mTOR inhibition in COVID-19: A commentary and review of efficacy in RNA viruses

Affiliations

¹ Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
² Division of General Internal Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
³ Department of Emergency Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
⁴ University of Minnesota Medical School, Minneapolis, Minnesota, USA.
⁵ Division of Rheumatology, Department of Medicine, Minneapolis, Minnesota, USA.
⁶ Division of Pulmonary and Critical Care, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
⁷ Department of Surgery, University of North Carolina, Chapel Hill, North Carolina, USA.
⁸ School of Public Health, University of North Carolina, Chapel Hill, North Carolina, USA.
⁹ Department of Biomedical Engineering, University of Minnesota, Minnesota, USA.
¹⁰ Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
¹¹ Institute for Health Informatics, University of Minnesota, Minneapolis, Minnesota, USA.

PMID: 33314219
PMCID: PMC8159020
DOI: 10.1002/jmv.26728

Review

mTOR inhibition in COVID-19: A commentary and review of efficacy in RNA viruses

Basil S Karam et al. J Med Virol. 2021 Apr.

. 2021 Apr;93(4):1843-1846.

doi: 10.1002/jmv.26728. Epub 2020 Dec 17.

Authors

Affiliations

¹ Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
² Division of General Internal Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
³ Department of Emergency Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
⁴ University of Minnesota Medical School, Minneapolis, Minnesota, USA.
⁵ Division of Rheumatology, Department of Medicine, Minneapolis, Minnesota, USA.
⁶ Division of Pulmonary and Critical Care, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
⁷ Department of Surgery, University of North Carolina, Chapel Hill, North Carolina, USA.
⁸ School of Public Health, University of North Carolina, Chapel Hill, North Carolina, USA.
⁹ Department of Biomedical Engineering, University of Minnesota, Minnesota, USA.
¹⁰ Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
¹¹ Institute for Health Informatics, University of Minnesota, Minneapolis, Minnesota, USA.

PMID: 33314219
PMCID: PMC8159020
DOI: 10.1002/jmv.26728

Abstract

In this commentary, we shed light on the role of the mammalian target of rapamycin (mTOR) pathway in viral infections. The mTOR pathway has been demonstrated to be modulated in numerous RNA viruses. Frequently, inhibiting mTOR results in suppression of virus growth and replication. Recent evidence points towards modulation of mTOR in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We discuss the current literature on mTOR in SARS-CoV-2 and highlight evidence in support of a role for mTOR inhibitors in the treatment of coronavirus disease 2019.

Keywords: COVID-19; mTOR; mTORi.

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Conflict of interest statement

CONFLICT OF INTERESTS

Christopher J. Tignanelli and Michael Puskarich are investigators on two randomized controlledtrials of Losartan in COVID-19. All remaining authors have no potential conflicts to declare.

Figures

**FIGURE 1**
Inhibition of mTORC1 by mTOR inhibitors may promote autophagy of infected cells and inhibit translation of SARS-CoV-2 viral polymerase and structural proteins. mTOR, mammalian target of rapamycin; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2

See this image and copyright information in PMC

References

1. Ingraham NE, Barakat AG, Reilkoff R, et al. Understanding the reninangiotensin-aldosterone-SARS-CoV axis: a comprehensive review. Eur Respir J. 2020;56(1):2000912. - PMC - PubMed
1. Ingraham NE, Lotfi-Emran S, Thielen BK, et al. Immunomodulation in COVID-19. Lancet Respir Med. 2020;8(6):544–546. - PMC - PubMed
1. Le Sage V, Cinti A, Amorim R, Mouland AJ. Adapting the stress response: viral subversion of the mTOR signaling pathway. Viruses. 2016;8(6):152. - PMC - PubMed
1. Terrazzano G, Rubino V, Palatucci AT, Giovazzino A, Carriero F, Ruggiero G. An open question: is it rational to inhibit the mTor-dependent pathway as COVID-19 therapy? Front Pharmacol. 2020;11:856. - PMC - PubMed
1. Castle BT, Dock C, Hemmat M, et al. Biophysical modeling of the SARS-CoV-2 viral cycle reveals ideal antiviral targets. Biorxiv. 2020.

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mTOR inhibition in COVID-19: A commentary and review of efficacy in RNA viruses

Affiliations

mTOR inhibition in COVID-19: A commentary and review of efficacy in RNA viruses

Authors

Affiliations

Abstract

Conflict of interest statement

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