An escalating pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has severely impacted global health. There is a severe lack of specific treatment options for diseases caused by SARS-CoV-2. In this study, we used a pseudotype virus (pv) containing the SARS-CoV-2 S glycoprotein to screen a botanical drug library containing 1037 botanical drugs to identify agents that prevent SARS-CoV-2 entry into the cell. Our study identified four hits, including angeloylgomisin O, schisandrin B, procyanidin, and oleanonic acid, as effective SARS-CoV-2 S pv entry inhibitors in the micromolar range. A mechanistic study revealed that these four agents inhibited SARS-CoV-2 S pv entry by blocking spike (S) protein-mediated membrane fusion. Furthermore, angeloylgomisin O and schisandrin B inhibited authentic SARS-CoV-2 with a high selective index (SI; 50% cytotoxic concentration/50% inhibition concentration). Our drug combination studies performed in cellular antiviral assays revealed that angeloylgomisin O has synergistic effects in combination with remdesivir, a drug widely used to treat SARS-CoV-2-mediated infections. We also showed that two hits could inhibit the newly emerged alpha (B.1.1.7) and beta (B.1.351) variants. Our findings collectively indicate that angeloylgomisin O and schisandrin B could inhibit SARS-CoV-2 efficiently, thereby making them potential therapeutic agents to treat the coronavirus disease of 2019.
【저자키워드】 SARS-CoV-2, combination therapy, Entry inhibitor, angeloylgomisin O, schisandrin B, 【초록키워드】 coronavirus disease, coronavirus, pandemic, B.1.351, Remdesivir, drug, variants, Health, infections, B.1.1.7, Alpha, membrane fusion, disease, S glycoprotein, cellular, antiviral assay, Combination, Concentration, acute respiratory syndrome, SARS-CoV-2 entry, drug combination, treat, SARS-CoV-2 S, specific treatment, selective, drug library, pseudotype virus, Effect, Prevent, effective, Cell, synergistic, identify, performed, lack, caused, inhibit, inhibited, potential therapeutic agent, impacted, inhibit SARS-CoV-2, the SARS-CoV-2, 【제목키워드】 COVID-19, drug, Screening, novel, agent,