Reverse transcriptase inhibitors are antiviral drugs that block reverse transcriptase, the enzyme retroviruses and certain other viruses use to copy their RNA genome into DNA for integration into the host cell. By halting this step, the inhibitors prevent the virus from completing its replication cycle, and they for…
Reverse transcriptase inhibitors are antiviral drugs that block reverse transcriptase, the enzyme retroviruses and certain other viruses use to copy their RNA genome into DNA for integration into the host cell. By halting this step, the inhibitors prevent the virus from completing its replication cycle, and they form the backbone of antiretroviral therapy for HIV and are also used against hepatitis B. Two main mechanistic classes exist. Nucleoside and nucleotide reverse transcriptase inhibitors are analogues of natural DNA building blocks; once incorporated into the growing viral DNA chain they cause premature termination because they lack the chemical group needed to extend the strand. Non-nucleoside reverse transcriptase inhibitors instead bind a distinct allosteric pocket on the enzyme, changing its shape and impairing its catalytic activity. The two classes are often combined within multidrug regimens to suppress viral load and reduce the emergence of resistance. Resistance arises when mutations in the reverse transcriptase gene reduce drug binding, and surveillance of drug-resistance patterns guides regimen selection, particularly in treatment-experienced patients. Like other antiretrovirals, these agents require attention to adverse effects; because nucleoside analogues can affect host enzymes such as telomerase and mitochondrial polymerases, toxicities including metabolic disturbances and accelerated cellular aging are recognized considerations in long-term use.
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