The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens

Abstract

The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a grave threat to global public health and imposes a severe burden on the entire human society. Like other coronaviruses, the SARS-CoV-2 genome encodes spike (S) glycoproteins, which protrude from the surface of mature virions. The S glycoprotein plays essential roles in virus attachment, fusion and entry into the host cell. Surface location of the S glycoprotein renders it a direct target for host immune responses, making it the main target of neutralizing antibodies. In the light of its crucial roles in viral infection and adaptive immunity, the S protein is the focus of most vaccine strategies as well as therapeutic interventions. In this review, we highlight and describe the recent progress that has been made in the biosynthesis, structure, function, and antigenicity of the SARS-CoV-2 S glycoprotein, aiming to provide valuable insights into the design and development of the S protein-based vaccines as well as therapeutics.

Microsecond simulations and CD spectroscopy reveals the intrinsically disordered nature of SARS-CoV-2 Spike-C-terminal cytoplasmic tail (residues 1242-1273) in isolation

“…RBM is present as an extended loop insertion which binds to bottom side of the small lobe of ACE2 receptor. RBD further consists of two subdomains: an external and a core subdomain which engages with the target receptor (2,7). Several detailed crystallographic structures of SARS-CoV-2 RBD in complex with ACE2 are available on protein data bank revealing the network of key hydrophilic interactions (6,8).…”

“…The S2 subunit (residues 686-1273) has a hydrophobic fusion peptide, two heptad repeats, a transmembrane domain, and a cytoplasmic C-terminal tail (Figure 1). After virus attachment on host cellular membrane, S2 subunit enclosing a fusion machinery mediates the fusion of host cell and viral membranes (2,9).…”

Coevolutionary Analysis and Perturbation-Based Network Modeling of the SARS-CoV-2 Spike Protein Complexes with Antibodies: Binding-Induced Control of Dynamics, Allosteric Interactions and Signaling

“…SARS-CoV-2 infection is transmitted when the viral spike (S) glycoprotein binds to the host cell receptor leading to the entry of S protein into host cells and membrane fusion. [6][7][8] The full-length SARS-CoV-2 S protein consists of two main domains, amino (N)-terminal S1 subunit and carboxyl (C)-terminal S2 subunit. The subunit S1 is involved in the interactions with the host receptor and includes an Nterminal domain (NTD), the receptor-binding domain (RBD), and two structurally conserved subdomains (SD1 and SD2).…”

Platforms Exploited for SARS-CoV-2 Vaccine Development

“…Furthermore, for membrane fusion, the SARS-CoV-2 spike requires to be proteolytically cleaved at the S1/S2 boundary in such a way that S1 dissociates, and S2 undergoes a structural change [ 8 ]. These features of SARS-CoV-2 entry contribute to its rapid spread, severe symptoms, and high fatality rates of infected patients [ 9 , 10 ]. As of 8 September 2020, SARS-CoV-2 had infected over 28 million people in 216 countries/territories, causing over 906 thousand fatalities [ 11 ].…”