TY  - JOUR
A1  - Sarukhanyan, Edita
A1  - Shanmugam, Tipack Ayothyapattanam
A1  - Dandekar, Thomas
T1  - In silico studies reveal Peramivir and Zanamivir as an optimal drug treatment even if H7N9 avian type influenza virus acquires further resistance
JF  - Molecules
N2  - An epidemic of avian type H7N9 influenza virus, which took place in China in 2013, was enhanced by a naturally occurring R294K mutation resistant against Oseltamivir at the catalytic site of the neuraminidase. To cope with such drug-resistant neuraminidase mutations, we applied the molecular docking technique to evaluate the fitness of the available drugs such as Oseltamivir, Zanamivir, Peramivir, Laninamivir, L-Arginine and Benserazide hydrochloride concerning the N9 enzyme with single (R294K, R119K, R372K), double (R119_294K, R119_372K, R294_372K) and triple (R119_294_372K) mutations in the pocket. We found that the drugs Peramivir and Zanamivir score best amongst the studied compounds, demonstrating their high binding potential towards the pockets with the considered mutations. Despite the fact that mutations changed the shape of the pocket and reduced the binding strength for all drugs, Peramivir was the only drug that formed interactions with the key residues at positions 119, 294 and 372 in the pocket of the triple N9 mutant, while Zanamivir demonstrated the lowest RMSD value (0.7 Å) with respect to the reference structure.
KW  - H7N9 influenza virus
KW  - neuraminidase
KW  - mutation
KW  - binding pocket
KW  - molecular docking
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-288240
SN  - 1420-3049
VL  - 27
IS  - 18
ER  -