The functional role of cyclophilins and the effect of cyclophilin inhibitors in coronavirus infection

本项目旨在研究亲环蛋白在病毒复制中的分子作用，开发体外阻断SARS-CoV2和其他人畜冠状病毒的亲环蛋白抑制剂。特别是，我们将研究(i) SARS-CoV2蛋白是否和亲环蛋白相互作用以及如何相互作用，（ii）这些相互作用对病毒复制以及先天和适应性免疫反应的影响，（iii）参与其中的分子机制和细胞途径，（iv）是否可以确定更有效的非免疫抑制性亲环蛋白抑制剂，以阻断SARS-CoV2、其他冠状病毒和其他病毒家族的成员。这个多学科项目涉及广泛的不同前沿分子、细胞、生化和生物物理技术，包括siRNA敲除、CRISPR基因编辑和SPR。

The aim of this project is to investigate the molecular role of cyclophilins in virus replication, to develop cyclophilin inhibitors that block SARS-CoV2 and other human and animal coronaviruses in vitro. In particular, we will investigate (i) whether and how SARS-CoV2 proteins interact with cyclophilins, (ii) the effect of these interactions on viral replication and the innate and adaptive immune response, (iii) the molecular mechanisms and cellular pathways involved in them, (iv) whether more potent, non-immunosuppressive cyclophilin inhibitors can be identified that block SARS-CoV2, other coronaviruses and members of other virus families. This multi-disciplinary project involves a broad range of different cutting-edge molecular, cellular, biochemical and biophysical technologies including for example siRNA knockdown, CRISPR gene editing and SPR.