Discovery of Ten Anti-HIV Hit Compounds and Preliminary Pharmacological Mechanisms Studies


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Background:The research and development of HIV drugs is very important, but at the same time it is a long cycle and expensive system project. High-throughput drug screening systems and molecular libraries of potential hit compounds remain the main ways for the discovery of hit compounds with anti-HIV activity.

Objective:The aim of this study was to screen out the hit compounds against HIV-1 in the natural product molecule library and the antiviral molecule library, and elucidate the molecular mechanism of their inhibition of HIV-1, so as to provide a new choice for AIDS drug research.

Methods:In this study, a drug screening system using HIV Rev-dependent indicator cell line (Rev-A3R5-GFP reporter cells) with pseudoviruses (pNL4-3) was used. The natural drug molecule library and antiviral molecule library were screened, and preliminary drug mechanism studies were performed.

Results:Ten promising hit compounds were screened. These ten molecules and their drug inhibitory IC50 were as follows: Cephaeline (0.50 µM), Yadanziolide A (8.82 µM), Bruceine D (2.48 µM), Astragaloside IV (4.30 µM), RX-3117 (1.32 µM), Harringtonine (0.63 µM), Tubercidin (0.41 µM), Theaflavine-3, 3'-digallate (0.41 µM), Ginkgetin (10.76 µM), ZK756326 (5.97 µM). The results of the Time of additions showed that except for Astragaloside IV and Theaflavine-3, 3'-digallate had a weak entry inhibition effect, and it was speculated that all ten compounds had an intracellular inhibition effect. Cephaeline, Harringtonine, Astragaloside IV, Bruceine D, and Tubercidin may have pre-reverse transcriptional inhibition. Yadanziolide A, Theaflavine-3, 3'-digallate, Ginkgetin and RX-3117 may be in the post-reverse transcriptional inhibition. The inhibitory effect of ZK 75632 may be in the reverse transcriptional process.

Conclusion:A drug screening system using Rev-A3R5-GFP reporter cells with pseudoviruses (pNL4-3) is highly efficient. This study provided potential hit compounds for new HIV drug research.

作者简介

Yushan Lian

School of Public Health, Southern Medical University

Email: info@benthamscience.net

Zhimin Huang

School of Public Health, Guangdong Medical University

Email: info@benthamscience.net

Xinyi Liu

The State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Biology, Tsinghua Shenzhen International Graduate School,, Tsinghua University

Email: info@benthamscience.net

Zhicheng Deng

The State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Biology, Tsinghua Shenzhen International Graduate School, Tsinghua University

Email: info@benthamscience.net

Dan Gao

The State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Biology, Tsinghua Shenzhen International Graduate School,, Tsinghua University

编辑信件的主要联系方式.
Email: info@benthamscience.net

Xiaohui Wang

Department of Prevention and control of infectious diseases, School of Public Health, Southern Medical University

编辑信件的主要联系方式.
Email: info@benthamscience.net

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