SARS-CoV-2 attenuates corticosteroid sensitivity by suppressing DUSP1 expression and activating p38 MAPK pathway

Fatemeh Saheb Sharif-Askari; Narjes Saheb Sharif-Askari; Swati Goel; Shirin Hafezi; Rasha Assiri; Saleh Al-Muhsen; Qutayba Hamid; Rabih Halwani

doi:10.1016/j.ejphar.2021.174374

SARS-CoV-2 attenuates corticosteroid sensitivity by suppressing DUSP1 expression and activating p38 MAPK pathway

Eur J Pharmacol. 2021 Oct 5:908:174374. doi: 10.1016/j.ejphar.2021.174374. Epub 2021 Jul 22.

Authors

Fatemeh Saheb Sharif-Askari¹, Narjes Saheb Sharif-Askari¹, Swati Goel¹, Shirin Hafezi¹, Rasha Assiri², Saleh Al-Muhsen³, Qutayba Hamid⁴, Rabih Halwani⁵

Affiliations

¹ Sharjah Institute of Medical Research, University of Sharjah, Sharjah, United Arab Emirates.
² Department of Basic Science, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.
³ Immunology Research Lab, Department of Pediatrics, College of Medicine, King Saud University, Saudi Arabia; Department of Pediatrics, College of Medicine, King Saud University, Saudi Arabia.
⁴ Sharjah Institute of Medical Research, University of Sharjah, Sharjah, United Arab Emirates; Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; Meakins-Christie Laboratories, Research Institute of the McGill University Health Center, Montreal, Quebec, Canada.
⁵ Sharjah Institute of Medical Research, University of Sharjah, Sharjah, United Arab Emirates; Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; Prince Abdullah Ben Khaled Celiac Disease Chair, Department of Pediatrics, Faculty of Medicine, King Saud University, Saudi Arabia. Electronic address: rhalwani@sharjah.ac.ae.

Abstract

The efficacy of corticosteroids and its use for the treatment of SARS-CoV-2 infections is controversial. In this study, using data sets of SARS-CoV-2 infected lung tissues and nasopharyngeal swabs, as well as in vitro experiments, we show that SARS-CoV-2 infection significantly downregulates DUSP1 expression. This downregulation of DUSP1 could be the mechanism regulating the enhanced activation of MAPK pathway as well as the reported steroid resistance in SARS-CoV-2 infection. Moreover, chloroquine, an off labeled COVID-19 drug is able to induce DUSP1 and attenuate MAPK pathway; and is expected to improve sensitivity to steroid treatment. However, further mechanistic studies are required to confirm this effect.

Keywords: COVID-19; Chloroquine; Corticosteroid; DUSP1; SARS-CoV-2; p38 MAPK pathway.

Publication types

Observational Study

MeSH terms

Adult
Aged
COVID-19 / pathology
COVID-19 / virology
COVID-19 Drug Treatment*
Case-Control Studies
Cells, Cultured
Chloroquine / pharmacology*
Chloroquine / therapeutic use
Datasets as Topic
Down-Regulation / drug effects
Drug Resistance / drug effects
Drug Resistance / genetics
Drug Synergism
Dual Specificity Phosphatase 1 / genetics*
Dual Specificity Phosphatase 1 / metabolism
Fibroblasts
Glucocorticoids / pharmacology*
Glucocorticoids / therapeutic use
Healthy Volunteers
Humans
Lung / cytology
Lung / pathology
MAP Kinase Signaling System / drug effects
MAP Kinase Signaling System / genetics
Middle Aged
Nasopharynx / virology
Off-Label Use
Primary Cell Culture
SARS-CoV-2 / isolation & purification
SARS-CoV-2 / pathogenicity
p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

Glucocorticoids
Chloroquine
p38 Mitogen-Activated Protein Kinases
DUSP1 protein, human
Dual Specificity Phosphatase 1