Sialic acid (N-acetylneuraminic acid) (Sia)

Sialic acids are a family of nine-carbon acidic monosaccharides typically located at the terminal positions of cell surface glycoconjugates [1]. In humans, the most prevalent form is N-acetylneuraminic acid (Neu5Ac), which plays a critical role in mediating cell-cell interactions and stabilizing protein conformations [2]. These molecules serve as essential receptors for various pathogens; for instance, influenza viruses utilize their hemagglutinin protein to bind to host sialic acids to initiate infection [4]. Furthermore, sialic acids are key regulators of the immune system, interacting with Siglecs (sialic acid-binding immunoglobulin-type lectins) to modulate immune cell activation and prevent autoimmunity [1][3]. In oncology, hypersialylation of tumor cells is a well-documented mechanism for immune evasion and increased metastatic potential, as it can mask antigenic epitopes and inhibit natural killer cell activity [3]. Therapeutic interventions include neuraminidase inhibitors like oseltamivir, which prevent the release of viral progeny by blocking the cleavage of host sialic acids, and experimental sialidases like DAS181 that enzymatically remove these receptors from the respiratory epithelium [4].

Other names

N-acetylneuraminic acidNeu5AcNeuraminic acidSialic acidsSialyl groups

Drugs targeting host sialic acid interactions primarily function by inhibiting viral neuraminidase enzymes, which prevents the cleavage of sialic acid residues and traps newly formed virions on the host cell surface [4]. Alternatively, host-directed therapies like DAS181 act as sialidases to enzymatically remove terminal sialic acids from the host cell surface, thereby eliminating the attachment points for respiratory viruses [4]. In cancer, sialyltransferase inhibitors are being explored to reduce hypersialylation and restore immune recognition [3].