Prunella vulgaris Extract Blocks SARS- Coronavirus 2 Virus Spike Protein D614 and G614 Variants Mediated Receptor Binding and Virus Entry

Until now, there is no approved effective vaccine, and antiviral therapeutic agents available for treatment or prevention of SARS-coronavirus 2 (SCoV-2) virus infection. In this study, we established a SCoV-2 Spike glycoprotein (SP) including an SP mutant D614G pseudotyped HIV-1-based vector system and tested their ability to infect ACE2-expressing cells. This study revealed that a C-terminal 17 amino acid deletion in SCoV-2 SP significantly increases the incorporation of SP into the pseudotyped viruses and enhanced its infectivity, which is valuable information for the design of SCoV2-SP-based vaccine strategies. Also, based on this system, we have demonstrated that an aqueous extract from the Chinese herb Prunella vulgaris (CHPV) displayed potent inhibitory effects on both SCoV-2 SP (including SPG614 mutant) pseudotyped virus (SCoV-2-SP-PVs) and SARS CoV SP-pseudotyped virus-mediated infections. Moreover, we have compared CHPV with another compound, Suramin, for their anti-SARS-CoV-2 activities and the mode of their actions, and found that both CHPV and Suramin are able to directly interrupt SCoV-2–SP binding to its receptor ACE2 and block the viral entry step. Importantly, our results also revealed that CHPV and Suramin were able to efficiently inhibit the wild type SARS-CoV-2 (hCoV-19/Canada/ON-VIDO-01/2020) virus infection in Vero cells. Furthermore, our results also demonstrated that the combination of CHPV/Suramin with an anti-SARS-CoV-2 neutralizing antibody mediated a more potent blocking effect against SCoV2-SP-PVs. Overall, this study provides pieces of strong evidence that CHPV and Suramin has anti-SARS-CoV-2 activity and may be developed as a novel antiviral approach, especially as nasopharynx agents, against SARS-CoV-2 infection.Funding: This work was supported by Canadian 2019 Novel Coronavirus (COVID-19) Rapid Research Funding (OV5-170710) by Canadian Institute of Health Research (CIHR) and Research Manitoba to X-J.Y and D.K.Conflict of Interest: The authors declare no competing interests.