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Review
. 2014 Oct:8:1-9.
doi: 10.1016/j.coviro.2014.04.005. Epub 2014 May 9.

Nucleoside/nucleotide analog inhibitors of hepatitis B virus polymerase: mechanism of action and resistance

Affiliations
Review

Nucleoside/nucleotide analog inhibitors of hepatitis B virus polymerase: mechanism of action and resistance

Luis Menéndez-Arias et al. Curr Opin Virol. 2014 Oct.

Abstract

Hepatitis B virus (HBV) polymerase and human immunodeficiency virus (HIV) reverse transcriptase are structurally related. However, the HBV enzyme has a protein priming activity absent in the HIV enzyme. Approved nucleoside/nucleotide inhibitors of the HBV polymerase include lamivudine, adefovir, telbivudine, entecavir and tenofovir. Although most of them target DNA elongation, guanosine and adenosine analogs (e.g. entecavir and tenofovir, respectively) also impair protein priming. Major mutational patterns conferring nucleoside/nucleotide analog resistance include the combinations rtL180M/rtM204(I/V) (for lamivudine, entecavir, telbivudine and clevudine) and rtA181V/rtN236T (for adefovir and tenofovir). However, development of drug resistance is very slow for entecavir and tenofovir. Novel nucleoside/nucleotide analogs in advanced clinical trials include phosphonates similar to adefovir or tenofovir, and new tenofovir derivatives with improved pharmacological properties.

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