Fig. 2.

Entry, replication, and productive infection establishment by the SARS-CoV2 in humans. The SARS-CoV2 enters and infects the ciliated epithelial cells (nasal or pulmonary epithelial cells primarily) via the interaction of its S protein with the ACE2 receptors of the host cells. The interaction is mediated by S1 protein that generates due to cleavage of S protein into S1 and S2 by the furin or PCSK3. The furin acts on the PRAR, a dibasic furin binding site at the S protein. The S2 protein bins to the TMPRSS, which further increases the SARS-CoV2 entry in the host cell. SARS-CoV2 also enters the cell through CD147 as the mAb, meplazumab against it inhibits the severity and symptoms of COVID-19. SARS-CoV2 and ACE2 interaction promotes its cellular endosomal entry via cathepsin-L-dependent endocytosis. TPC2 on early endosome and lysosome, and PIKfyve on early endosome also play a crucial role in virus entry in the endosome via maintaining endolysosomal homeostasis. The IFITM3 on endosomes fuse with the SARS-CoV2 to enhance its trafficking to the lysosomes. The endosomes fuse with lysosomes to form endolysosomes or autolysosomes containing the virion. On the other hand, the interaction between LC3-II of the phagophore and Nsp8 forms the autophagosome containing virus. The autophagosome fuses with lysosomes to form autophagolysosomes or autolysosomes. The ssRNA of ORF1a and ORF1b release in the cytosol and translate into polyprotein 1a (PP1a) and PP1b synthesizing 15Nsps, which form RTC. The RTC forms full length genomic and subgenomic RNAs, which form the virion that via endoplasmic reticulum (ER) to Golgi apparatus ERGIC. The virion in the vesicle comes out form the cell via exocytosis.