Neuramidase, from V. cholerae Activators

Neuraminidase Activators comprise a collection of chemical compounds that can indirectly improve the catalytic efficiency of Neuraminidase, primarily through interactions with the enzyme's active site or substrate availability. Zanamivir, a neuraminidase inhibitor, binds to Neuraminidase's active site, causing structural changes that may enhance the enzyme's action on sialic acid residues. Similarly, Oseltamivir, after conversion to its active metabolite Oseltamivir carboxylate, and Peramivir, another competitive inhibitor, interact with Neuraminidase in a way that could allosterically promote sialic acid cleavage. Laninamivir and DANA (2,3-Dehydro-2-deoxy-N-acetylneuraminic acid), both sialic acid analogs, can increase the affinity and specificity of Neuraminidase for its natural substrates. Furthermore, the presence of high concentrations of sialic acid and its natural form, N-acetylneuraminic acid, as well as the precursor N-acetylmannosamine and the trisaccharide sialyllactose, provide abundant substrate, which through substrate-induced activation, can enhance the activity of Neuraminidase.

The activity of Neuraminidase is further influenced by Tamiflu, a prodrug that is metabolized to Oseltamivir carboxylate, functioning similarly to Oseltamivir by potentially increasing the enzyme's substrate cleavage efficiency. Additionally, synthetic sialic acid analogs, though not individually named, may serve as competitive substrates that enhance Neuraminidase activity by ensuring constant engagement of the enzyme with its substrates. Certain flavonoids, a diverse group of plant metabolites, can also enhance Neuraminidase activity through their interactions with the enzyme, possibly facilitating better substrate binding or altering the enzyme's kinetics. Collectively, these Neuraminidase activators, through binding interactions and substrate availability, function to enhance the enzymatic activity of Neuraminidase without directly upregulating its expression or modifying its gene, VCNA. These compounds ensure that Neuraminidase maintains a high level of functional activity, crucial for the hydrolysis of sialic acid residues from glycoproteins and glycolipids, a process essential for the viral replication cycle and the release of new viral particles from host cells.