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bioRxiv · 10.1101/2021.06.17.448816

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

Kilkenny, M. L.·Veale, C. E.·Guppy, A.·Hardwick, S. W.·Chirgadze, D. Y.·Rzechorzek, N. J.·Maman, J. D.·Pellegrini, L.
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Abstract

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 - 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 - 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.

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Kilkenny, M. L., Veale, C. E., Guppy, A., Hardwick, S. W., Chirgadze, D. Y., Rzechorzek, N. J., Maman, J. D., Pellegrini, L.. 2021-06-19. Structural basis for the interaction of SARS-CoV-2 virulence factor nsp1 with Pol α - Primase. https://doi.org/10.1101/2021.06.17.448816

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