Targeting Integrase Enzyme: A Therapeutic Approach to Combat HIV Resistance

Global Human Immunodeficiency Virus (HIV) statistics by the World Health Organization (WHO) for the year 2017 was estimated to be 36.9 (31.1-43.9) million. Antiviral drug resistance poses a serious threat to public health and requires immediate action. Retroviral Integrase (IN), a component enzyme in the retroviral pre-integration complex (PIC) enables a retrovirus to incorporate its genetic material into the host DNA. Development of resistance by the current integrases invites immediate attention of the drug discovery community for the development of new second-generation Integrase Strand Transfer Inhibitors (INSTIs). It will exhibit greater efficacy against Elvitegravir (EVG) and Raltegravir (RAL) resistant strains of HIV. This review focuses on the mechanism, importance of integrase structure, function and current research on small molecule inhibitors of integrase to overcome drug resistance. The molecular mechanism of retroviral integrase inhibition and the evolution of resistance are also explored.