Coronavirus Spike (S) Protein: A Brief Review on Structure-Function Relationship, Host Receptors, and Role in Cell Infection

Abstract

Coronaviruses (CoVs) are a broad group of spherical and enveloped viruses that cause diseases in humans and animals. CoVs have become a major threat to public health in the past two decades, exemplified by epidemics of acute respiratory syndromes and, most recently, the coronavirus disease 2019 pandemic. The envelope of CoVs contains spike (S) proteins, which are transmembrane proteins with a crown-like shape involved in cell attachment, cell‒cell fusion, host tropism, and pathogenesis. The receptors for spike proteins in host cells can be glycans and proteins. This review approaches the structural and functional aspects of the S protein of CoVs. Several issues are presented, including the structure‒function relationship, examples of host receptors, S protein-host cell connection, and its role in the entry of the virus into host cells. The S protein is one of the main targets of studies on the evolutionary relationships between CoVs, mapping of cross-host transmission events, changes in virulence, variations in disease severity level, and the development of therapeutic strategies and vaccines.

Plant Molecular Pharming and Plant-Derived Compounds towards Generation of Vaccines and Therapeutics against Coronaviruses

“…Decision-tree experiments based on mathematical modeling have revealed notable characteristics of the amino acid sequence of the SARS-CoV-2, which is distinct from that of MERS-CoV. Coronaviruses possess similar S proteins that bind to their respective host cells and, additionally, they use the same host protease for activating their S proteins [42].…”

Detection of SARS-CoV-2 by using real-time PCR nasopharyngeal swabs in suspected patients and their clinical medication

“…In the case of beta coronaviruses there exist spike protein (S), a small membrane protein (SM) and the glycoprotein (M) as well as an additional membrane protein. The genome of the SARS-COV-2 is 96% similar to the whole genome of bat corona virus [ 2 , 6 ].…”

Virus-Mediated Cell-Cell Fusion

“…Coronaviridae are a family of viruses first characterized in humans in late 1960s which has recently become an increasingly severe threat to global public health, exemplified by the previous outbreaks of Severe Acute Respiratory Syndrome CoV (SARS-CoV) in 2001 and Middle East Respiratory Syndrome CoV (MERS-CoV) in 2012, but especially by the current COVID-19 pandemic induced by SARS-CoV-2 which is responsible for hundreds of thousands of people deaths worldwide [ 104 ]. CoVs are enveloped viruses with a positive single-strand RNA genome of around 30 kb in length that encodes for four main viral proteins, the spike protein (S) involved in viral entry, the membrane protein (M), the envelope protein (E) required for virus assembly and release, and the nucleocapsid proteins (N) [ 105 ].…”

“…The virus-cell fusion process begins with cleavage of the S protein by cellular proteases that yields the receptor binding domain of S1 and the fusion domain of S2, which is sometimes subsequently again cleaved to generate and expose the fusion peptide directly involved in fusion of the viral and cellular membranes [ 116 , 117 , 118 ]. CoVs can recognize different cell surface molecules as their host cell receptors, including proteins, sugars, and heparan sulfate depending of viral sub-families and the receptor binding domains (RBD) of the S spike [ 104 ]. Remarkably, CoVs usually can adapt and change receptors for virus cellular entry in the new host either by genetic mutation or recombination to infect a new host species [ 119 ].…”