Nsp1

(pmid: 33188728) Nsp1 targets the 40S ribosomal subunit to stall the translation in multiple steps during initiation of translation and also induces an endonucleolytic cleavage of host RNA to accelerate degradation (Kamitani et al., 2009; Lokugamage et al., 2012). Nsp1 therefore has profound inhibitory effects on the host protein production, including suppressing the innate immune system to facilitate the viral replication (Narayanan et al., 2008) and potentially long-term cell viability consequences.

(pmid: 32638509) Nsp1: endoribonuclease activity that selectively targets cellular mRNAs fordegradation (Kamitani et al., 2006; Tohya et al., 2009). The massive degradation of cellular mRNAs enhances the forma-tion of stress granules and P bodies (retaining sites for downregulated mRNAs) during the infection (Raabenet al., 2007). SARS-CoV and MERS-CoV nsp1 associate with the stem loop (SL) SL1 hairpin in the 50UTR of corona viral mRNAs. The presence of the SL1 element in the 50UTR of viral mRNAs helps to protect these transcripts from nsp1-directed cleavage (Huang et al., 2011; Tanaka, Kamitani, DeDiego, Enjuanes, & Matsuura, 2012; Terada, Kawachi,Matsuura, & Kamitani, 2017). Curiously, the SARS-CoV nsp1 is a 179 amino acid protein with an irregular beta-barrelfold and lacks an obvious signature of a ribonuclease domain (Almeida, Johnson, Herrmann, Geralt, &Wüthrich, 2007). There is circumstantial evidence that the nsp1 protein coordinates its endonuclease activity with otheraspects of RNA biology in the cell. While the SARS-CoV nsp1 interfaces with translation via an interaction with the 40Sribosome, the MERS-CoV nsp1 protein instead shuttles between the nucleus and cytoplasm and selectively targetsmRNAs with a nuclear experience (i.e., all cellular mRNAs) for cleavage (Huang et al., 2011). Mutational analyses indi-cate that nsp1 and its endoribonucleolytic activity play an important role in dampening the innate immune response ofthe cell to viral infection (Narayanan et al., 2008). A recent study also associates the endoribonuclease activity with effi-cient coronaviral virion assembly or budding (Nakagawa et al., 2018). Therefore, this novel viral ribonuclease is clearly a major player in viral infections.