Fig. 3.

Entry mechanism of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and target drugs against SARS-CoV-2: The SARS-CoV-2 enters through major routes; When angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) co-expressed on the host cell surface, SARS-CoV-2 binds to the ACE2 and get activated by TMPRSS2 via proteolytic cleavage to mediate virus-cell fusion (which can be inhibited by monoclonal antibodies, spike (S) binding protein, and small molecules). Step 1-The SARS-CoV-2 enters the host cell receptor via its spike (S) protein. After receptor binding, the SARS-CoV-2 enters the cytosol with the help of the S protein (which can be blocked by Hydroxychloroquine and Baricitinib). Once the viral genome enters the cytoplasm (Step 2) (which can be blocked by Molnupiravir), translation of the viral genome (Steps 3 & 4) occurs and forms a viral replication-transcription complex (Step 5) directly from sub-genomic RNA (+sense) (which can be blocked by Ribavirin, Remdesivir, and Favipiravir). This viral replication-transcription complex contains Envelope (E), S, and Membrane (M) proteins (which can be blocked by Oseltamivir, Ribavirin, and Favipiravir) that will translate from the RNA (Step 6) and will enter the endoplasmic reticulum (Step 6) and move to the endoplasmic reticulum-golgi intermediate compartment (ERGIC) (which can be blocked by Lepinavir) (Step 7). The viral replication-transcription complex contains nucleocapsid (proteins that interact with M proteins in the ERGIC and form a mature virion (Step 8). This mature virion will move outside the cell via the exocytic pathway (Step 9).