Unraveling the Role of Nsp1 in SARS-CoV-2: Mechanisms of mRNA Degradation and Viral Proliferation

Abstract

Coronaviruses produce Nsp1 as their first viral protein upon infecting host cells. Nsp1 inhibits the production of host proteins and causes degradation of host mRNA to support viral growth. However, the exact process by which Nsp1 induces cellular mRNA degradation is not fully understood.

In this study, we investigate how Nsp1 affects host mRNA stability using cell-free translation methods. Our findings show that the binding of SARS-CoV-2 Nsp1 to the ribosome is sufficient to initiate mRNA degradation. This process occurs without ribosome collisions or active translation. In contrast, MERS-CoV Nsp1 inhibits translation but does not induce degradation, indicating different mechanisms of action for these two proteins.

Additionally, Nsp1 and viral mRNAs have evolved together, which protects viral mRNAs from degradation by Nsp1 in SARS-CoV-2, MERS-CoV, and Bat-Hp viruses. These insights enhance our understanding of Nsp1’s function and could aid in developing new treatments for coronaviral infections.