COVID-19 has caused a severe global pandemic. Until now, there has been no simple and reliable system available in a lower-biosafety-grade laboratory for SARS-CoV-2 virologic research and inhibitor screening. ABSTRACT The etiologic agent of COVID-19 is highly contagious and has caused a severe global pandemic. Until now, there has been no simple and reliable system available in a lower-biosafety-grade laboratory for SARS-CoV-2 virologic research and inhibitor screening. In this study, we reported a replicon system which consists of four plasmids expressing the required segments of SARS-CoV-2. Our study revealed that the features for viral RNA synthesis and responses to antivirus drugs of the replicon are similar to those of wild-type viruses. Further analysis indicated that ORF6 provided potent in trans stimulation of the viral replication. Some viral variations, such as 5′UTR-C241T and ORF8-(T28144C) L84S mutation, also exhibit their different impact upon viral replication. Besides, the screening of clinically used drugs identified that several tyrosine kinase inhibitors and DNA-Top II inhibitors potently inhibit the replicon, as well as authentic SARS-CoV-2 viruses. Collectively, this replicon system provides a biosafety-worry-free platform for studying SARS-CoV-2 virology, monitoring the functional impact of viral mutations, and developing viral inhibitors.
【저자키워드】 COVID-19, SARS-CoV-2, safety replicon, 【초록키워드】 viruses, tyrosine kinase inhibitor, Mutation, drug, inhibitors, Laboratory, replicon, global pandemic, Viral, ORF8, viral replication, response, Research, kinase inhibitors, ORF6, Viral RNA, variations, inhibitor, Viral mutations, platform, Analysis, Plasmid, tyrosine, etiologic agent, tyrosine kinase inhibitors, SARS-CoV-2 viruses, viral RNA synthesis, wild-type, contagious, plasmids, antivirus drugs, feature, caused, reported, indicated, clinically, inhibit, required, provided, functional, provide, expressing, antivirus drug, 【제목키워드】 Screening, RNA, Viral, Engineering, synthesis, System,