Fig. 2.
Life cycle of SARS-CoV-2 and potential drug targets. 1) SARS-CoV-2 enters target cells via two ways, either via endosomes or plasma membrane fusion. In both ways spike proteins (S1 e S2) mediate attachment to the cell membrane by binding to the ACE2 receptor, 2) In the endosomal via, spike proteins are activated by cathepsin L or alternatively by transmembrane protease serine 2 (TMPRSS2) in close proximity to ACE2 receptor, which initiates fusion of the viral membrane with the plasma membrane, 3) viral RNA is released and part is translated to produce polyproteins pp1a and ppab, which are cleaved by proteases PIpro and 3CLpro to yield 16 non-structural proteins that form the RNA replicase-transcriptase complex, 4) This complex drives the production of negative-sense RNAs through both replication and transcription. A subset of around 9 subgenomic RNAs including those encoding all structural proteins (S-spike, M-membrane, N-nucleocapsid and E-envelope) are translated, 5) Viral nucleocapsids are assembled from genomic RNA and N protein in the cytoplasm, followed by budding into the lumen of endoplasmic reticulum (ER)- Golgi complex, 6) Virions are then released through exocytosis. Potential SARS-CoV-2 targets and drugs are shown in red. The drugs and treatment strategies investigated aim to inhibit viral entry/replication into human cells, avoid cytokine storm or decrease hyperinflammation and lung injury. ACE - Angiotensin-Converting Enzyme, ARB – Angiotensin Receptor Blocker, CQ - Chloroquine, HQ - Hydroxychloroquine, TMPRSS2–Transmembrane serine protease 2, IL-interleukin, JAK- Janus kinase.