Fig. 1.

Representation of SARS-CoV-2 viral lifecycle and potential drug targets. 1. Binding of coronavirus to cellular receptors such as ACE-2 with host factors (such as TMPRSS2) promote viral entry via membrane fusion and endocytosis. 2. Translation of the viral RNA (polypeptide). 3. Autoproteolysis and co-translational cleavage of polypeptide to generate nsps. 4. (-Sense) subgenomic transcription and RNA replication. 5. (+sense) subgenomic transcription and RNA replication. 6. Translation of subgenomic mRNA into structural and accessory proteins. 7. Nucleocapsid buds into ERGIC studded with S, E, and M proteins. 8, 9. Finally, virions are secreted from the infected cell by exocytosis. Key compounds targeting steps that are attractive therapeutic targets are coloured in orange. ACE2, angiotensin-converting enzyme 2; nsp, non-structural proteins; S protein, spike protein; E protein, envelope protein; M protein, membrane protein; and TMPRSS2, type 2 transmembrane serine protease. Thapsigargin, a non-competitive inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), blocks the ability of the cell to pump calcium into the sarcoplasmic and endoplasmic reticulum and causes activation of UPR. Paroxetine, Parthenolide, Sertraline, and Spiperone are FDA-approved drugs that compromise ER architecture. Thapsigargin, Paroxetine, Parthenolide, Sertraline, and Spiperone are ERS pathway inhibitors and inhibit steps 4–7.