Genomic variations in SARS-CoV-2
The genome of the SARS-CoV-2 has been reported over 80% identical to the previous human coronavirus (SARS-like bat CoV) [34]. The Structural proteins are encoded by the four structural genes, including spike (S), envelope (E), membrane (M) and nucleocapsid (N) genes. The orf1ab is the largest gene in SARS-CoV-2 which encodes the pp1ab protein and 15 nsps. The orf1a gene encodes for pp1a protein which also contains 10 nsps [34], [35], [36]. According to the evolutionary tree, SARS-CoV-2 lies close to the group of SARS-coronaviruses [37], [38] (Fig. 5). Recent studies have indicated notable variations in SARS-CoV and SARS-CoV-2 such as the absence of 8a protein and fluctuation in the number of amino acids in 8b and 3c protein in SARS-CoV-2 [34] (Fig. 4 ). It is also reported that Spike glycoprotein of the Wuhan coronavirus is modified via homologous recombination. The spike glycoprotein of SARS-CoV-2 is the mixture of bat SARS-CoV and a not known Beta-CoV [38]. In a fluorescent study, it was confirmed that the SARS-CoV-2 also uses the same ACE2 (angiotensin-converting enzyme 2) cell receptor and mechanism for the entry to host cell which is previously used by the SARS-CoV [39], [40]. The single N501T mutation in SARS-CoV-2's Spike protein may have significantly enhanced its binding affinity for ACE2 [33].
Fig. 4 Betacoronaviruses genome organization; The Betacoronavirus for human (SARS-CoV-2, SARS-CoV and MERS-CoV) genome comprises of the 5′-untranslated region (5′-UTR), open reading frame (orf) 1a/b (green box) encoding non-structural proteins (nsp) for replication, structural proteins including spike (blue box), envelop (maroon box), membrane (pink box), and nucleocapsid (cyan box) proteins, accessory proteins (light gray boxes) such as orf 3, 6, 7a, 7b, 8 and 9b in the SARS-CoV-2 genome, and the 3′-untranslated region (3′-UTR). The doted underlined in red are the protein which shows key variation between SARS-CoV-2 and SARS-CoV. The length of nsps and orfs are not drawn in scale.
Fig. 5 Phylogenetic tree of coronaviruses (content in red is the latest addition of newly emerged SARS-CoV-2 and WSFMP Wuhan-Hu-1 is used as a reference in the tree); The phylogenetic tree showing the relationship of Wuhan-Hu-1 (denoted as red) to selected coronavirus is based on nucleotide sequences of the complete genome. The viruses are grouped into four genera (prototype shown): Alphacoronavirus (sky blue), Betacoronavirus (pink), Gammacoronavirus (green) and Deltacoronavirus (light blue). Subgroup clusters are labeled as 1a and 1b for the Alphacoronavirus and 2a, 2b, 2c, and 2d for the Betacoronavirus. This tree is based on the published trees of Coronavirinae [3], [41] and reconstructed with sequences of the complete RNA- dependent RNA polymerase- coding region of the representative novel coronaviruses (maximum likelihood method using MEGA 7.2 software). severe acute respiratory syndrome coronavirus (SARS- CoV); SARS- related coronavirus (SARSr- CoV); the Middle East respiratory syndrome coronavirus (MERS- CoV); porcine enteric diarrhea virus (PEDV); Wuhan seafood market pneumonia (Wuhan-Hu-1). Bat CoV RaTG13 Showed high sequence identity to SARS-CoV-2 [42].