Open AccessFunctional and Structural Characterization of 2-Amino-4-phenylthiazole Inhibitors of the HIV-1 Nucleocapsid Protein with Antiviral Activity
Author(s) -
Mattia Mori,
Alessandro Nucci,
Maria Chiara Dasso Lang,
Nicolas Humbert,
Christian Boudier,
François Debaene,
Sarah Cianférani,
Marjorie Catala,
Patricia Schult-Dietrich,
Ursula Dietrich,
Carine Tisné,
Yves Mély,
Maurizio Botta
Publication year - 2014
Publication title -
acs chemical biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.899
H-Index - 111
eISSN - 1554-8937
pISSN - 1554-8929
DOI - 10.1021/cb500316h
Subject(s) - nucleic acid , viral life cycle , viral replication , biology , human immunodeficiency virus (hiv) , amino acid , computational biology , biochemistry , chemistry , virus , virology
The nucleocapsid protein (NC) is a highly conserved protein in diverse HIV-1 subtypes that plays a central role in virus replication, mainly by interacting with conserved nucleic acid sequences. NC is considered a highly profitable drug target to inhibit multiple steps in the HIV-1 life cycle with just one compound, a unique property not shown by any of the other antiretroviral classes. However, most of NC inhibitors developed so far act through an unspecific and potentially toxic mechanism (zinc ejection) and are mainly being investigated as topical microbicides. In an effort to provide specific NC inhibitors that compete for the binding of nucleic acids to NC, here we combined molecular modeling, organic synthesis, biophysical studies, NMR spectroscopy, and antiviral assays to design, synthesize, and characterize an efficient NC inhibitor endowed with antiviral activity in vitro, a desirable property for the development of efficient antiretroviral lead compounds.