An Overview of Spike Surface Glycoprotein in Severe Acute Respiratory Syndrome–Coronavirus

Abstract

The novel coronavirus originated in December 2019 in Hubei, China. This contagious disease named as COVID-19 resulted in a massive expansion within 6 months by spreading to more than 213 countries. Despite the availability of antiviral drugs for the treatment of various viral infections, it was concluded by the WHO that there is no medicine to treat novel CoV, SARS-CoV-2. It has been confirmed that SARS-COV-2 is the most highly virulent human coronavirus and occupies the third position following SARS and MERS with the highest mortality rate. The genetic assembly of SARS-CoV-2 is segmented into structural and non-structural proteins, of which two-thirds of the viral genome encodes non-structural proteins and the remaining genome encodes structural proteins. The most predominant structural proteins that make up SARS-CoV-2 include spike surface glycoproteins (S), membrane proteins (M), envelope proteins (E), and nucleocapsid proteins (N). This review will focus on one of the four major structural proteins in the CoV assembly, the spike, which is involved in host cell recognition and the fusion process. The monomer disintegrates into S1 and S2 subunits with the S1 domain necessitating binding of the virus to its host cell receptor and the S2 domain mediating the viral fusion. On viral infection by the host, the S protein is further cleaved by the protease enzyme to two major subdomains S1/S2. Spike is proven to be an interesting target for developing vaccines and in particular, the RBD-single chain dimer has shown initial success. The availability of small molecules and peptidic inhibitors for host cell receptors is briefly discussed. The development of new molecules and therapeutic druggable targets for SARS-CoV-2 is of global importance. Attacking the virus employing multiple targets and strategies is the best way to inhibit the virus. This article will appeal to researchers in understanding the structural and biological aspects of the S protein in the field of drug design and discovery.

Expression of plasma IFN signaling-related miRNAs during acute SARS-CoV-2 infection and its association with RBD-IgG antibody response

“…Currently, a large number of studies have reported that the interaction between RBD located at the spike protein of SARS-CoV-2 and the receptor ACE2 on host cells is essential for viral entry [ 26 , 27 ]. Moreover, antibodies against RBD at the recovery phase of COVID-19 present neutralizing activity because they can block the interaction between ACE2 and viral spike protein [ 28 ].…”

Structure and Mutations of SARS-CoV-2 Spike Protein: A Focused Overview

“… 106 Coronaviruses consist of four main structural proteins, with the membrane (M), envelope (E), and nucleocapsid (N) proteins in addition to the S-protein of focus in the present paper. 107 …”

“…SARS-CoV-2 is the seventh coronavirus known to infect Homo sapiens , the others being the common-cold causing HCoV-229E, HCoV-NL63, HCoV-HKU1, and HCoV-OC43, as well as the more pathogenic SARS-CoV-1 and MERS-CoV. , While some of the milder of these are α-coronaviruses and some β-coronaviruses (OC43, HKU1), all the three most pathogenic viruses are β-coronaviruses with distinct functional properties . Coronaviruses consist of four main structural proteins, with the membrane (M), envelope (E), and nucleocapsid (N) proteins in addition to the S-protein of focus in the present paper …”

“…Taking the wider perspective of other human-host coronaviruses (Table ) and other spike protein structures (Table ), several mutations in the SARS-CoV-2 RBD have contributed to a stronger affinity toward ACE2 . Indeed, by far the most sequence variation between SARS-CoV-1 and SARS-CoV-2 occurs in the S1 domain that includes the RBD. , In addition, the highly positively charged amino acid sequence RRAR represents a new furin-like cleavage site that is not seen in other related β-coronaviruses. , Many sequence parts of the RBD of these viruses show similarity both to nonhuman but also human protein motifs, which may help to understand protein–protein interactions with the S-protein more broadly …”

“…106 Coronaviruses consist of four main structural proteins, with the membrane (M), envelope (E), and nucleocapsid (N) proteins in addition to the S-protein of focus in the present paper. 107 Compared to some other mRNA viruses, which generally have very high mutation rates, coronaviruses tend to evolve several-fold more slowly due to their proof-reading machinery, 108 of the order of 10 −4 substitutions per site per year. 105,109 SARS-CoV-2 is currently evolving substantially faster than this (albeit still slowly compared to other nonproofed mRNA viruses), estimated at 7 × 10 −4 substitutions per site per year (2 × 10 −6 per day), 8 and has seen a remarkable lineage evolution during the pandemic, as expected from its high prevalence and ongoing adaptation to humans.…”