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10.1099/jgv.0.001513

http://scihub22266oqcxt.onion/10.1099/jgv.0.001513
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33151142!8116783!33151142
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suck abstract from ncbi


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pmid33151142      J+Gen+Virol 2021 ; 102 (1): ä
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  • Lysine 164 is critical for SARS-CoV-2 Nsp1 inhibition of host gene expression #MMPMID33151142
  • Shen Z; Zhang G; Yang Y; Li M; Yang S; Peng G
  • J Gen Virol 2021[Jan]; 102 (1): ä PMID33151142show ga
  • The emerging pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused social and economic disruption worldwide, infecting over 9.0 million people and killing over 469 000 by 24 June 2020. Unfortunately, no vaccine or antiviral drug that completely eliminates the transmissible disease coronavirus disease 2019 (COVID-19) has been developed to date. Given that coronavirus nonstructural protein 1 (nsp1) is a good target for attenuated vaccines, it is of great significance to explore the detailed characteristics of SARS-CoV-2 nsp1. Here, we first confirmed that SARS-CoV-2 nsp1 had a conserved function similar to that of SARS-CoV nsp1 in inhibiting host-protein synthesis and showed greater inhibition efficiency, as revealed by ribopuromycylation and Renilla luciferase (Rluc) reporter assays. Specifically, bioinformatics and biochemical experiments showed that by interacting with 40S ribosomal subunit, the lysine located at amino acid 164 (K164) was the key residue that enabled SARS-CoV-2 nsp1 to suppress host gene expression. Furthermore, as an inhibitor of host-protein expression, SARS-CoV-2 nsp1 contributed to cell-cycle arrest in G0/G1 phase, which might provide a favourable environment for virus production. Taken together, this research uncovered the detailed mechanism by which SARS-CoV-2 nsp1 K164 inhibited host gene expression, laying the foundation for the development of attenuated vaccines based on nsp1 modification.
  • |Amino Acid Sequence[MESH]
  • |Amino Acid Substitution[MESH]
  • |Computational Biology/methods[MESH]
  • |G1 Phase Cell Cycle Checkpoints/genetics[MESH]
  • |Gene Expression Regulation[MESH]
  • |Genes, Reporter[MESH]
  • |HEK293 Cells[MESH]
  • |Host-Pathogen Interactions/*genetics[MESH]
  • |Humans[MESH]
  • |Luciferases/genetics/metabolism[MESH]
  • |Lysine/*genetics/metabolism[MESH]
  • |Mutation[MESH]
  • |Ribosomal Proteins/antagonists & inhibitors/*genetics/metabolism[MESH]
  • |Ribosome Subunits, Small, Eukaryotic/*genetics/metabolism/virology[MESH]
  • |SARS-CoV-2/*genetics/metabolism[MESH]
  • |Sequence Alignment[MESH]
  • |Sequence Homology, Amino Acid[MESH]
  • |Severe acute respiratory syndrome-related coronavirus/genetics/metabolism[MESH]
  • |Signal Transduction[MESH]


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