4.4 Review

The treatment of SARS-CoV2 with antivirals and mitigation of the cytokine storm syndrome: the role of gene expression

Journal

GENOME
Volume 64, Issue 4, Pages 400-415

Publisher

CANADIAN SCIENCE PUBLISHING
DOI: 10.1139/gen-2020-0130

Keywords

SARS-CoV2; epigenetics; gene expression; drug treatment; cytokine release syndrome; cytokine storm syndrome

Funding

  1. Natural Sciences and Engineering Research Council (NSERC) of Canada [RGPIN-2017-05927]
  2. CancerCare Manitoba Foundation [761020318]
  3. Research Manitoba/CancerCare Manitoba Master's Studentship Award
  4. University of Manitoba Graduate Fellowship
  5. Canadian Institutes of Health Research grant [154043]
  6. NSERC [RGPIN-2015-06543]

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This article discusses antiviral treatments for SARS-CoV2 and treatment strategies for the CSS. It compares antivirals with in vitro activity against SARS-CoV2, SARS-CoV1 and MERS-CoV, and discusses medications that reduce the effects or expression of cytokines involved in the CSS. It also explores how some medications influence enzymes involved in epigenetic processes.
In the absence of a vaccine, the treatment of SARS-CoV2 has focused on eliminating the virus with antivirals or mitigating the cytokine storm syndrome (CSS) that leads to the most common cause of death: respiratory failure. Herein we discuss the mechanisms of antiviral treatments for SARS-CoV2 and treatment strategies for the CSS. Antivirals that have shown in vitro activity against SARS-CoV2, or the dosely related SARS-CoV1 and MERS-CoV, are compared on the enzymatic level and by potency in cells. For treatment of the CSS, we discuss medications that reduce the effects or expression of cytokines involved in the CSS with an emphasis on those that reduce IL-6 because of its central role in the development of the CSS. We show that some of the medications covered influence the activity or expression of enzymes involved in epigenetic processes and specifically those that add or remove modifications to histones or DNA. Where available, the latest clinical data showing the efficacy of the medications is presented. With respect to their mechanisms, we explain why some medications are successful, why others have failed, and why some untested medications may yet prove useful.

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