Screening and Characterization of Anti-HIV Small Molecule Inhibitors




Deng, Jiaoying

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The human immunodeficiency virus (HIV) afflicts over 30 million people worldwide. The current anti-retroviral therapy has been proved effective and improved the life expectancy of HIV infected individuals. However, it still has numerous limitations, including side effects, drug interactions, poor drug absorption and viral drug resistance. Discovery and development of novel anti-HIV drugs that overcome current limitations is in great demand and still one of the major interests and focuses in the field of HIV therapy. Great efforts have been put on identifying effective anti-HIV drugs and studying the action mechanisms of the drugs on HIV in this research work. Up to forty compounds from different research institutes have been screened using a HIV Rev-dependent indicator T cell line, Rev-CEM-GFP-Luc. Eight drugs that inhibited HIV infection at non-toxic dosages have been identified through the screening. Further mechanism study has then been performed on the identified drugs and two of them (NSC377384 and NSC44556) are selected and studied in details. The study has revealed that these two selected drugs have totally different mechanisms of action on HIV. NSC377384 targets the late steps of HIV life cycle, and inhibits HIV replication most likely by inhibiting viral assembly and budding, causing a decrease in viral particle release. NSC44556, in contrast, targets the early steps of HIV life cycle, and likely specifically inhibits the function of HIV reverse transcriptase, leading to a decrease in viral DNA synthesis. The discoveries in this research work will provide useful help to the development of better anti-HIV drugs overcoming some current limitations. It is also expected that this research work can contribute to the future research in better meeting the societal demand on novel anti-HIV drugs.



Anti-HIV, HIV life cycle, Inhibitors, Mechanism, Drug screening