Scientists have determined how the novel coronavirus, which causes COVID-19, inhibits the synthesis of proteins in infected cells, and have shown that it effectively disarms a part of the immune system, findings that may aid in the development of novel therapeutics against the deadly disease.
The study, published in the journal Science, demonstrated that nonstructural Protein 1 (Nsp1) made by the novel coronavirus SARS-Cov-2 can have a devastating effect on host cells. According to the researchers, including those from the University of Munich in Germany, Nsp1 is one of the central weapons used by the virus to ensure its own replication and propagation in human hosts.
They said Nsp1 was identified as a disease contributing factor following the outbreak of the related 2002-03 SARS pandemic virus. Scientists who studied the SARS virus had shown that it inhibited protein synthesis in infected cells.
“Although 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 noted.
Upon infection, they said SARS-CoV-2 suppressed protein production in the host, including that of proteins active in cellular anti-viral defense mechanisms. The virus did this by binding to the cell’s protein production machinery, the ribosome, the study noted.
According to the scientists, targeting the specific part of the ribosome that Nsp1 binds to could be an important potential therapeutic strategy. In the research, the scientists structurally characterised the Nsp1 of SARS-CoV-2 bound to the ribosome. They tested the ability of a modified version form of Nsp1, known as mt-Nsp1, to affect protein production related to host immune response.
According to the study, the mutant version did not bind in the same way and did not shut down host cell protein production. The scientists also demonstrated that SARS-CoV-2 Nsp1 almost completely prevented production of various immune molecules that fight viral infection, such as interferons.
“Our data establish that one of the major immune evasion factors of SARS-CoV-2, Nsp1, efficiently interferes with the cellular translation machinery resulting in a shut-down of host protein production,” the study noted. According to the scientists, the findings may provide a starting point for rational structure-based drug design, targeting the interaction between Nsp1 and the ribosome.
