Mechanism of Resistance to Oseltamivir

The neuraminidase active site changes shape to create a pocket for oseltamivir, whereas it accommodates zanamivir without such a change. Any of several mutations may prevent the binding of oseltamivir by preventing the formation of this pocket; the oseltamivir-resistant virus can nonetheless bind to the host-cell sialic acid receptor and to zanamivir. The pocket for oseltamivir is created by the rotation of E276 and bonding of the amino acid to R224 — events that are prevented by the mutations R292K, N294S, and H274Y and therefore result in resistance to oseltamivir. An E119V mutation may permit the binding of a water molecule in the space created by the smaller valine, also interfering with oseltamivir binding. None of these mutations prevent the binding of zanamivir or of the natural sialic acid substrate.

Category:

Science & Technology

Tags:

• Influenza A Virus
• Oseltamivir
• Drug Resistance