Structural basis for the interaction of SARS-CoV-2 virulence factor nsp1 with Pol α - Primase

The molecular mechanisms that drive the infection by the SARS-CoV-2 coronavirus – the causative agent of the COVID-19 (Coronavirus disease-2019) pandemic – are under intense current scrutiny, to understand how the virus operates and to uncover ways in which the disease can be prevented or alleviated.

Recent cell-based analyses of SARS-CoV-2 protein - protein interactions have mapped the human proteins targeted by the virus. The DNA polymerase α - primase complex or primosome – responsible for initiating DNA synthesis in genomic duplication – was identified as a target of nsp1 (non structural protein 1), a major virulence factor in the SARS-CoV-2 infection.

Here, we report the biochemical characterisation of the interaction between nsp1 and the primosome and the cryoEM structure of the primosome - nsp1 complex. Our data provide a structural basis for the reported interaction between the primosome and nsp1. They suggest that Pol α - primase plays a part in the immune response to the viral infection, and that its targeting by SARS-CoV-2 aims to interfere with such function.