Modelling the Active SARS-CoV-2 Helicase Complex as a Basis for Structurebased Inhibitor Design

Dénes Berta, Magd Badaoui, Sam Alexander Martino, Pedro J. Buigues, Andrei V. Pisliakov, Nadia Elghobashi-Meinhardt, Geoff Wells, Sarah A. Harris, Elisa Frezza, Edina Rosta

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
50 Downloads (Pure)


The RNA helicase (non-structural protein 13, NSP13) of SARS-CoV-2 is essential for viral replication, and it is highly conserved among the coronaviridae family, thus a prominent drug target to treat COVID-19. We present here structural models and dynamics of the helicase in complex with its native substrates based on thorough analysis of homologous sequences and existing experimental structures. We performed and analysed microseconds of molecular dynamics (MD) simulations, and our model provides valuable insights to the binding of the ATP and ssRNA at the atomic level. We identify the principal motions characterising the enzyme and highlight the effect of the natural substrates on this dynamics. Furthermore, allosteric binding sites are suggested by our pocket analysis. Our obtained structural and dynamical insights are important for subsequent studies of the catalytic function and for the development of specific inhibitors at our characterised binding pockets for this promising COVID-19 drug target.
Original languageEnglish
Pages (from-to)13492-13505
Number of pages14
JournalChemical Science
Issue number40
Early online date6 Sept 2021
Publication statusPublished - 28 Oct 2021

ASJC Scopus subject areas

  • General Chemistry


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