TY - JOUR T1 - Screening of Botanical Drugs against SARS-CoV-2 Entry JF - bioRxiv DO - 10.1101/2021.06.03.447021 SP - 2021.06.03.447021 AU - Junyuan Cao AU - Yang Liu AU - Minmin Zhou AU - Siqi Dong AU - Xiaoying Jia AU - Xiaohao Lan AU - Yueli Zhang AU - Jiao Guo AU - Gengfu Xiao AU - Wei Wang Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/06/04/2021.06.03.447021.abstract N2 - An escalating pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is impacting global health. Specific treatment options for diseases caused by SARS-CoV-2 are largely lacking. Herein, we used a pseudotype virus (pv) bearing the SARS-CoV-2 S glycoprotein to screen a botanical drug library to identify an agent against SARS-CoV-2 entry. All the four hits, including angeloylgomisin O, schisandrin B, procyanidin, and oleanonic acid, were identified for effective inhibition of SARS-CoV-2 S pv entry in the micromolar range. A mechanistic study revealed that these four agents inhibit SARS-CoV-2 S pv entry by blocking S-mediated membrane fusion. Furthermore, angeloylgomisin O, schisandrin B, and oleanonic acid inhibited authentic SARS-CoV-2 with a high selective index (SI). We also showed that all the four hits could also inhibit the entry of pv of Middle East respiratory syndrome coronavirus (MERS-CoV) and newly emerged SARS-CoV-2 variants (D614G, K417N/E484K/N501Y/D614G). In drug combination studies performed in cellular antiviral assays, angeloylgomisin O and schisandrin B displayed synergistic effects in combination with remdesivir. These results indicated that angeloylgomisin O, schisandrin B, procyanidin, and oleanonic acid can inhibit SARS-CoV-2 and that they are potential therapeutic agents for COVID-19. ER -