Chemokine receptors as new molecular targets for antiviral therapy

F. Santoro, L. Vassena, P. Lusso

Research output: Contribution to journalArticle

Abstract

Extraordinary advancements have been made over the past decade in our understanding of the molecular mechanism of human immunodeficiency virus (HIV) entry into cells. The external HIV envelope glycoprotein, gp120, sequentially interacts with two cellular receptor molecules, the CD4 glycoprotein and a chemokine receptor, such as CCR5 or CXCR4, leading to the activation of the fusogenic domain of the transmembrane viral glycoprotein, gp41, which changes its conformation to create a hairpin structure that eventually triggers fusion between the viral and cellular membranes. Each of these discrete steps in the viral entry process represents a potetial target for new antiviral agents. Current efforts to develop safe and effective HIV entry inhibitors are focused on naturally occurring proteins (e.g., chemokines, antibodies), engineered or modified derivatives of natural proteins (e.g., multimerized soluble CD4, gp41 - or chemokine - derived synthetic peptides), as well as small synthetic compounds obtained either by high-throughput screening of large compound libraries or by structure-guided rational design. The recent introduction in therapy of the first fusion inhibitor, the gp41-derived synthetic peptide T20, heralds a new era in the treatment of AIDS, which will hopefully lead to more effective multi-drug regimens with reduced adverse effects for the patients.

Original languageEnglish
Pages (from-to)17-29
Number of pages13
JournalNew Microbiologica
Volume27
Issue number2 SUPPL. 1
Publication statusPublished - 2004

Keywords

  • Antivirals
  • Chemokines
  • HIV
  • Receptors
  • Viral entry

ASJC Scopus subject areas

  • Microbiology (medical)
  • Microbiology

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  • Cite this

    Santoro, F., Vassena, L., & Lusso, P. (2004). Chemokine receptors as new molecular targets for antiviral therapy. New Microbiologica, 27(2 SUPPL. 1), 17-29.