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The emergence and re-emergence of coronaviruses (CoV) continually cause circulating epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. The resultant disease, coronavirus disease 2019 (COVID-19), has rapidly developed into a worldwide pandemic, leading to severe health and economic burdens. Although the recently announced vaccines against COVID-19 has rekindled hope, there is still a major challenge to urgently meet the global need for rapid treatment of the pandemic. Given the urgency of the CoV outbreak, we propose a strategy to screen potential broad-spectrum drugs against CoV in a high-throughput manner, particularly against SARS-CoV-2. Since the essential functional domains of CoV are extensively homologous, the availability of two types of mild CoV, HCoV-OC43 and MHV, should provide a valuable tool for the rapid identification of promising drugs against CoV without the drawbacks of level three biological confinements. The luciferase reporter gene is introduced into HCoV-OC43 and MHV to indicate viral activity, and hence the antiviral efficiency of screened drugs can be quantified by luciferase activity. Compounds with antiviral activity against both HCoV-OC43 and MHV are further evaluated in SARS-CoV-2 after structural optimizations. This system allows large-scale compounds to be screened to search for broad-spectrum drugs against CoV in a high-throughput manner, providing potential alternatives for clinical management of SARS-CoV-2 or other CoV.
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10.1016/j.ijid.2020.12.033
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document_parses/pdf_json/82d8eb87b9f17e2643c02ad4d23b58389a47611f.json
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document_parses/pmc_json/PMC7832824.xml.json
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A high-throughput drug screening strategy against coronaviruses
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