Abstract
The novel coronavirus originated in December 2019 in Hubei, China. This contagious disease named as COVID-19 resulted in a massive expansion within 6 months by spreading to more than 213 countries. Despite the availability of antiviral drugs for the treatment of various viral infections, it was concluded by the WHO that there is no medicine to treat novel CoV, SARS-CoV-2. It has been confirmed that SARS-COV-2 is the most highly virulent human coronavirus and occupies the third position following SARS and MERS with the highest mortality rate. The genetic assembly of SARS-CoV-2 is segmented into structural and non-structural proteins, of which two-thirds of the viral genome encodes non-structural proteins and the remaining genome encodes structural proteins. The most predominant structural proteins that make up SARS-CoV-2 include spike surface glycoproteins (S), membrane proteins (M), envelope proteins (E), and nucleocapsid proteins (N). This review will focus on one of the four major structural proteins in the CoV assembly, the spike, which is involved in host cell recognition and the fusion process. The monomer disintegrates into S1 and S2 subunits with the S1 domain necessitating binding of the virus to its host cell receptor and the S2 domain mediating the viral fusion. On viral infection by the host, the S protein is further cleaved by the protease enzyme to two major subdomains S1/S2. Spike is proven to be an interesting target for developing vaccines and in particular, the RBD-single chain dimer has shown initial success. The availability of small molecules and peptidic inhibitors for host cell receptors is briefly discussed. The development of new molecules and therapeutic druggable targets for SARS-CoV-2 is of global importance. Attacking the virus employing multiple targets and strategies is the best way to inhibit the virus. This article will appeal to researchers in understanding the structural and biological aspects of the S protein in the field of drug design and discovery.
Highlights
Coronaviruses (CoVs) are pathogens from the Coronaviridae family and have an impact on human and animal health; in particular their respiratory and gastrointestinal tract system whose symptoms range from mild to lethal (Ghosh et al, 2020)
Almost a decade passed since the outbreak of SARS-CoV, the subsequent zoonotic coronavirus MERS-CoVs emerged in Saudi Arabia with 2494 cases and 858 deaths (Source: WHO)
To inhibit the virus progression, several key steps have been identified in the virus life cycle; 1) receptor binding domain (RBD) binding which plays an important role in the viral fusion to host cells, 2) protease enzymes in synthesizing RNA-dependent RNA polymerase, and 3) RNA-dependent RNA polymerase for transcription
Summary
Coronaviruses (CoVs) are pathogens from the Coronaviridae family and have an impact on human and animal health; in particular their respiratory and gastrointestinal tract system whose symptoms range from mild to lethal (Ghosh et al, 2020). Among these six human-CoVs, SARS- and MERS- CoVs are extremely pathogenic and the transmission within humans generally occurs via close contact through the inhalation of respiratory droplets or sneezing, similar to influenza and other respiratory pathogens (Pillaiyar et al, 2016; Ghosh et al, 2020). At the end of 2002, the outbreak of SARS in Guangdong province in China registered 8098 cases with 774 deaths. Almost a decade passed since the outbreak of SARS-CoV, the subsequent zoonotic coronavirus MERS-CoVs emerged in Saudi Arabia with 2494 cases and 858 deaths (Source: WHO). Until now (as of December 2, 2020, WHO) the 2019-nCoV had spread rapidly in over 220 countries and registered over 63,360,234 reported cases and 1,475,825 deaths (https://www.who.int/emergencies/ diseases/novel-coronavirus-2019)
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