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Table 1 Possible targets to alleviate the life-threatening complications of COVID-19

From: Insights to SARS-CoV-2 life cycle, pathophysiology, and rationalized treatments that target COVID-19 clinical complications

Pre-Phase 1
- Vaccine (e.g., against the SARS-CoV-2 S protein) 1
(for the various technologies employed see also text and [149,150,151,152])
Phase 1 of the disease: Life cycle of the virus (extracellular – early steps of infection)
- SARS-CoV-2 neutralizing monoclonal antibodies 1
(see text and [153,154,155]; because antibody-dependent enhancement of disease [156] cannot be reliably predicted after either vaccination or treatment with antibodies, the on-going clinical trials for COVID-19 immune interventions should depend on careful analyses for safety in humans; also, preferentially the development of neutralizing antibodies after vaccination should be monitored) – (neutralizing antibodies from Eli Lilly and Regeneron Pharmaceuticals Inc. have received FDA emergency use authorization and GlaxoSmithKline/Vir Biotechnology has moved an anti-SARS-CoV-2 mAb into Phase 3 clinical trials)
- Soluble ACE2 (decoy for virus) 2
(a recent development is this field is the production of engineered human ACE2 with optimum binding to the S protein of SARS-CoV-2 [157])
- Antibodies or small molecules that target ACE2 2
- Treatments that suppress ACE2 and/or TMPRSS2 genes expression 2
- TMRPSS2 protease inhibitors 3
- Inhibitors of membrane fusion and/or clathrin-mediated endocytosis 4
Phase 1 of the disease: Life cycle of the virus (intracellular)
- Tubulin polymerization inhibitors 4,4*,7
- Inhibitors of the endosomal/lysosomal compartments 4,4*
(recent studies in non-human primates do not support the use of hydroxychloroquine -either alone or in combination with azithromycin- for the treatment of COVID-19 in humans [158]; also, chloroquine was not found to inhibit infection of human lung cells with SARS-CoV-2 [159])
- CTSB/L specific inhibitors 4
- Small molecule inhibitors of cellular pathways reshaped by SARS-CoV-2 infection
(not shown)
- Inhibitors of the virus’ main protease 5,6
- Virus’ RNA-dependent RNA polymerase inhibitors 5,6
- MHC class II/MHC class I antigen presentation enhancement 8
Phase 2 of the disease: adverse effects of COVID-19
- ACE inhibitors, AT1R blockers 1012
- The ANG(1–7) peptide (or non-peptide analogs) 1012
- Antioxidants or radical scavengers 1012
- Adjunct immunotherapies (or corticosteroids) to mitigate “cytokine storm” (e.g., inhibition of IL-6 signaling) 1012
(notably, the use of hydrocortisone [160] or dexamethasone [161] showed some beneficial effects on mortality, organ support, days alive and free of mechanical ventilation in patients with severe COVID-19)
- Anticoagulant medications to alleviate intravascular coagulation
(not shown)
- Additional life-supporting measures (e.g., ventilation or intubation)
(not shown)
  1. Numbers in bold italics (see, respective red color numbers in Figs. 1, 2) indicate major components in SARS-CoV-2 life cycle and in COVID-19 progression and pathology