Fig. 1

The RNA genome organization of SARS-CoV-2 is shown to decipher the entry and pathogenesis of the virus. SARS-CoV-2 enters the nasopharyngeal tract through the respiratory droplets ejected from coughing or sneezing by another person(s) in close contact. As shown, the hemagglutinin-esterase (HE) (1) acts as a hemagglutinin (HA), (2) it binds sialic acids (SA) on the surface glycoproteins, and (3) contains acetyl-esterase activity triggering the viral spike (S) protein-mediated host cell entry and subsequent proliferation across the mucosa. The nucleocapsid (N) protein works on two specific RNA substrates: (1) the transcriptional regulatory sequences (TRSs) and (2) the genomic packaging signal. Once inside the host membrane, the virus travels down bronchial tubes to the lungs; and as a result, the lining of the respiratory tree becomes injured which in turn irritates the nerves of the lining of the airway; and the resultant impact is the inflammation and hardening of the mucus membrane of the lungs making difficult to supply oxygen to the blood instigating the increased shortness of breath. The significant increase in the pro-inflammatory cytokines and chemokines (including IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1α, and TNFα), i.e., the cytokine storm has been shown to induce the local inflammation generating the severe onset of the disease