RT Journal Article
SR Electronic
T1 Binding of SARS-CoV-2 non-structured protein 1 to 40S ribosome inhibits mRNA translation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.02.24.529933
DO 10.1101/2023.02.24.529933
A1 Hung Nguyen
A1 Hoang Linh Nguyen
A1 Mai Suan Li
YR 2023
UL http://biorxiv.org/content/early/2023/02/27/2023.02.24.529933.abstract
AB Experiments have shown that non-structural protein 1 (NSP1) of SARS-CoV-2 is a factor that restricts cellular gene expression and prevents mRNA translation in the ribosome 40S subunit. However, the molecular mechanism of this phenomenon remains unclear. To clarify this issue, all-atom steered molecular dynamics and coarse-grained alchemical simulations were used to compare the binding affinity of mRNA to 40S ribosome in the absence and presence of NSP1. We found that NSP1 binding to the 40S ribosome dramatically increases the binding affinity of mRNA, which, in agreement with experiment, suggests that NSP1 can stall mRNA translation. The mRNA translation has been found to be driven by electrostatic mRNA-40S ribosome interactions. Water molecules have been demonstrated to play an important role in stabilizing the mRNA-40S ribosome complex. The NSP1 residues that are critical in triggering a translation arrest have been identified.Competing Interest StatementThe authors have declared no competing interest.