In vitro analyses have found that SARS-COV-1 nsp1 may disrupt the host interferon defense response, by potentially affecting the downstream defense signaling. The nsp1 protein has been shown to bind the 40S Ribosomal subunit, which has been associated with degradation of host mRNA, and suppression of host mRNA translation, leaving the viral RNA unaffected. SARS-CoV- 1 vs SARS-CoV-2: Variations in Loop 3-4 may influence the ability of SARS-CoV-2 nsp1 to disrupt host-translational activity.
The nonstructural protein 1 (nsp1) is the first nonstructural protein in the ORF1a/ORF1ab gene. Nsp1 is found within α and β coronaviruses. Experiments in vitro suggest that SARS-CoV-1 nsp1 disrupts the host interferon defense response by potentially affecting the downstream defense signaling (Krishna Narayanan et al. 2015, 2008; Züst et al. 2007). The nsp1 protein binds the 40S Ribosomal subunit, which has been associated with degradation of host mRNA and suppression of host mRNA translation, leaving the viral RNA unaffected (Züst et al. 2007; Kamitani et al. 2009). The resultant complex cleaves the 5′ UTR of host mRNAs, inhibiting translation. Substitutions in the loop 3-4 may impact host-translational activity (manuscript in review)