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HIV reverse transcriptase is a heterodimeric enzyme (p66/p51 subunits) whose polymerase activity copies the viral RNA genome into double-stranded DNA, which is integrated into the host genome by the viral integrase. Its RNase H activity degrades the RNA strand of RNA:DNA hybrids after DNA synthesis, essential for viral replication. HIV reverse transcriptase is unique to retroviruses, and drugs targeting it include NRTIs and NNRTIs, forming the backbone of antiretroviral therapy. Hepatitis B polymerase is a multifunctional viral enzyme that synthesizes HBV DNA from its pregenomic RNA template. Like HIV RT, it possesses reverse transcriptase and RNase H activities and is essential for HBV replication and maintenance of viral genome in host hepatocytes. Therapies for hepatitis B often target this polymerase using nucleoside/nucleotide analogues.
Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs): mimic normal nucleotides, incorporate into viral DNA, and cause chain termination. Non-nucleoside reverse transcriptase inhibitors (NNRTIs): bind allosteric site, induce conformational change, inhibit enzyme function. For HBV polymerase: nucleotide/nucleoside analogs compete with natural substrates, causing premature chain termination.
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