Open AccessSmall-Molecule Inhibition of Viral Fusion Glycoproteins
Author(s) -
Han-Yuan Liu,
Priscilla L. Yang
Publication year - 2021
Publication title -
annual review of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.605
H-Index - 42
eISSN - 2327-0578
pISSN - 2327-056X
DOI - 10.1146/annurev-virology-022221-063725
Subject(s) - glycoprotein , lipid bilayer fusion , druggability , biology , small molecule , viral membrane , viral entry , drug discovery , microbiology and biotechnology , biochemistry , computational biology , biophysics , membrane , virology , viral replication , virus , viral envelope , gene
Viral fusion glycoproteins catalyze membrane fusion during viral entry. Unlike most enzymes, however, they lack a conventional active site in which formation or scission of a specific covalent bond is catalyzed. Instead, they drive the membrane fusion reaction by cojoining highly regulated changes in conformation to membrane deformation. Despite the challenges in applying inhibitor design approaches to these proteins, recent advances in knowledge of the structures and mechanisms of viral fusogens have enabled the development of small-molecule inhibitors of both class I and class II viral fusion proteins. Here, we review well-validated inhibitors, including their discovery, targets, and mechanism(s) of action, while highlighting mechanistic similarities and differences. Together, these examples make a compelling case for small-molecule inhibitors as tools for probing the mechanisms of viral glycoprotein-mediated fusion and for viral glycoproteins as druggable targets.