The capsid protein of human immunodeficiency virus: designing inhibitors of capsid assembly.
The mature capsid of human immunodeficiency virus, HIV-1, is formed by the assembly of copies of a capsid protein (CA). The C-terminal domain of CA, CTD, is able to homodimerize and most of the dimerization interface is formed by a single alpha-helix from each monomer. Assembly of the HIV-1 capsid critically depends on CA-CA interactions, including CTD interaction with itself and with the CA N-terminal domain, NTD. This minireview reports on the search and the design of peptides and small organic compounds that are able to interact with the CTD and/or CA of HIV-1. Such molecules aim to disrupt and/or alter the oligomerization capability of CTD. The different peptides designed so far interact with CTD mainly via hydrophobic contacts with residues close or belonging to the interface between the dimerization helices. A CTD-binding organic compound also establishes hydrophobic contacts with regions involved in the interface between the NTD and CTD. These results open new venues for the development of new antiviral drugs that are able to interact with CA and/or its domains, hampering HIV-1 assembly and infection.
Neira
José L
JL
Instituto de Biología Molecular y Celular, Edificio Torregaitán, Universidad Miguel Hernández, Avda. del Ferrocarril s/n, 03202, Elche (Alicante), Spain. jlneira@umh.es
D019380:Anti-HIV Agents / Q000494:pharmacology*; D036022:Capsid Proteins / Q000737:chemistry*; D015195:Drug Design; D015497:HIV-1 / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D019151:Peptide Library; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D019065:Virus Assembly / Q000187:drug effects*
D019380:Anti-HIV Agents; D036022:Capsid Proteins; D019151:Peptide Library