The Swiss army knife of SARS-CoV-2: the structures and functions of NSP3

With up to 17 domains, non-structural protein 3 (nsp3) is the largest protein of SARS-CoV-2. In part due to its large size, many of its functions still remain a mystery. It is known that nsp3 fulfils several essential functions in the cycle of infection, however most of its domains have not been structurally determined. One of its essential functions is to cleave the polyprotein, which is translated first upon infection, into other functional non-structural proteins. Nsp3 is also involved in the evasion of the host immune system and forms large pore complexes important for viral replication. Furthermore, it interacts with more than 30 other host and viral proteins, resulting in a multitude of potential ways to affect the host cell and viral replication. The many roles of this coronaviral Swiss army knife make it a promising drug target. In this review, we aim to clarify naming conventions and give an overview on the structures and functions of its domains as a starting point for further research.