Amantadine was used for chemoprophylaxis of influenza A but resistance emerges within days of monotherapy. The drug acts on which viral target, and what change mediates resistance?

• A Neuraminidase; substitution at position 275 (H275Y)
• B PB1 polymerase subunit; cap-snatching defects
• C Hemagglutinin; glycosylation changes around the receptor-binding site
• D M2 ion channel; mutation of the transmembrane domain of the M2 protein ✓

Explanation

Amantadine and rimantadine block the M2 proton ion channel of influenza A, preventing acid-mediated uncoating of the virion inside endosomes. Single amino-acid substitutions in the transmembrane pore of the M2 protein abolish susceptibility, and resistant virus is transmissible, so circulating strains are now largely resistant. The H275Y mutation confers oseltamivir resistance on N1 neuraminidase, which kills the most tempting distractor linking resistance to the wrong drug class.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.