Are losartan and imatinib effective against SARS-CoV2 pathogenesis? A pathophysiologic-based in silico study

Area of Science:

• Pathophysiology
• Pharmacology
• In Silico Drug Discovery

Background:

• COVID-19-induced ARDS is linked to cytokine storm.
• ACE2 downregulation by SARS-CoV-2 may cause angiotensin II (AngII) upregulation, triggering ARDS.
• The role of angiotensin II type 1 receptor (AT1R) overactivation in ARDS requires further investigation.

Purpose of the Study:

• To propose a theory on COVID-19 cytokine storm pathophysiology.
• To identify potential drugs for treating COVID-19.
• To investigate the effects of losartan and imatinib on SARS-CoV-2 infectivity using in silico methods.

Main Methods:

• Literature review on AT1R activation in ARDS.
• In silico study to evaluate the effects of losartan and imatinib on SARS-CoV-2.
• Analysis of the renin-angiotensin system's role in COVID-19 pathophysiology.

Main Results:

• Overactivation of AT1R by AngII excess, due to ACE2 downregulation, precisely explains COVID-19 cytokine storm.
• In silico analysis suggests losartan and imatinib can decrease SARS-CoV-2 affinity to ACE2.
• Losartan and imatinib may inhibit key viral enzymes (main protease, furin) and host factors (papain-like protease, p38MAPK).

Conclusions:

• The proposed theory on AngII-induced cytokine storm in COVID-19-associated ARDS is supported by literature.
• Losartan and imatinib demonstrate potential therapeutic benefits against SARS-CoV-2 pathogenesis.
• These drugs may attenuate COVID-19 severity by modulating inflammatory responses and viral replication.