d1cc01013a
Subject(s) - covalent bond , chemistry , fusion , residue (chemistry) , peptide , small molecule , glycoprotein , lysine , human immunodeficiency virus (hiv) , fusion protein , combinatorial chemistry , stereochemistry , biophysics , biochemistry , recombinant dna , biology , virology , amino acid , organic chemistry , philosophy , linguistics , gene
We describe a low molecular weight covalent inhibitor targeting a conserved lysine residue within the hydrophobic pocket of HIV-1 glycoprotein-41. The inhibitor bound selectively to the hydrophobic pocket and exhibited an order of magnitude enhancement of anti-fusion activity against HIV-1 compared to its non-covalent counterpart. The findings represent a significant advance in the quest to obtain non-peptide fusion inhibitors.