TY - JOUR
T1 - Inhibition of viral group-1 and group-2 neuraminidases by oseltamivir
T2 - A comparative structural analysis by the ScrewFit algorithm
AU - Calligari, Paolo A.
AU - Kneller, Gerald R.
AU - Giansanti, Andrea
AU - Ascenzi, Paolo
AU - Porrello, Alessandro
AU - Bocedi, Alessio
PY - 2009/4
Y1 - 2009/4
N2 - The viral surface glycoprotein neuraminidase (NA) allows the influenza virus penetration and the egress of virions. NAs are classified as A, B, and C. Type-A NAs from influenza virus are subdivided into two phylogenetically distinct families, group-1 and group-2. NA inhibition by oseltamivir represents a therapeutic approach against the avian influenza virus H5N1. Here, structural bases for oseltamivir recognition by group-1 NA1, NA8 and group-2 NA9 are highlighted by the ScrewFit algorithm for quantitative structure comparison. Oseltamivir binding to NA1 and NA8 affects the geometry of Glu119 and of regions Arg130-Ser160, Val240-Gly260, and Asp330-Glu382, leading to multiple NA conformations. Additionally, although NA1 and NA9 share almost the same oseltamivir-bound final conformation, they show some relevant differences as suggested by the ScrewFit algorithm. These results indicate that the design of new NA inhibitors should take into account these family-specific effects induced on the whole structure of NAs.
AB - The viral surface glycoprotein neuraminidase (NA) allows the influenza virus penetration and the egress of virions. NAs are classified as A, B, and C. Type-A NAs from influenza virus are subdivided into two phylogenetically distinct families, group-1 and group-2. NA inhibition by oseltamivir represents a therapeutic approach against the avian influenza virus H5N1. Here, structural bases for oseltamivir recognition by group-1 NA1, NA8 and group-2 NA9 are highlighted by the ScrewFit algorithm for quantitative structure comparison. Oseltamivir binding to NA1 and NA8 affects the geometry of Glu119 and of regions Arg130-Ser160, Val240-Gly260, and Asp330-Glu382, leading to multiple NA conformations. Additionally, although NA1 and NA9 share almost the same oseltamivir-bound final conformation, they show some relevant differences as suggested by the ScrewFit algorithm. These results indicate that the design of new NA inhibitors should take into account these family-specific effects induced on the whole structure of NAs.
KW - Comparative structural analysis
KW - Enzyme structure
KW - Neuraminidase
KW - Oseltamivir binding
KW - ScrewFit algorithm
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U2 - 10.1016/j.bpc.2009.01.004
DO - 10.1016/j.bpc.2009.01.004
M3 - Article
C2 - 19195766
AN - SCOPUS:60249087300
VL - 141
SP - 117
EP - 123
JO - Biophysical Chemistry
JF - Biophysical Chemistry
SN - 0301-4622
IS - 1
ER -