Inhaled Zanamivir as a Candidate for SARS-CoV-2 Antiviral Drug

Zanamivir inhibits the neuraminidase of influenza A and B viruses, both capable of infecting human, avian and other mammalian hosts. By inhibiting neuraminidase, it prevents the detachment of replicated virions, which are formed in influenza-infected respiratory-epithelial cells. Creative Biolabs has established excellent platforms for drug development. We provide a variety of antiviral agent development services to meet the diverse needs of our customers.

Antiviral Drug: Inhaled Zanamivir

The framework of zanamivir is the transition state analog of neuraminidase, Neu5Ac2en, and zanamivir is the 4-guanadino-derivative of that compound. Zanamivir inhibits the viral enzyme neuraminidase. The dissociation constant varies over approximately one order of magnitude, depending on the antigenic subtype of the neuraminidase. Although the amino acid residues that form the catalytic pocket are mostly preserved in all virus strains, small changes to the underlying atomic substructure apparently give rise to this activity spectrum that, for zanamivir and related Neu5Ac2en derivatives, manifests itself as marginally tighter binding to type A than type B neuraminidases.

The oral bioavailability of a 500 mg dose of zanamivir is very low and in the range of 1 to 5%, which precludes this route of drug administration. Oral inhalation of dry powdered zanamivir gives an approximately 50% higher bioavailability than intranasal drops or spray and achieves high local concentrations of drug in the upper airways, with 78% of a 10-mg dose residing in the oropharynx and 13% in the bronchi and lungs. Therefore, the dose of zanamivir is 10 mg inhaled twice daily, delivering high levels to the upper respiratory tract, estimated to be up to 10,000 nM.

Fig.1 The relationship between zanamivir and some of the amino acids in the neuraminidase active site.

Services

Zanamivir is one of the early examples of structure-based drug design (SBDD) in the sense that the protein structure directed the design of the ligand and the protein-bound ligand conformation is close to the designed structure. The SBDD methods are the inventive processes of finding new drugs based on the knowledge of the biological target. Based on the progress of the SBDD, Creative Biolabs has designed a collection of antiviral drugs against SARS-CoV-2. We can provide the SBDD methods for the development of new inhibitors used for SARS-CoV-2 treatment.

Creative Biolabs has long-term devoted to the development of antiviral agents. With years of experience, our scientists have established professional platforms to boost our global customers’ research and project goals. We can provide you with outstanding support and meet your specific needs. If you are interested in our services, please contact us for more details.

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