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Based on our high-throughput screening assay using a compound library, we identified seven compounds with broad-spectrum efficacy against the replication of four CoVs\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Additionally, one compound (lycorine) was found to protect BALB\/c mice against HCoV-OC43-induced lethality by decreasing viral load in the central nervous system. 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