Search for Ligands Complementary to the 430-cavity of Influenza Virus Neuraminidase by Virtual Screening

Dmitry K. Nilov; Michaela Schmidtke; Vadim A. Makarov; Vytas K. Švedas

doi:10.14529/jsfi220207

Authors

Dmitry K. Nilov Lomonosov Moscow State University, Moscow, Russia
Michaela Schmidtke Department of Virology and Antiviral Therapy, Jena University Hospital, Jena, Germany
Vadim A. Makarov Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russia
Vytas K. Švedas Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, Moscow, Russia

DOI:

https://doi.org/10.14529/jsfi220207

Keywords:

influenza, neuraminidase, 430-cavity, inhibitor, anthrapyrazole

Abstract

An anthrapyrazole derivative STK663786 has been identified as a selective ligand of the socalled 430-cavity of influenza virus neuraminidase at virtual screening of a library of low-molecularweight compounds. It is able to form favorable contacts with hydrophobic residues as well as cationπ interaction and hydrogen bonds with the polar Arg371 residue. The experimentally determined EC₅₀ values have been found to be 19 and 30 µM for viruses H1N1 and H3N2, respectively. Complementarity of STK663786 to the 430-cavity adjacent to the sialic acid binding subsite in the active center of neuraminidase makes this compound a valuable structural fragment at construction of bifunctional inhibitors of the enzyme.

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