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  • Mechanism-based covalent neuraminidase inhibitors with broad-spectrum influenza antiviral activity.

Mechanism-based covalent neuraminidase inhibitors with broad-spectrum influenza antiviral activity.

Science (New York, N.Y.) (2013-02-23)
Jin-Hyo Kim, Ricardo Resende, Tom Wennekes, Hong-Ming Chen, Nicole Bance, Sabrina Buchini, Andrew G Watts, Pat Pilling, Victor A Streltsov, Martin Petric, Richard Liggins, Susan Barrett, Jennifer L McKimm-Breschkin, Masahiro Niikura, Stephen G Withers
ABSTRACT

Influenza antiviral agents play important roles in modulating disease severity and in controlling pandemics while vaccines are prepared, but the development of resistance to agents like the commonly used neuraminidase inhibitor oseltamivir may limit their future utility. We report here on a new class of specific, mechanism-based anti-influenza drugs that function through the formation of a stabilized covalent intermediate in the influenza neuraminidase enzyme, and we confirm this mode of action with structural and mechanistic studies. These compounds function in cell-based assays and in animal models, with efficacies comparable to that of the neuraminidase inhibitor zanamivir and with broad-spectrum activity against drug-resistant strains in vitro. The similarity of their structure to that of the natural substrate and their mechanism-based design make these attractive antiviral candidates.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Neuraminidase Agarose from Clostridium perfringens (C. welchii), Type VI-A, ammonium sulfate suspension
Sigma-Aldrich
α(2→3) Neuraminidase from Streptococcus pneumoniae, buffered aqueous solution
Sigma-Aldrich
Neuraminidase from Clostridium perfringens (C. welchii), Suitable for manufacturing of diagnostic kits and reagents, Type V, lyophilized powder
Sigma-Aldrich
Neuraminidase from Clostridium perfringens (C. welchii), Type VIII, lyophilized powder, 10-20 units/mg protein (using 4MU-NANA), 3.5-8.0 units/mg protein (mucin)
Sigma-Aldrich
α(2→3,6) Neuraminidase from Clostridium perfringens (C. welchii), recombinant, expressed in E. coli, buffered aqueous solution, ≥250 units/mg protein
Sigma-Aldrich
Neuraminidase from Clostridium perfringens (C. welchii), Type VI, lyophilized powder, 6-15 units/mg protein (using 4MU-NANA), 2-10 units/mg protein (mucin)
Sigma-Aldrich
Neuraminidase from Clostridium perfringens (C. welchii), Type X, lyophilized powder, ≥50 units/mg protein (using 4MU-NANA)
Sigma-Aldrich
α(2→3,6,8,9) Neuraminidase from Arthrobacter ureafaciens, Proteomics Grade, suitable for MALDI-TOF MS
Sigma-Aldrich
Neuraminidase from Vibrio cholerae, Type II, buffered aqueous solution, 8-24 units/mg protein (Lowry, using NAN-lactose)
Sigma-Aldrich
Neuraminidase from Vibrio cholerae, ≥1.5 U/mL, specific activity ≥ 1.5U/mg protein
Sigma-Aldrich
Neuraminidase from Vibrio cholerae, Type III, buffered aqueous solution, 0.2 μm filtered, 1-5 units/mg protein (Lowry, using NAN-lactose)
Sigma-Aldrich
α(2→3,6,8,9) Neuraminidase from Arthrobacter ureafaciens, recombinant, expressed in E. coli, buffered aqueous solution
Sigma-Aldrich
Zanamivir, ≥98% (HPLC)