ABSTRACT

The outbreak of a novel coronavirus (SARS-CoV2) associated with acute respiratory disease called COVID-19 marked the introduction of the third spillover of an animal CoV to humans in the last two decades. Currently, there is no specific drug or vaccine against this deadly virus; therefore, there is a pressing need to understand the mechanism through which this virus enters the host cell. Viral entry into the host cell is a multistep process in which SARS-CoV-2 utilizes the receptor binding domain of the spike glycoprotein (S) to recognize ACE2 receptors on the human cells; this initiates the host cell entry by promoting the viral-host cell membrane fusion through large scale conformational changes in the S protein. Receptor recognition and fusion are critical and essential steps of viral infections and are key determinants of the viral host range and cross-species transmission. Form the current origin the SARS-CoV2 genome analysis with various bioinformatics tools revealed that it belongs to beta CoVs genera, with highly similar genome as bat coronavirus and receptor binding domain (RBD) of spike glycoprotein as Malayan pangolin coronavirus. Based on its genetic proximity, SARS-CoV2 is likely to be originated from bat derived CoV and transmitted to humans via an unknown intermediate mammalian host, probably Malayan pangolin. Further spike protein S1/S2 cleavage site of SARS-CoV2 has acquired polybasic furin cleavage site which is absent in bat and pangolin suggesting natural selection either in an animal host before zoonotic transfer or in humans following zoonotic transfer.

The focus of this chapter is to recapitulate a preliminary opinion about the disease, origin and life cycle of SARS-CoV2, roles of virus proteins in pathogenesis, commonalities and discuss the receptor recognition mechanisms of coronaviruses. In addition chapter covers a comparative analysis of the SARS-CoV and SARS-CoV2 S proteins, receptor-binding specificity, and discuss the differences in their antigenicity based on biophysical and structural characteristics.