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HIV-1 gp120 as a therapeutic target: navigating a moving labyrinth.

Publication ,  Journal Article
Acharya, P; Lusvarghi, S; Bewley, CA; Kwong, PD
Published in: Expert Opin Ther Targets
June 2015

INTRODUCTION: The HIV-1 gp120 envelope (Env) glycoprotein mediates attachment of virus to human target cells that display requisite receptors, CD4 and co-receptor, generally CCR5. Despite high-affinity interactions with host receptors and proof-of-principle by the drug maraviroc that interference with CCR5 provides therapeutic benefit, no licensed drug currently targets gp120. AREAS COVERED: An overview of the role of gp120 in HIV-1 entry and of sites of potential gp120 vulnerability to therapeutic inhibition is presented. Viral defenses that protect these sites and turn gp120 into a moving labyrinth are discussed together with strategies for circumventing these defenses to allow therapeutic targeting of gp120 sites of vulnerability. EXPERT OPINION: The gp120 envelope glycoprotein interacts with host proteins through multiple interfaces and has conserved structural features at these interaction sites. In spite of this, targeting gp120 for therapeutic purposes is challenging. Env mechanisms that have evolved to evade the humoral immune response also shield it from potential therapeutics. Nevertheless, substantial progress has been made in understanding HIV-1 gp120 structure and its interactions with host receptors, and in developing therapeutic leads that potently neutralize diverse HIV-1 strains. Synergies between advances in understanding, needs for therapeutics against novel viral targets and characteristics of breadth and potency for a number of gp120-targetting lead molecules bodes well for gp120 as a HIV-1 therapeutic target.

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Published In

Expert Opin Ther Targets

DOI

EISSN

1744-7631

Publication Date

June 2015

Volume

19

Issue

6

Start / End Page

765 / 783

Location

England

Related Subject Headings

  • Triazoles
  • Receptors, CCR5
  • Oncology & Carcinogenesis
  • Molecular Targeted Therapy
  • Maraviroc
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp120
  • Drug Design
 

Citation

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Acharya, P., Lusvarghi, S., Bewley, C. A., & Kwong, P. D. (2015). HIV-1 gp120 as a therapeutic target: navigating a moving labyrinth. Expert Opin Ther Targets, 19(6), 765–783. https://doi.org/10.1517/14728222.2015.1010513
Acharya, Priyamvada, Sabrina Lusvarghi, Carole A. Bewley, and Peter D. Kwong. “HIV-1 gp120 as a therapeutic target: navigating a moving labyrinth.Expert Opin Ther Targets 19, no. 6 (June 2015): 765–83. https://doi.org/10.1517/14728222.2015.1010513.
Acharya P, Lusvarghi S, Bewley CA, Kwong PD. HIV-1 gp120 as a therapeutic target: navigating a moving labyrinth. Expert Opin Ther Targets. 2015 Jun;19(6):765–83.
Acharya, Priyamvada, et al. “HIV-1 gp120 as a therapeutic target: navigating a moving labyrinth.Expert Opin Ther Targets, vol. 19, no. 6, June 2015, pp. 765–83. Pubmed, doi:10.1517/14728222.2015.1010513.
Acharya P, Lusvarghi S, Bewley CA, Kwong PD. HIV-1 gp120 as a therapeutic target: navigating a moving labyrinth. Expert Opin Ther Targets. 2015 Jun;19(6):765–783.

Published In

Expert Opin Ther Targets

DOI

EISSN

1744-7631

Publication Date

June 2015

Volume

19

Issue

6

Start / End Page

765 / 783

Location

England

Related Subject Headings

  • Triazoles
  • Receptors, CCR5
  • Oncology & Carcinogenesis
  • Molecular Targeted Therapy
  • Maraviroc
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp120
  • Drug Design