Abstract 1158 Exploring the functions of SARS coronavirus nonstructural protein 1 in differentiating viral RNA and host mRNA

Nonstructural protein 1 (nsp1) of recent zoonotic coronaviruses (SARS-CoV-1, SARS-CoV-2, MERS-CoV) acts as the host shutoff protein that stalls host mRNA translation and triggers their degradation, successfully suppressing host gene expression. In contrast, viral RNA selectively escapes the effects of the two-pronged suppression mechanism and continues the synthesis of viral proteins due to the presence of stem-loop 1 (SL1) in the viral leader sequence. Recent structure analysis of nsp1 bound to the 40S ribosomal subunit suggests that the flexible C-terminal region of nsp1 binds to the 40S ribosome at the mRNA binding site by folding into two defined structures (alpha-helices); this interaction blocks host mRNAs from binding, stalling host mRNA translation.