Glycans of SARS-CoV-2 Spike Protein in Virus Infection and Antibody Production

Abstract

Viral protein glycosylation represents a successful strategy employed by the parasite to take advantage of host–cell machinery for modification of its own proteins. The resulting glycans have unneglectable roles in viral infection and immune response. The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which presents on the surface of matured virion and mediates viral entry into the host, also undergoes extensive glycosylation to shield it from the human defense system. It is believed that the ongoing COVID-19 pandemic with more than 90,000,000 infections and 1,900,000 deaths is partly due to its successful glycosylation strategy. On the other hand, while glycan patches on S protein have been reported to shield the host immune response by masking “nonself” viral peptides with “self-glycans,” the epitopes are also important in eliciting neutralizing antibodies. In this review, we will summarize the roles of S protein glycans in mediating virus–receptor interactions, and in antibody production, as well as indications for vaccine development.

The glycosylation in SARS-CoV-2 and its receptor ACE2

“… 54 Compared with Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV, the S protein of SARS-CoV-2 has a lower glycosylation density, 35 , 63 , 327 indicating the S protein surface is more exposed and it is more effective in eliciting humoral immunity. 31 Since the first report of 16 N-linked glycosites by cryo-electron microscopy (cryo-EM), 320 the characterization of glycosylation of S protein becomes a hotspot. 38 , 62 , 63 , 70 , 145 , 328 – 336 In total, 23 N-linked glycosites with high occupancy (mostly >95%) have been reported (Fig.…”

Modulation of Host Immune Response Is an Alternative Strategy to Combat SARS-CoV-2 Pathogenesis

“…From this, one can speculate why the virus has a high rate of transmission ( 27 ). Numerous studies have reported a glycan shield over the spike protein that might be somehow helping in the immunity evasion of the virus, but further work is still needed o confirm its role in immunity evasion ( 28 , 29 ). There is much more that needs to be discovered about this spike protein.…”

Structural Insight into the Binding of Cyanovirin-N with the Spike Glycoprotein, Mpro and PLpro of SARS-CoV-2: Protein–Protein Interactions, Dynamics Simulations and Free Energy Calculations

“…In vitro and in vivo experiments later revealed antiviral activity of cyanovirin-N against the Zaire strain of the Ebola virus (ZEBOV) based on its affinity towards envelope glycoproteins on the surface of the Ebola virus [40]. Pathogenic viruses take control of the host's cellular apparatus to implement their own replication processes, a strategy fortified by glycosylation [41]. The SARS-CoV-2 spike protein undergoes glycosylation to produce glycans that mask polypeptide epitopes and shield it from the innate immune response, and facilitate spike-ACE2 interaction [41,42].…”

“…Pathogenic viruses take control of the host's cellular apparatus to implement their own replication processes, a strategy fortified by glycosylation [41]. The SARS-CoV-2 spike protein undergoes glycosylation to produce glycans that mask polypeptide epitopes and shield it from the innate immune response, and facilitate spike-ACE2 interaction [41,42]. The glycosylation of the SARS-CoV-2 spike protein produces 22 N-linked glycosylation sites that comprise two oligomannose-type, six oligomannose and complex-type and 14 complextype glycans [43,44].…”

“…The glycosylation of the SARS-CoV-2 spike protein produces 22 N-linked glycosylation sites that comprise two oligomannose-type, six oligomannose and complex-type and 14 complextype glycans [43,44]. In SARS-CoV-2, glycans play a significant role at the interface of the spike-ACE2 interaction and are possible drug targets that could reduce binding to ACE2 and subsequent cell-cell transmission [41]. Mazur-Marzec and colleagues comprehensively reviewed the antiviral activities of cyanovirin-N and detailed broad-spectrum activity against viruses including human herpes 6, measles, hepatitis, and the influenza virus, all of which comprise N-linked mannose oligosaccharide glycans [45].…”