Transplant Drugs against SARS, MERS and COVID-19
Abstract
:1. Introduction
1.1. Pathophysiology in Coronaviral Infections
1.2. Morbidity and Mortality of Coronaviruses
1.3. Treatment of Coronaviruses
1.4. Scope of This Review
2. Methods
3. Results
4. Discussion
4.1. COVID-19 in Solid Organ Transplant Recipients
4.2. Cytokine Storm Syndrome (CSS)
4.3. Cytokine Storm Syndrome in Other Diseases
4.4. The Calcineurin/NF-AT Signaling Pathway
4.5. Two Calcineurin Inhibitors in Clinical Use
4.6. Mechanism of Action of Cyclosporin A (CsA)
4.7. Mechanism of Action of Tacrolimus
4.8. Alternative Drugs to Inhibit the Cytokine Storm Syndrome
5. Conclusions
6. Outlook
Author Contributions
Funding
Conflicts of Interest
References
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Coronaviral Serotype Studies in Humans | CNI | Remarks | Ref. No. |
MERS-CoV | Tac | renal transplant recipient on tacrolimus survived | [11] |
MERS-CoV | CsA | inhibition of viral replication | [12] |
Coronaviral Serotype Studies in Animals | CNI | Remarks | Ref. No. |
feline CoV | CsA | inhibition of viral replication in dose-dependent manner | [13] |
turkey CoV | CsA | enhanced virus titers in kidney | [14] |
Coronaviral Serotype Studies In Vitro | CNI | Remarks | Ref. No. |
MERS-CoV | CsA + IFN-α | inhibition of viral replication | [15] |
MERS-CoV, SARS-CoV | ALV | inhibition of viral replication | [16] |
SARS-CoV, CoV-229E | CsA | inhibition of viral replication SARS-CoV replication impaired, but not fully blocked (1–5% of cells remained SARS-CoV positive, even in high CsA concentrations) | [17] |
CoV-NL63, CoV-229E, SARS-CoV | CsA | inhibition of viral replication | [18] |
SARS-CoV, CoV-NL63, CoV-229E | Tac | inhibition of viral replication | [19] |
CoV-NL63 | CsA-d | inhibition of viral replication by CsA derivatives (Alisporivir, NIM811) | [19] |
SARS-CoV-2 | CsA | potent antiviral activity in SARS-CoV-2, cyclophillin depedent (and calcineurin independent) | [20] |
Research Question | Possible Answers in Literature | Refs. |
---|---|---|
Which patients with COVID-19 could benefit from the addition of CNI to the standard therapy |
| [65] |
Does CypA play a role in cardiovascular morbidity in COVID-19 patients? |
| [45] |
How to screen for patients with a high risk of progression to more severe stages of COVID-19 and thus merit pharmacological interventions |
| [67] |
Which patients with COVID-19 should be excluded from CNIs? |
| [65] |
CNI monotherapy or combination therapy with either a corticosteroid, an antimetabolite (Mycophenolate) |
| [68] |
Alternative immunomodulatory drugs? |
| [69] [70] [71] |
Alisporivir as non-immunosuppressive cyclophilin inhibitor? |
| [62,63] |
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Hage, R.; Steinack, C.; Gautschi, F.; Schuurmans, M.M. Transplant Drugs against SARS, MERS and COVID-19. Transplantology 2020, 1, 71-84. https://doi.org/10.3390/transplantology1020007
Hage R, Steinack C, Gautschi F, Schuurmans MM. Transplant Drugs against SARS, MERS and COVID-19. Transplantology. 2020; 1(2):71-84. https://doi.org/10.3390/transplantology1020007
Chicago/Turabian StyleHage, René, Carolin Steinack, Fiorenza Gautschi, and Macé M. Schuurmans. 2020. "Transplant Drugs against SARS, MERS and COVID-19" Transplantology 1, no. 2: 71-84. https://doi.org/10.3390/transplantology1020007