PT  - JOURNAL ARTICLE
AU  - Hung Nguyen
AU  - Hoang Linh Nguyen
AU  - Mai Suan Li
TI  - Binding of SARS-CoV-2 non-structured protein 1 to 40S ribosome inhibits mRNA translation
AID  - 10.1101/2023.02.24.529933
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.02.24.529933
4099  - http://biorxiv.org/content/early/2023/02/27/2023.02.24.529933.short
4100  - http://biorxiv.org/content/early/2023/02/27/2023.02.24.529933.full
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.