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Lysine 164 is critical for SARS-CoV-2 Nsp1 inhibition of host gene expression.
Shen, Zhou; Zhang, Guangxu; Yang, Yilin; Li, Mengxia; Yang, Siqi; Peng, Guiqing.
  • Shen Z; State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, PR China.
  • Zhang G; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, PR China.
  • Yang Y; State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, PR China.
  • Li M; State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, PR China.
  • Yang S; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, PR China.
  • Peng G; State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, PR China.
J Gen Virol ; 102(1)2021 01.
Article in English | MEDLINE | ID: covidwho-910383
Semantic information from SemMedBD (by NLM)
1. Antiviral Agents TREATS COVID-19
Subject
Antiviral Agents
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TREATS
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COVID-19
2. Vaccines TREATS COVID-19
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Vaccines
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TREATS
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COVID-19
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Assay
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USES
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Tracer
4. Synapsin I AFFECTS Cell Cycle Arrest
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Synapsin I
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AFFECTS
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Cell Cycle Arrest
5. Cell Cycle Arrest COEXISTS_WITH Resting Phas
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Cell Cycle Arrest
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COEXISTS_WITH
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Resting Phas
6. Antiviral Agents TREATS COVID-19
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Antiviral Agents
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TREATS
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COVID-19
7. Vaccines TREATS COVID-19
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Vaccines
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TREATS
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COVID-19
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USES
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9. Synapsin I AFFECTS Cell Cycle Arrest
Subject
Synapsin I
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AFFECTS
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Cell Cycle Arrest
10. Cell Cycle Arrest COEXISTS_WITH Resting Phase, Cell Cycle
Subject
Cell Cycle Arrest
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COEXISTS_WITH
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Resting Phase, Cell Cycle
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Ribosomal Proteins / Viral Nonstructural Proteins / Ribosome Subunits, Small, Eukaryotic / Host-Pathogen Interactions / SARS-CoV-2 / Lysine Topics: Vaccines Limits: Humans Language: English Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Ribosomal Proteins / Viral Nonstructural Proteins / Ribosome Subunits, Small, Eukaryotic / Host-Pathogen Interactions / SARS-CoV-2 / Lysine Topics: Vaccines Limits: Humans Language: English Year: 2021 Document Type: Article