HIV integrase strand transfer inhibitors (INSTIs) — raltegravir, elvitegravir, dolutegravir, bictegravir — prevent viral DNA integration into the host genome. Which step specifically does this drug class inhibit?
- A 3'-processing: endonucleolytic cleavage of 3' dinucleotides from viral DNA ends
- B Nuclear import of the preintegration complex
- C Strand transfer: covalent insertion of processed viral DNA into host chromosomal DNA ✓
- D Disassembly of the HIV capsid core (uncoating)
Explanation
HIV integrase inhibitors (INSTIs) target the strand transfer step of the integration process. HIV integrase performs two sequential reactions: (1) 3'-processing — cleavage of two nucleotides from the 3' ends of viral DNA in the cytoplasm, creating reactive hydroxyl groups; and (2) strand transfer — transesterification inserts the processed viral DNA into the host chromosome. INSTIs chelate the divalent metal ions (Mg2+) in the active site of integrase, specifically blocking the strand transfer reaction. They do not inhibit 3'-processing. Dolutegravir and bictegravir have a high genetic barrier to resistance and are preferred in first-line ART regimens.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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