PT - JOURNAL ARTICLE AU - Zhujun Ao AU - Mable Chan AU - Maggie Jing Ouyang AU - Olukitibi Titus Abiola AU - Mona Mahmoudi AU - Darwyn Kobasa AU - Xiaojian Yao TI - <em>Prunella vulgaris</em> extract and suramin block SARS-coronavirus <em>2</em> virus Spike protein D614 and G614 variants mediated receptor association and virus entry in cell culture system AID - 10.1101/2020.08.28.270306 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.08.28.270306 4099 - http://biorxiv.org/content/early/2020/08/28/2020.08.28.270306.short 4100 - http://biorxiv.org/content/early/2020/08/28/2020.08.28.270306.full AB - Until now, no approved effective vaccine and antiviral therapeutic are 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 a 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 may be helpful in the design of SCoV2-SP-based vaccine strategies. Moreover, based on this system, we have demonstrated that an aqueous extract from the Chinese herb Prunella vulgaris (CHPV) and a compound, suramin, displayed potent inhibitory effects on both wild type and mutant (G614) SCoV-2 SP pseudotyped virus (SCoV-2-SP-PVs)-mediated infection. The 50% inhibitory concentration (IC50) for CHPV and suramin on SCoV-2-SP-PVs are 30, and 40 μg/ml, respectively. To define the mechanisms of their actions, we demonstrated 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 showed that CHPV or suramin can efficiently reduce levels of cytopathic effect caused by SARS-CoV-2 virus (hCoV-19/Canada/ON-VIDO-01/2020) infection in Vero cells. Furthermore, our results demonstrated that the combination of CHPV/suramin with an anti-SARS-CoV-2 neutralizing antibody mediated more potent blocking effect against SCoV2-SP-PVs. Overall, this study provides evidence that CHPV and suramin has anti-SARS-CoV-2 activity and may be developed as a novel antiviral approach against SARS-CoV-2 infection.Competing Interest StatementThe authors have declared no competing interest.