Mechanisms of inhibition and resistance to antiviral drugs targeting human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV)

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Although human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV) are very different viruses, the replication of their genome involves a reverse transcription process catalyzed by the viral reverse transcriptase (RT). Nucleoside reverse transcriptase inhibitors (NRTIs) are widely used for the treatment of HIV-1 and HBV infections. Unfortunately, the viruses manage to escape treatment by developing resistance. The main focus of this research is EFdA, a deoxyadenosine analog which blocks HIV-1 replication with remarkable potency. The inhibition stems mainly from the inability of the EFdA-terminated primer to translocate which is a novel mechanism therefore we termed EFdA as a translocation defective RT inhibitor (TDRTI). EFdA is shown here to be very effective not only against wild-type viruses but also against viruses that are resistant to widely used antiretrovirals.