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Molecules 2018, 23(7), 1599; https://doi.org/10.3390/molecules23071599

Combining New Non-Nucleoside Reverse Transcriptase Inhibitors (RTIs) with AZT Results in Strong Synergism against Multi-RTI-Resistant HIV-1 Strains

1,2,†
,
2,†
,
3,†
,
1
,
1
,
2
,
4
and
2,5,*
1
College of Life Sciences, Hebei Agricultural University, Baoding 071001, China
2
Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China
3
Research Center of Chinese Jujube, Hebei Agricultural University, Baoding 071001, China
4
Beijing Institute of Pharmacology & Toxicology, Beijing 100850, China
5
Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 24 May 2018 / Revised: 21 June 2018 / Accepted: 28 June 2018 / Published: 2 July 2018
(This article belongs to the Special Issue Recent Advances in the Development of Antiviral Agents)
Full-Text   |   PDF [616 KB, uploaded 2 July 2018]   |  

Abstract

Reverse transcriptase inhibitors (RTIs), including nucleoside RTIs (NRTIs) and non-nucleoside RTIs (NNRTIs), are critical antiretroviral drugs for the treatment of human immunodeficiency virus (HIV) infection. Emergence of multi-RTI resistance calls for the development of more potent therapeutics or regimens against RTI-resistant strains. Here, we demonstrated that combining azidothymidine (AZT) with a new NNRTIs under development, diarylpyridine (DAPA)-2e, diarylanilin (DAAN)-14h, or DAAN-15h, resulted in strong synergism against infection by divergent HIV-1 strains, including those resistant to NRTIs and NNRTIs, suggesting the potential for developing these novel NNRTIs as salvage therapy for HIV/acquired immune deficiency syndrome (AIDS) patients. View Full-Text
Keywords: HIV-1; HAART; NNRTIs; antiviral activity; combination; synergism HIV-1; HAART; NNRTIs; antiviral activity; combination; synergism
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Yu, F.; Li, W.; Wang, L.; Dai, Y.; Lu, X.; Wang, Q.; Xie, L.; Jiang, S. Combining New Non-Nucleoside Reverse Transcriptase Inhibitors (RTIs) with AZT Results in Strong Synergism against Multi-RTI-Resistant HIV-1 Strains. Molecules 2018, 23, 1599.

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