DNA损伤应答关键蛋白在冠状病毒复制中的作用及机制

目前冠状病毒的感染复制机制尚未完全阐明。DNA损伤应答（DDR）是细胞维持基因组稳定性的重要途径，其在冠状病毒复制中的功能未见报道。近期的研究发现新型冠状病毒SARS-CoV-2与BRCA2等DDR关键蛋白存在相互作用，而我们的初步结果表明BRCA2的缺失会导致SARS-CoV-2复制水平下降，提示BRCA2很可能参与SARS-CoV-2的复制过程。本研究拟在此基础上，以人冠状病毒SARS-CoV-2和HCoV-OC43为模型，进一步筛选其他参与冠状病毒复制的DDR关键蛋白，探究这些蛋白参与冠状病毒复制的分子机制，并从感染角度出发，研究冠状病毒感染对宿主细胞基因组及DDR的影响。因此，本研究将从DDR这一新角度深入探究冠状病毒感染复制机制，阐明DDR关键蛋白调控冠状病毒复制的分子机制，为抗病毒治疗药物提供新的靶标。

To date, the mechanisms of infection and replication of coronavirus have not been fully elucidated. The functions of host factors in infection and replication of coronavirus need to be further studied. DNA damage response (DDR) is a mechanism by which cells maintain genome stability, the role of DDR in replication of coronavirus remains unclear. Recent interactome studies found that some of the key proteins of DDR, including BRCA2, interact with the newly identified coronavirus SARS-CoV-2. Our preliminary data also showed that depletion of BRCA2 reduced the RNA and protein level of SARS-CoV-2 in A549-ACE2 cells upon infection, suggesting that BRCA2 is needed in replication of SARS-CoV-2. Based on these findings, we will continue screening the key DDR factors that participate in replication of both SARS-CoV-2 and HCoV-OC43, study the mechanism of these factors in replication of coronavirus, and explore the impact of coronavirus infection on DDR and genome. This project will study the mechanism of replication of coronavirus with a new perspective, elucidate the role and mechanism of key DDR proteins in replication of coronavirus, and provide new target for antivirals.