Involvement of sialoglycans in SARS‐COV‐2 infection: Opportunities and challenges for glyco‐based inhibitors

Abstract

Viral infections have been the causes of global pandemics, including the ongoing coronavirus disease 2019, which prompted the investigation into the infection mechanisms to find treatment and aid the vaccine design. Betacoronaviruses use spike glycoprotein on their surface to bind to host receptors, aiding their host attachment and cell fusion. Protein-glycan interaction has been implicated in the viral entry mechanism of many viruses and has recently been shown in SARS-CoV-2. Here, we reviewed the current knowledge on protein-glycan interactions that facilitate SARS-CoV-2 host entry, with special interest in sialoglycans present on both the virions and host cell surfaces. We also analyze how such information provides opportunities and challenges in glyco-based inhibitors.

The Effect of Select SARS-CoV-2 N-Linked Glycan and Variant of Concern Spike Protein Mutations on C-Type Lectin-Receptor-Mediated Infection

“…Thus, it is conceivable that mutations in the Omicron BA.2 strain could allow conformational changes that allow the spike protein to undergo recognition by other cell surface proteins aside from DC-SIGN, thereby conferring resistance to mannan-mediated inhibition of trans-infection. Recent evidence shows that the SARS-CoV-2 spike can bind to a variety of host molecules, including neuropilin-1 (NRP1) and leucine-rich repeat-containing 15 (LRRC15) [ 42 , 82 , 83 ]. Thus, it could be possible that mutations in the Omicron BA.2 spike allow it to exhibit a higher affinity for other cell surface molecules and facilitate trans-infection mediated by other cell surface proteins.…”

“…There is mounting evidence that numerous mutations of the Omicron strain cause allosteric changes in the spike protein [ 76 , 78 , 79 , 81 ]. Because the SARS-CoV-2 spike has been shown to bind to a multitude of cell surface molecules—including sialic-acid-binding surface receptors, heparan sulfate, glycosphingolipids and more—it is plausible that the predicted unique structural dynamics of the Omicron BA.2 strain spike could confer resistance to mannan-mediated inhibition of trans-infection, as well as some ability to be captured by a fibroblast cell line that did not express DC-SIGN [ 42 , 82 , 83 ]. Most notably, Omicron mutations lead to greater spike processing by furin, which is known to reveal an epitope that is capable of being bound by the cell surface receptors neuropilin-1 (NRP1) and neuropilin-2 (NRP2) [ 119 , 120 ].…”

A special issue of IUBMB Life celebrating the 50th anniversary of FAOBMB (1972–2022)

“…This special issue also included eight review articles contributed by colleagues from the FAOBMB region 2–9 . Pore forming bacterial toxins are important virulence factors of Gram‐positive bacteria, and Michael Parker and colleagues (Bio21 Institute, University of Melbourne, Australia) review the assembly of the soluble monomeric proteins into a complex ring‐shaped pore within cholesterol rich membrane bilayers.…”

“…This special issue also included eight review articles contributed by colleagues from the FAOBMB region. 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 Pore forming bacterial toxins are important virulence factors of Gram‐positive bacteria, and Michael Parker and colleagues (Bio21 Institute, University of Melbourne, Australia) review the assembly of the soluble monomeric proteins into a complex ring‐shaped pore within cholesterol rich membrane bilayers. Recent advances of the structural features of human glucose and human monocarboxylate transporters are reviewed by Nieng Yan and colleagues (formerly at Tsinghua University, China, currently Princeton University, USA), and the structure/functional relationships of these transporters are discussed within physiological settings and their role in hyperproliferation and metabolic reprogramming of cancer cells.…”