Drugs that offer the potential to reduce hospitalization and mortality from SARS-CoV-2 infection: The possible role of the sigma-1 receptor and autophagy

James Michael Brimson; Mani Iyer Prasanth; Dicson Sheeja Malar; Sirikalaya Brimson; Premrutai Thitilertdecha; Tewin Tencomnao

doi:10.1080/14728222.2021.1952987

Drugs that offer the potential to reduce hospitalization and mortality from SARS-CoV-2 infection: The possible role of the sigma-1 receptor and autophagy

Expert Opin Ther Targets. 2021 Jun;25(6):435-449. doi: 10.1080/14728222.2021.1952987. Epub 2021 Jul 15.

Authors

James Michael Brimson^{1

2}, Mani Iyer Prasanth^{1

2}, Dicson Sheeja Malar^{1

2}, Sirikalaya Brimson³, Premrutai Thitilertdecha⁴, Tewin Tencomnao^{1

2}

Affiliations

¹ Natural Products for Neuroprotection and Anti-ageing Research Unit, Chulalongkorn University, Bangkok, Thailand.
² Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
³ Department of Clinical Microscopy, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
⁴ Siriraj Research Group in Immunobiology and Therapeutic Sciences, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Abstract

Introduction: Despite the availability of new vaccines for SARS-CoV-2, there has been slow uptake and problems with supply in some parts of the world. Hence, there is still a necessity for drugs that can prevent hospitalization of patients and reduce the strain on health care systems. Drugs with sigma affinity potentially provide protection against the most severe symptoms of SARS-COV-2 and could prevent mortality via interactions with the sigma-1 receptor.Areas covered: This review examines the role of the sigma-1 receptor and autophagy in SARS-CoV-2 infections and how they may be linked. The authors reveal how sigma ligands may reduce the symptoms, complications, and deaths resulting from SARS-CoV-2 and offer insights on those patient cohorts that may benefit most from these drugs.Expert opinion: Drugs with sigma affinity potentially offer protection against the most severe symptoms of SARS-CoV-2 via interactions with the sigma-1 receptor. Agonists of the sigma-1 receptor may provide protection of the mitochondria, activate mitophagy to remove damaged and leaking mitochondria, prevent ER stress, manage calcium ion transport, and induce autophagy to prevent cell death in response to infection.

Keywords: COVID-19; SARS-CoV-2; autophagy; chlorpromazine; critical care; donepezil; fluoxetine; fluvoxamine; long COVID; sigma-1.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Antiviral Agents / therapeutic use*
Autophagy*
COVID-19 / mortality
COVID-19 / virology
COVID-19 Drug Treatment*
Hospitalization / statistics & numerical data*
Humans
Receptors, sigma / physiology*
SARS-CoV-2 / isolation & purification
Sigma-1 Receptor

Substances

Antiviral Agents
Receptors, sigma

Grants and funding

J.M.B. and M.I.P. were funded by the Rachadapisek Sompote Fund for Postdoctoral Fellowship, Chulalongkorn University. D.S.M. was funded by The Second Century Fund (C2F) for Postdoctoral Fellowship, Chulalongkorn University.