Peptide, peptidomimetic and small-molecule drug discovery targeting HIV-1 host-cell attachment and entry through gp120, gp41, CCR5 and CXCR4.
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.
Division of Chemistry MV CEDD, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA. wieslaw.m.kazmierski@gsk.com
Wieslaw M
WM
Kazmierski
Terry P
TP
Kenakin
Kristjan S
KS
Gudmundsson
D000595:Amino Acid Sequence; D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D015195:Drug Design; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019713:Receptors, CCR5 / Q000737:chemistry / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D019713:Receptors, CCR5; D019718:Receptors, CXCR4