Chasing COVID-19 through SARS-CoV-2 spike glycoprotein

Abstract

An ongoing pandemic Coronavirus disease (COVID-19), caused by a newly emerged Coronavirus, SARS-CoV-2 has affected millions of people globally. One of the most crucial structural proteins of SARS-CoV-2 is the Spike glycoprotein (S-glycoprotein), for which the first de novo modelling was envisaged by our group in early 2020, and was superimposed to its predecessor SARS-CoV S-glycoprotein, to determine structural divergence, glycosylation and antigenic variation between SARS-CoV-2 and SARS-CoV. S-glycoprotein is involved in binding with the cellular receptor, membrane fusion, internalization via angiotensin-converting enzyme 2 (ACE2) receptor, and tissue tropism. Upon internalization into the target host cells, the viral genome encodes two precursor polypeptides which get processed into 16 mature nonstructural proteins that play a crucial role in replication and transcription of SARS-CoV-2. Currently S-glycoprotein is one of the most vital targets for vaccine and therapeutics development for COVID-19.

Keywords: ACE-2 receptor; COVID-19; SARS-CoV-2; Spike glycoprotein; Virus-host interaction.

Fig. 1

Representation of the genomic organization of the SARS-CoV-2 and domain structure of Spike glycoprotein (A). S-glycoprotein contains S1 and S2 subunits where S1 subunit consists of signal sequence, N-terminal domain (NTD) and receptor binding domain (RBD). The S2 subunit consists of heptad-repeat (HR) regions as HR-N and HR-C involves the formation of coiled coil structure within the protein ectodomain. At the interface of S1 and S2 subunit various cleavage sites are present including protease, furin and S2′ protease. S- Spike glycoprotein gene, E-Envelope protein gene, N- nucleocapsid protein gene, M- membrane protein gene, RBD- receptor-binding domain. Structural comparison of Spike glycoprotein of SARS-CoV-2 (B), with SARS-CoV (C), suggesting minimal structural difference in superimposed spike glycoproteins structures (D)

Fig. 2

Structure of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and interaction with host cellular receptor ACE2. SARS-CoV-2 encodes for four structural proteins, spike glycoprotein, membrane glycoprotein (M), Envelope (E), nucleocapsid (N). Spike glycoprotein is embedded in the host derived membrane which binds with the host cell receptor ACE2. The inset is showing the protein–protein interaction of SARS-CoV-2 S-glycoprotein with host cell receptor ACE2 mediated via receptor binding domain (RBD) present in spike glycoprotein and peptidase domain of ACE2