An overview of anti-SARS-CoV-2 and anti-inflammatory potential of baicalein and its metabolite baicalin: Insights into molecular mechanisms

The current Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is highly contagious infection that breaks the healthcare systems of several countries worldwide. Till to date, no effective antiviral drugs against COVID-19 infection have reached the market, and some repurposed drugs and vaccines are prescribed for the treatment and prevention of this disease. The currently prescribed COVID-19 vaccines are less effective against the newly emergent variants of concern of SARS-CoV-2 due to several mutations in viral spike protein and obviously there is an urgency to develop new antiviral drugs against this disease. In this review article, we systematically discussed the anti-SARS-CoV-2 and anti-inflammatory efficacy of two flavonoids, baicalein and its 7-O-glucuronide, baicalin, isolated from Scutellaria baicalensis, Oroxylum indicum, and other plants as well as their pharmacokinetics and oral bioavailability, for development of safe and effective drugs for COVID-19 treatment. Both baicalein and baicalin target the activities of viral S-, 3CL-, PL-, RdRp- and nsp13-proteins, and host mitochondrial OXPHOS for suppression of viral infection. Moreover, these compounds prevent sepsis-related inflammation and organ injury by modulation of host innate immune responses. Several nanoformulated and inclusion complexes of baicalein and baicalin have been reported to increase oral bioavailability, but their safety and efficacy in SARS-CoV-2-infected transgenic animals are not yet evaluated. Future studies on these compounds are required for use in clinical trials of COVID-19 patients.