BREAKING! COVID-19 Research: German Study Reveals That Spike Protein Nsp1 Of SARS-CoV-2 Responsible For Shutting Down Host Protein Production
Source: COVID-19 Research Jul 20, 2020 3 years, 9 months, 6 days, 18 hours, 27 minutes ago
COVID-19 Research: German researchers and virologists from the University Of Munich and Institute of Molecular Virology, ULM University have discovered that the spike protein Nsp1 from the SARS-Cov-2 has a central role in weakening the host anti-viral immune response by effectively shutting down production of proteins in the host.
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It was found that the SARS-CoV Nsp1 induces a near-complete shutdown of host protein translation by a two-pronged strategy: first, it binds the small ribosomal subunit and stalls canonical mRNA translation at various stages during initiation and in the second method, Nsp1 binding to the ribosome leads to endonucleolytic cleavage and subsequent degradation of host mRNAs.
The research findings were published in the journal: Science.
https://science.sciencemag.org/content/early/2020/07/16/science.abc8665
Though SARS-Cov-2 features additional inhibitors of host innate immune defenses, targeting the interaction of this protein, Nsp1, with the host may be an important therapeutic strategy, the researchers say. A major virulence factor of SARS-CoVs, including the SARS-CoV-2 virus causing the current COVID-19 pandemic, is the protein Nsp1.
It was found that upon infection, The Nsp1 protein suppresses vital protein production in the host, including production of proteins active in cellular anti-viral defense mechanisms, by binding to the cell's protein production machinery, the ribosome. Targeting the pocket on the ribosome that Nsp1 binds to could be an important potential therapeutic strategy.
Typically in all living cells, the task of synthesizing proteins is performed by complex molecular cellular organelles known as ribosomes. Ribosomes interact with messenger RNAs (mRNAs), which serve as blueprints for protein synthesis, and translate the nucleotide sequence of each mRNA into the amino-acid sequence of the corresponding protein. The amino-acid sequence in turn determines the shape and biological function of each individual protein. Ribosomes consist of two distinct subunits, and Nsp1 binds to the smaller one - the 40S subunit. The mRNA initially binds to the small subunit, prior to the latter's interaction with the 60S subunit to form the cavity through which the mRNA is then threaded.
Professor Dr Matthias Thoms from the Gene Center Munich, Department of Biochemistry, University of Munich
, and fellow researchers set out to structurally characterize the Nsp1 of SARS-CoV-2 bound to the ribosome. As part of their approach, they tested the ability of a mutant form of Nsp1, known as mt-Nsp1, to affect protein production related to host immune response, in both in vitro and in vivo experiments. The mutant version did not bind in the same way, the researchers showed, and did not shut down host translation (or protein production). Through further experiments, the study teams' results demonstrate that SARS-CoV-2 Nsp1 almost completely prevents production of various immune molecules that fight viral infection, including interferons.
Professor Dr Roland Beckmann, the corresponding researcher of the study, also from the Gene Center Munich, Department of Biochemistry, University of Munich told Thailand Medical News, &
;quot;Our data establish that one of the major immune evasion factors of SARS-CoV-2, the spike protein Nsp1, efficiently interferes with the cellular translation machinery resulting in a shut-down of host protein production.”
He added, “The research findings may provide a starting point for rational structure-based drug design targeting the interaction between Nsp1 and the ribosome.”
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