Prospect of SARS-CoV-2 spike protein: Potential role in vaccine and therapeutic development

Abstract

The recent outbreak of the betacoronavirus SARS-CoV-2 has become a significant concern to public health care worldwide. As of August 19, 2020, more than 22,140,472 people are infected, and over 781,135 people have died due to this deadly virus. In the USA alone, over 5,482,602 people are currently infected, and more than 171,823 people have died. SARS-CoV-2 has shown a higher infectivity rate and a more extended incubation period as compared to previous coronaviruses. SARS-CoV-2 binds much more strongly than SARS-CoV to the same host receptor, angiotensin-converting enzyme 2 (ACE2). Previously, several methods to develop a vaccine against SARS-CoV or MERS-CoV have been tried with limited success. Since SARS-CoV-2 uses the spike (S) protein for entry to the host cell, it is one of the most preferred targets for making vaccines or therapeutics against SARS-CoV-2. In this review, we have summarised the characteristics of the S protein, as well as the different approaches being used for the development of vaccines and/or therapeutics based on the S protein.

Keywords: COVID-19; SARS-CoV-2; Spike protein; Therapeutic; Vaccine.

Fig. 1

Structure of SARS-CoV-2 Spike protein RBD bound with ACE2A. Schematic representation of SARS-CoV-2 Spike protein. Linear representation of the SARS-CoV-2 spike monomer. Its S1 subunit contains the N-terminal domain (NTD; 14–305 aa), receptor binding domain (RBD; 319–541 aa), and receptor binding motif (RBM; 437–508 aa). Its S2 subunit contains fusion peptide (FP; 788–806 aa), heptad repeat 1 (HR1;12–984 aa), heptad repeat 2 (HR2;1163–1213 aa), transmembrane domain (TM;1214–1237 aa), and cytoplasmic domain (CP; 1238–1273). The predicted glycosylation sites are indicated above the domain bars. B. Overall structure of the SARS-CoV-2 RBD bound to ACE2. ACE2 is shown in lime green. The SARS-CoV-2 RBD core is shown in purple and RBM in tint colour. The N-terminal helix of ACE2 responsible for binding is labelled (Lan et al., 2020).

Fig. 2

Schematic representation of antibody-dependent enhancement and protection through nanobodies. A. Virus particles are detected by heterotypic antibodies from previous infection. This complex then binds to the Fcγ receptor on the surface of immune cells and is internalized. Further virus replication leads to an increased viral load. B. The nanobody lacks an Fc portion and is unable to bind to the Fcγ receptor, which protects the cell from antibody-dependent enhancement (created with BioRender.com).