Spike Glycoprotein Is Central to Coronavirus Pathogenesis-Parallel Between m-CoV and SARS-CoV-2

Abstract

Coronaviruses (CoVs) are single-stranded, polyadenylated, enveloped RNA of positive polarity with a unique potential to alter host tropism. This has been exceptionally demonstrated by the emergence of deadly virus outbreaks of the past: Severe Acute Respiratory Syndrome (SARS-CoV) in 2003 and Middle East Respiratory Syndrome (MERS-CoV) in 2012. The 2019 outbreak by the new cross-species transmission of SARS-CoV-2 has put the world on alert. CoV infection is triggered by receptor recognition, membrane fusion, and successive viral entry mediated by the surface Spike (S) glycoprotein. S protein is one of the major antigenic determinants and the target for neutralizing antibodies. It is a valuable target in antiviral therapies because of its central role in cell-cell fusion, viral antigen spread, and host immune responses leading to immunopathogenesis. The receptor-binding domain of S protein has received greater attention as it initiates host attachment and contains major antigenic determinants. However, investigating the therapeutic potential of fusion peptide as a part of the fusion core complex assembled by the heptad repeats 1 and 2 (HR1 and HR2) is also warranted. Along with receptor attachment and entry, fusion mechanisms should also be explored for designing inhibitors as a therapeutic intervention. In this article, we review the S protein function and its role in mediating membrane fusion, spread, tropism, and its associated pathogenesis with notable therapeutic strategies focusing on results obtained from studies on a murine β-Coronavirus (m-CoV) and its associated disease process.

Lactoferrin Binding to SARS-CoV-2 Spike Glycoprotein Blocks Pseudoviral Entry and Relieves Iron Protein Dysregulation in Several In Vitro Models

“…Although the receptor-binding domains of Spike from SARS-CoV-2 and SARS-CoV share ca. 75% amino acid identity, the two viruses show significant differences in their ability to infect and transmit in humans [ 44 ]. Interestingly, recent papers have highlighted the possible role of Spike in contributing to the higher virulence of SARS-CoV-2 [ 44 ].…”

“…75% amino acid identity, the two viruses show significant differences in their ability to infect and transmit in humans [ 44 ]. Interestingly, recent papers have highlighted the possible role of Spike in contributing to the higher virulence of SARS-CoV-2 [ 44 ]. Indeed, Spike is emerging as the main virulence factor of SARS-CoV-2, able to induce host immunopathogenesis, which is, in turn, the critical regulator of virus infection and disease outcomes [ 44 ].…”

“…Interestingly, recent papers have highlighted the possible role of Spike in contributing to the higher virulence of SARS-CoV-2 [ 44 ]. Indeed, Spike is emerging as the main virulence factor of SARS-CoV-2, able to induce host immunopathogenesis, which is, in turn, the critical regulator of virus infection and disease outcomes [ 44 ]. For this reason, all efforts in the last two years have focused on discovering substances capable of interacting with Spike and, in turn, inhibiting SARS-CoV-2 infection.…”

The First Approved COVID-19 Vaccines: The Road to Cancer Vaccines

“…Various studies concluded that SARS-CoV-2 is 80% genetically identical to SARS-CoV. Therefore, the selection of spike protein as the antigen target was well supported by previous studies and lessons from these two coronaviruses [11,12]. In addition, the prefusion stabilization strategy was also previously developed and established for the respiratory syncytial virus (RSV) MERs vaccines [13,14].…”

Neurotropic Virus-Induced Meningoencephalomyelitis

“…MHV can infect the CNS and cause white matter lesions, which makes it an excellent viral model of neuroinflammatory demyelinating disease. Depending on the inoculation route and the strain of MHV-CoV, different outcomes are expected [21].…”