Ethacridine Inhibits Sars-Cov-2 By Inactivating Viral Particles

Author summary To identify inhibitors against SARS-CoV-2, here we have designed and demonstrated a high throughput screening system that works in living cells at BSL2. To repurpose existing drugs, we have screened an FDA-approved drug library and identified several drugs that inhibit Mpro and block SARS-CoV-2 in cells. Interestingly, one of the identified drugs, ethacridine, shows ~40-fold higher antiviral activity than its antiprotease activity. Further studies unveil that ethacridine inhibits the coronavirus by inactivating the viral particles. Our work demonstrated a powerful tool to screen protease inhibitors to inhibit coronavirus, as well as other diseases in the future.The respiratory disease COVID-19 is caused by the coronavirus SARS-CoV-2. Here we report the discovery of ethacridine as a potent drug against SARS-CoV-2 (EC50 ~ 0.08 mu M). Ethacridine was identified via high-throughput screening of an FDA-approved drug library in living cells using a fluorescence assay. Plaque assays, RT-PCR and immunofluorescence imaging at various stages of viral infection demonstrate that the main mode of action of ethacridine is through inactivation of viral particles, preventing their binding to the host cells. Consistently, ethacridine is effective in various cell types, including primary human nasal epithelial cells that are cultured in an air-liquid interface. Taken together, our work identifies a promising, potent, and new use of the old drug via a distinct mode of action for inhibiting SARS-CoV-2.