A dynamic target-based pharmacophoric model mapping the CD4 binding site on HIV-1 gp120 to identify new inhibitors of gp120-CD4 protein-protein interactions.
A dynamic target-based pharmacophoric model mapping the CD4 binding site on HIV-1 gp120 was built and used to identify new hits able to inhibit gp120-CD4 protein-protein interactions. Two compounds showed micromolar inhibition of HIV-1 replication in cells attributable to an interference with the entry step of infection, by direct interaction with gp120. Inactivity of compounds toward a M475I strain suggested specific contacts with the Phe43 cavity of gp120.
Caporuscio
Fabiana
F
Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via Alcide de Gasperi, 2, 53100 Siena, Italy.
Tafi
Andrea
A
González
Emmanuel
E
Manetti
Fabrizio
F
Esté
José A
JA
Botta
Maurizio
M
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000633:toxicity; D001665:Binding Sites; D015704:CD4 Antigens / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D003198:Computer Simulation; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008956:Models, Chemical; D010666:Phenylpropionates / Q000737:chemistry* / Q000633:toxicity; D010797:Phthalimides / Q000737:chemistry* / Q000633:toxicity; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D010666:Phenylpropionates; D010797:Phthalimides