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A novel small-molecule inhibitor of HIV-1 entry

Authors Heredia A, Latinovic O, Barbault F, de Leeuw E

Received 27 May 2015

Accepted for publication 10 July 2015

Published 1 October 2015 Volume 2015:9 Pages 5469—5478


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Professor Shu-Feng Zhou

Alonso Heredia,1,3 Olga S Latinovic,2,3 Florent Barbault,4 Erik PH de Leeuw3,5

1Department of Medicine, 2Department of Microbiology and Immunology, 3Institute of Human Virology, University of Maryland Baltimore School of Medicine, Baltimore, MD, USA; 4Univ Paris Diderot, Sorbonne Paris Cité, ITODYS, UMRCNRS7086, Paris, France; 5Department of Biochemistry and Molecular Biology, University of Maryland Baltimore School of Medicine, Baltimore, MD, USA

Background: Antiretroviral therapy has transformed HIV-1 infection into a managed condition with near-normal life expectancy. However, a significant number of patients remain with limited therapeutic options due to HIV-1 resistance, side effects, or drug costs. Further, it is likely that current drugs will not retain efficacy, due to risks of side effects and transmitted resistance.
Results: We describe compound 5660386 (3-ethyl-2-[3-(1,3,3-trimethyl-1,3-dihydro-2H-indol-2-ylidene)-1-propen-1-yl]-1,3-benzothiazol-3-ium) as a novel inhibitor of HIV-1 entry. Compound 5660386 inhibits HIV-1 entry in cell lines and primary cells, binds to HIV-1 envelope protein, and inhibits the interaction of GP120 to CD4. Further, compound 5660386 showed a unique and broad-range activity against primary HIV-1 isolates from different subtypes and geographical areas.
Conclusion: Development of small-molecule entry inhibitors of HIV-1 such as 5660386 may lead to novel classes of anti-HIV-1 therapeutics. These inhibitors may be particularly effective against viruses resistant to current antiretroviral drugs and could have potential applications in both treatment and prevention.

Keywords: HIV-1, defensin, drug, entry, antiviral therapy, CD4

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