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

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.

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.

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.

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.

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.