Scutellaria barbata D. Don extracts alleviate SARS-CoV-2 induced acute lung injury by inhibiting virus replication and bi-directional immune modulation.

The emergence of SARS-CoV-2 variants and drug-resistant mutants emphasizes the urgent need to develop novel antiviral agents. In the present study, we examined the therapeutic effect of the Chinese medicinal herb, Scutellaria barbata D. Don (SBD), against SARS-CoV-2 infection both in vitro and in vivo. Using a viral replicon particle (VRP)-based mouse model of SARS-CoV-2 infection, our study revealed that SBD extracts can reduce viral load in mouse lungs and alleviate the viral induced pneumonia. In vitro antiviral determination further validated the direct acting antiviral efficacy of SBD extracts against SARS-CoV-2 replication. Mechanistic studies demonstrated that SBD can act against SARS-CoV-2 replication by targeting both 3-chymotrypsin-like and papain-like cysteine proteases, via a combination of multiple active constituents. Moreover, SBD can modulate the host inflammation response in a bi-directional manner, which also contribute to the mitigation of viral induced acute lung injury. In summary, our study provides SBD as a promising therapeutic agent to combat SARS-CoV-2 infections that merit further development.