R-Propranolol Has Broad-Spectrum Anti-Coronavirus Activity and Suppresses Factors Involved in Pathogenic...

Area of Science:

• Virology
• Pharmacology
• Pathology

Background:

• The COVID-19 pandemic necessitates broad-spectrum antivirals effective beyond early infection stages.
• SARS-CoV-2 infection is linked to pathogenic angiogenesis in lungs, involving ANGPTL4 upregulation.
• Therapeutics should target viral replication and detrimental host responses like microvascular damage.

Purpose of the Study:

• To investigate the effects of propranolol on SARS-CoV-2 infection and ANGPTL4 expression.
• To evaluate R-propranolol, a propranolol enantiomer lacking beta-blocker activity, as a potential antiviral agent.

Main Methods:

• Assessed R-propranolol's impact on ANGPTL4 expression in SARS-CoV-2 infected cells.
• Measured SARS-CoV-2 replication inhibition in various cell lines and primary human airway epithelial cultures.
• Tested R-propranolol against SARS-CoV and MERS-CoV to determine spectrum of activity.

Main Results:

• SARS-CoV-2 infection upregulated ANGPTL4, which R-propranolol suppressed.
• R-propranolol inhibited SARS-CoV-2 replication by up to 2 logs across multiple cell types.
• R-propranolol demonstrated broad-spectrum antiviral activity against SARS-CoV and MERS-CoV, acting post-entry.

Conclusions:

• R-propranolol effectively inhibits SARS-CoV-2 replication and reduces viral load.
• The compound suppresses SARS-CoV-2-induced ANGPTL4 upregulation, potentially mitigating pathogenic angiogenesis.
• R-propranolol's broad-spectrum antiviral properties and host-response modulation make it a promising candidate for coronavirus treatment.