SARS-CoV 2; Possible alternative virus receptors and pathophysiological determinants

Abstract

Understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highjacks epithelial cells and infiltrates the lung, as well as other organs and tissues, is essential for developing treatment strategies and vaccines against this highly contagious virus. Another major goal is to fully elucidate the mechanisms by which SARS-CoV- 2 bypasses the innate immune system and induces a cytokine storm, and its effects on mortality. Currently, SARS- CoV-2 is thought to evade innate antiviral immunity, undergo endocytosis, and fuse with the host cell membrane by exploiting ACE2 receptors and the protease TMMPRSS2, with cathepsin B/L as alternative protease, for entry into the epithelial cells of tissues vulnerable to developing coronavirus disease 2019 (COVID-19) symptoms. However, the incorporation of new and unique binding sites, i.e., O-linked glycans, and the preservation and augmentation of effective binding sites (N-linked glycans) on the outer membrane of SARS-CoV-2 may represent other strategies of infecting the human host. Here, I will rationalize the possibility that other host molecules-i.e., sugar molecules and the sialic acidsN-glycolylneuraminic acid, N-acetylneuraminic acid, and their derivates could be viable candidates for the use as virus receptors by SARS-CoV-2 and/or serve as determinants for the adherence on ACE2 of SARS-CoV-2.

Keywords: Antibodies; COVID-19; Glycan shield; Neu5Ac; Neu5Gc; Pandemic; SARS-COV-2; Sialic acids; Vaccine.

Fig. 1

A schematic overview of the spike glycoprotein S and its subunits S1 and S2. Note the Olinked glycans on S1 in the vicinity of the TMMPRSS2 cleavage site (dashed line). TMMPRSS2 cleaves S2 from S1, facilitating the connection between S1 and hACE2. N-linked glycans (continuous line) cover both the S1 and S2 subunit as part of the masking glycan shield. Different sialic acids serve as part of the glycan shield and could be determinants for viral entry into epithelial cells. The innate antiviral immune system is evaded. and tricked through the possible use of Neu5Gc, Neu5Ac, and their derivates (given as sialic acids) by SARSCoV-2.