PT - JOURNAL ARTICLE AU - Xiaoquan Li AU - Peter Lidsky AU - Yinghong Xiao AU - Chien-Ting Wu AU - Miguel Garcia-Knight AU - Junjiao Yang AU - Tsuguhisa Nakayama AU - Jayakar V. Nayak AU - Peter K. Jackson AU - Raul Andino AU - Xiaokun Shu TI - Ethacridine inhibits SARS-CoV-2 by inactivating viral particles in cellular models AID - 10.1101/2020.10.28.359042 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.10.28.359042 4099 - http://biorxiv.org/content/early/2020/11/02/2020.10.28.359042.short 4100 - http://biorxiv.org/content/early/2020/11/02/2020.10.28.359042.full AB - SARS-CoV-2 is the coronavirus that causes the respiratory disease COVID-19, which is now the third-leading cause of death in the United States. The FDA has recently approved remdesivir, an inhibitor of SARS-CoV-2 replication, to treat COVID-19, though recent data from the WHO shows little to no benefit with use of this anti-viral agent. Here we report the discovery of ethacridine, a safe antiseptic use in humans, as a potent drug for use against SARS-CoV-2 (EC50 ~ 0.08 μM). Ethacridine was identified via high-throughput screening of an FDA-approved drug library in living cells using a fluorescent assay. Interestingly, the main mode of action of ethacridine is through inactivation of viral particles, preventing their binding to the host cells. Indeed, ethacridine is effective in various cell types, including primary human nasal epithelial cells. Taken together, these data identify a promising, potent, and new use of the old drug possessing a distinct mode of action for inhibiting SARS-CoV-2.Competing Interest StatementWe have filed a patent on a new use of the identified compounds.