Review: Peptide, Peptidomimetic and Small-molecule Drug Discovery Targeting HIV-1 Host-cell Attachment and Entry through gp120, gp41, CCR5 and CXCR4

• Published in: Chemical biology & drug design Vol. 67; no. 1; pp. 13 - 26
• Main Authors: Kazmierski, Wieslaw M, Kenakin, Terry P, Gudmundsson, Kristjan S
• Format: Journal Article
• Language: English
• Published: 01.01.2006
• Subjects: Human immunodeficiency virus 1
• ISSN: 1747-0277
• DOI: 10.1111/j.1747-0285.2005.00319.x

This review highlights selected examples of peptide, peptidomimetic and small-molecule drug discovery targeting HIV-1 to advance novel anti-HIV pharmaceuticals that inhibit initial stages of the viral cycle; namely, attachment and entry. Some of these approaches have culminated in the development of peptide-based drugs, while other have exploited peptides as enabling tools toward the identification of small-molecule lead compounds. Both of these conceptually different approaches have facilitated lead optimization of molecules with complementary and often surprising anti-HIV pharmacological properties, supporting their role in pharmaceutical development. Furthermore, such molecules enabled mechanistic elucidation of viral attachment and entry and provided additional insights toward achieving the desired drug profile.