Daphnetin may protect from SARS-CoV-2 infection by reducing ACE2

Area of Science:

• Pharmacology
• Virology
• Respiratory Medicine

Background:

• The SARS-CoV-2 pandemic necessitates novel prevention strategies.
• Reducing Angiotensin-Converting Enzyme 2 (ACE2) expression on respiratory cells is a potential intervention.
• Screening approved drugs for ACE2 downregulation is crucial.

Purpose of the Study:

• To identify existing drugs capable of reducing ACE2 expression.
• To evaluate the efficacy of Daphnetin (DAP) in downregulating ACE2.
• To assess DAP's potential as a preventive measure against SARS-CoV-2.

Main Methods:

• Drug screening of approved medications in China.
• Quantitative analysis of ACE2 mRNA and protein levels in PC9 cells.
• SARS-CoV-2 pseudovirus infection assays.
• In vivo studies in mice and human respiratory systems.

Main Results:

• Daphnetin (DAP) significantly reduced ACE2 mRNA and protein levels in PC9 cells.
• DAP targets HIF-1α and JAK2, inhibiting ACE2 gene transcription.
• DAP-treated cells showed reduced susceptibility to SARS-CoV-2 pseudovirus infection.
• Therapeutic doses of DAP lowered ACE2 expression in mouse and human respiratory systems.

Conclusions:

• Daphnetin (DAP) effectively downregulates ACE2 expression.
• DAP demonstrates potential as a preventive agent against SARS-CoV-2 infection.
• DAP offers a cost-effective and accessible strategy to mitigate SARS-CoV-2 spread.