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....

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Bibliographic Details
Published in:bioRxiv 2021-06
Main Authors: Kilkenny, Mairi L, Veale, Charlotte E, Guppy, Amir, Hardwick, Steven W, Chirgadze, Dimitri Y, Rzechorzek, Neil J, Maman, Joseph D, Pellegrini, Luca
Format: Article
Language:English
Subjects:
Coronaviruses
COVID-19
Deoxyribonucleic acid
DNA
DNA biosynthesis
DNA primase
DNA viruses
DNA-directed DNA polymerase
Immune response
Infections
Molecular modelling
Pandemics
Primase
Protein interaction
Proteins
Severe acute respiratory syndrome coronavirus 2
Viral infections
Virulence
Virulence factors
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Summary: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. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2021.06.17.448816