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

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

Volume: 22

Author(s): Yushan Lian, Zhimin Huang, Xinyi Liu, Zhicheng Deng, Dan Gao*Xiaohui Wang*

Affiliation:

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

• Department of Prevention and control of infectious diseases, School of public health, Southern Medical University, Guangzhou, Guangdong, China
• Department of HIV/AIDS Prevention and Control, Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China

Keywords: HIV, Drug screening, Precursor compounds, Harringtonine, Bruceine D, Natural product molecular libraries, Antiviral molecular libraries

Abstract: 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.

Cite this article as:

Lian Yushan, Huang Zhimin, Liu Xinyi, Deng Zhicheng, Gao Dan*, Wang Xiaohui*, Discovery of Ten Anti-HIV Hit Compounds and Preliminary Pharmacological Mechanisms Studies, Current HIV Research 2024; 22 () . https://dx.doi.org/10.2174/011570162X301289240320082840