TY - JOUR
AU - Berta, Dénes
AU - Badaoui, Magd
AU - Martino, Sam Alexander
AU - Buigues, Pedro J.
AU - Pisliakov, Andrei V.
AU - Elghobashi-Meinhardt, Nadia
AU - Wells, Geoff
AU - Harris, Sarah A.
AU - Frezza, Elisa
AU - Rosta, Edina
PY - 2021
DA - October
TI - Modelling the Active SARS-CoV-2 Helicase Complex as a Basis for Structure-based Inhibitor Design
JO - Chemical Science
EP - 13505
VL - 12
IS - 40
DO - https://doi.org/10.1039/D1SC02775A
AB - 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.
PB - Royal Society of Chemistry
UR - https://discovery.dundee.ac.uk/en/publications/baefeed5-8df5-474b-85f5-7afbc30a1e9d
KW - Coronavirus (COVID-19)
ER