Figure 2. Structure of SARS-CoV-2 S in the pre-fusion conformation and the genome, along with the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) S protein in complex with human ACE2. (A) Schematic of SARS-CoV-2 S primary structure colored by domain. (B) Ribbon diagrams of the SARS-CoV-2 S ectodomain cryoEM structures. (C) The SARS-CoV-2 S1 subunits. (D) The SARS-CoV-2 S2 subunits. (E) A hACE2-binding mode of SARS-CoV-2. Reproduced with permission (Wrapp et al., 2020; Walls et al., 2020; Q. Wang et al., 2020).
Accumulating evidence has revealed that SARS-CoV-2 and SARS-CoV have the same human cell receptor, the angiotensin-converting enzyme 2 (ACE2), while MERS-CoV hinges on dipeptidyl peptidase 4 for host cell entry (Wan et al., 2020). ACE2 is a type I membrane protein expressed in the lungs, hearts, kidneys, and intestines, mainly associated with cardiovascular diseases (Wan et al., 2020). A recent study analyzed the cryogenic electron microscopy structure of the SARS-CoV-2 S protein unveiled that it exhibits around 10 to 20-fold higher binding affinity to ACE2 in comparison with SARS-CoV (Berry et al., 2004). The overall replication cycle of SARS-CoV-2 is depicted in the following Figure 3.
As for the phylogenetic network analysis of SARS-CoV-2 genomes, after analysis of the sample from across the world, researchers have found three central variants differentiated through amino acid alterations, denoted A, B, and C, with A being the ancestral type in line with the bat outgroup CoV. Intriguingly, types A and C account for a considerable proportion outside East Asia ( Europe and the United States) (Forster et al., 2020). By comparison, B is the most common type in East Asia, and its ancestors ’genomes do not appear to spread outside East Asia without first mutating into a derived type B. Hence, SARS-CoV-2 genomes were found to be closely correlated, and evolutionary selection took place in human hosts, sometimes with parallel evolutionary events, where the same viral mutation occurs in two disparate human hosts (Forster et al., 2020). Owing to the erratic nature of RNA viruses as well as its high contagiousness, the continuous monitoring of SARS-CoV-2 from humans or animal species is of extreme significance for pandemic control.