Chapter 6

Biochemical Characterization of SARS-CoV-2 Spike Protein Proteolytic Processing

Hayat Khan*, Firasat Hussain*, Muhammad Kalim, Shafi Ullah, Kashif Rahim and Faisal Siddique

Abstract

Coronavirus spike (S) glycoproteins belong to class I viral fusion protein. Spike protein has S1 and S2 domain that respectively are involved in receptor-binding and fusion of virus-host membrane. Spike protein of SARS-CoV-2 interacts with human angiotensin-converting enzyme-2 (hACE-2), expressing predominantly on the lungs and intestinal cells as a receptor. Although the receptor-binding motif of SARSCoV- 2 shares only 50% homology with that of SARS-CoV, its affinity towards hACE- 2 are many folds higher. The host proteases mediate the membrane fusion reaction through the cleavage of S protein between S1 and S2. The S of SARS-CoV-2 harbors cleavage site for furin or furin-like protease, which sets the SARS-CoV-2 apart from SARS and SARS-like other coronaviruses. The S protein is cleaved either by one or several host proteases depending upon the infecting cells and virus strains. Based on the presence of a different type of host protease, the CoVs decides whether to enter cells via the cell membrane route or endocytosis. Unlike SARS-CoV, S of SARS-Co- -2 causes typical syncytium formation (cell-cell fusion) among the infected cells. Besides receptor binding, S protein is a major target of neutralizing antibodies following infection. However, antibodies raised against SARS-CoV either weakly or fail to neutralize the SARS-CoV-2, suggesting no cross-protection between them. Being is a driver of viral entry, the spike protein of SARS-CoV-2 is a good candidate for vaccine development. Furthermore, the role of host proteases in the membrane is also very significant for the designing of entry inhibitors. The purpose of this chapter is to summarize the detailed structure, fusogenic potential, protease-driven activation, and cross-neutralization of spike protein with antibodies from SARS-CoV and sera of recovered patients.

Total Pages: 162-194 (33)

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