4'-modified nucleoside analogs: potent inhibitors active against entecavir-resistant hepatitis B virus.

ABSTRACT:

Unlabelled

Certain nucleoside/nucleotide reverse transcriptase (RT) inhibitors (NRTIs) are effective against human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV). However, both viruses often acquire NRTI resistance, making it crucial to develop more-potent agents that offer profound viral suppression. Here, we report that 4'-C-cyano-2-amino-2'-deoxyadenosine (CAdA) is a novel, highly potent inhibitor of both HBV (half maximal inhibitory concentration [IC50 ] = 0.4 nM) and HIV-1 (IC50  = 0.4 nM). In contrast, the approved anti-HBV NRTI, entecavir (ETV), potently inhibits HBV (IC50  = 0.7 nM), but is much less active against HIV-1 (IC50  = 1,000 nM). Similarly, the highly potent HIV-1 inhibitor, 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA; IC50  = 0.3 nM) is less a

SUBMITTER: Takamatsu Y 

PROVIDER: S-EPMC4589464 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature