Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine.

ABSTRACT: Chronic hepatitis B virus (HBV) infection is a major public health problem that affects millions of people worldwide. Nucleoside analogue reverse transcriptase (RT) inhibitors, such as entecavir (ETV) and lamivudine (3TC), serve as crucial anti-HBV drugs. However, structural studies of HBV RT have been hampered due to its unexpectedly poor solubility. Here, we show that human immunodeficiency virus type-1 (HIV-1) with HBV-associated amino acid substitutions Y115F/F116Y/Q151M in its RT (HIV^{Y115F/F116Y/Q151M}) is highly susceptible to ETV and 3TC. Additionally, we experimentally simulated previously reported ETV/3TC resistance for HBV using HIV^{Y115F/F116Y/Q151M} with F160M/M184V (L180M/M204V in HBV RT) substituted. We determined crystal structures for HIV-1 RT^Y115F/F

SUBMITTER: Yasutake Y 

PROVIDER: S-EPMC7033138 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature