Sialic acid-containing glycoconjugates (SIA)

Sialic acid-containing glycoconjugates are terminal sugar residues, primarily N-acetylneuraminic acid (Neu5Ac), found on glycoproteins and glycolipids of the host cell surface glycocalyx [1]. These molecules serve as the primary receptors for the attachment of various viruses, including influenza and parainfluenza, via the viral hemagglutinin protein [2]. During the final stages of the viral life cycle, the viral enzyme neuraminidase cleaves these sialic acid residues to prevent the aggregation of progeny virions and facilitate their release from the host cell [3]. Because these substrates are essential for both viral entry and egress, they represent a strategic target for host-directed antiviral therapy. DAS181 (Fludase) is an investigational recombinant sialidase that targets these host substrates by enzymatically removing them from the respiratory epithelium, thereby providing a broad-spectrum barrier against infection [4]. This approach is designed to minimize the development of drug resistance, which is a common challenge with direct-acting antivirals that target viral proteins [5]. Sources: [1] Varki A. Sialic acids in human health and disease. Trends Mol Med. 2008. [2] Skehel JJ, Wiley DC. Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem. 2000. [3] von Itzstein M. The war against influenza: neuraminidase inhibitors. Nat Rev Drug Discov. 2007. [4] Moss RB, et al. DAS181 for treatment of parainfluenza virus infection in immunocompromised patients. J Infect Dis. 2011. [5] Triana-Baltzer GB, et al. DAS181, a sialidase fusion protein, protects mice from lethal avian influenza H5N1 virus infection. J Infect Dis. 2009.

Other names

Sialic acid receptorsN-acetylneuraminic acid (Neu5Ac) receptorsSialosidesHost cell surface sialic acidsTerminal sialic acid residues

Enzymatic removal of terminal sialic acid residues from host cell surface glycoconjugates to inhibit viral entry and release.