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SARS-CoV-2 attenuates corticosteroid sensitivity by suppressing DUSP1 expression and activating p38 MAPK pathway
Fatemeh Saheb Sharif-Askari1, Narjes Saheb Sharif-Askari1, Swati Goel1
1Sharjah Institute of Medical Research, University of Sharjah, Sharjah, United Arab Emirates.
European Journal of Pharmacology
|July 25, 2021
Summary
SARS-CoV-2 infection lowers DUSP1, potentially causing steroid resistance by activating the MAPK pathway. Chloroquine may restore DUSP1, improving steroid treatment effectiveness for COVID-19.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- The use of corticosteroids for treating SARS-CoV-2 (COVID-19) infections remains controversial.
- Understanding the molecular mechanisms behind steroid resistance in COVID-19 is crucial for effective treatment strategies.
Purpose of the Study:
- To investigate the role of DUSP1 expression in SARS-CoV-2 infection.
- To explore the potential of chloroquine in modulating DUSP1 expression and the MAPK pathway for improved steroid sensitivity in COVID-19 treatment.
Main Methods:
- Analysis of SARS-CoV-2 infected lung tissue and nasopharyngeal swab data sets.
- In vitro experiments to assess DUSP1 expression and MAPK pathway activation.
- Evaluation of chloroquine's effect on DUSP1 and MAPK signaling.
Main Results:
- SARS-CoV-2 infection was found to significantly downregulate DUSP1 expression.
- Downregulation of DUSP1 is linked to enhanced MAPK pathway activation and steroid resistance in SARS-CoV-2 infection.
- Chloroquine demonstrated the ability to induce DUSP1 and attenuate the MAPK pathway.
Conclusions:
- SARS-CoV-2-induced DUSP1 downregulation may explain steroid resistance via MAPK pathway activation.
- Chloroquine shows potential in enhancing steroid treatment sensitivity for COVID-19 by modulating DUSP1 and MAPK signaling.
- Further research is needed to confirm the therapeutic efficacy of chloroquine in this context.
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