Structural Biology of HIV Integrase Strand Transfer Inhibitors

Trends Pharmacol Sci. 2020 Sep;41(9):611-626. doi: 10.1016/ Epub 2020 Jul 3.


Integrase (IN) strand transfer inhibitors (INSTIs) are recent compounds in the antiretroviral arsenal used against HIV. INSTIs work by blocking retroviral integration; an essential step in the viral lifecycle that is catalyzed by the virally encoded IN protein within a nucleoprotein assembly called an intasome. Recent structures of lentiviral intasomes from simian immunodeficiency virus (SIV) and HIV have clarified the INSTI binding modes within the intasome active sites and helped elucidate an important mechanism of viral resistance. The structures provide an accurate depiction of interactions of intasomes and INSTIs to be leveraged for structure-based drug design. Here, we review these recent structural findings and contrast with earlier studies on prototype foamy virus intasomes. We also present and discuss examples of the latest chemical compounds that show promising inhibitory potential as INSTI candidates.

Keywords: HIV; antiretroviral therapy; drug resistance; integrase; structure-based drug design.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biology
  • Catalytic Domain
  • HIV Integrase Inhibitors* / pharmacology
  • HIV Integrase* / metabolism
  • HIV-1* / metabolism
  • Humans


  • HIV Integrase Inhibitors
  • HIV Integrase