Abstract
Nonstructural protein 1 (nsp1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a 180-residue protein that blocks the translation of SARS-CoV-2 infected cells. Although it has been known that SARS-CoV-2’s own RNA evades an nsp1’s host translation shutoff, its molecular mechanism has been poorly understood. We performed an extended ensemble molecular dynamics simulation to investigate the mechanism of viral RNA evasion. Simulation results showed that the stem loop structure of SARS-CoV-2 RNA 5’-untranslated region is recognized by both nsp1’s globular region and intrinsically disordered region. The recognition presumably enables selectively translating the viral RNAs. A cluster analysis of the binding mode and a detailed analysis of the binding poses were performed, and we identified a few important residues involved in the SL1 recognition mechanism. The simulation results implied that nsp1 C-terminal helices are lifted from the 40S ribosome upon the binding of SL1 to the nsp1, reenabling the translation blocked by the C-terminal helices.
Competing Interest Statement
The authors have declared no competing interest.