Inhibition of the HIV Protein VIF by Small Molecules

Mentors: Shailesh Metkar, Frank An

Millions of people worldwide are infected with Human Immunodeficiency Virus (HIV). HIV reproduces by incorporating its own genome into the host human cells’ DNA. The enzyme APOBEC3G (A3G) acts in cells to prevent the viral genome from being incorporated into the host’s DNA. However, the HIV protein Viral Infectivity Factor (VIF) inhibits A3G. In order for VIF to inhibit A3G, VIF proteins must bind to each other and multimerize. Thus Eamon sought to discover which small molecules would prevent the multimerization of VIF, and therefore potentially inihibit reproduction of HIV.

Eamon re-tested 395 candidate compounds from a previous experiment, for their abilities to inhibit VIF multimerization at varying doses. Then he tested the candidate compounds to see if they were toxic to cells, using the Cell-Titer Glo assay. Eamon found that 77 of the candidate molecules were active inhibitors of VIF, and of those 77, ten were non-toxic. These molecules have potential for further testing as inhibitors of reproduction of the HIV virus.



Eamon, a senior at Boston Latin School, researched chemical compounds that inhibit the function of an HIV protein named "Viral Infectivity Factor."