Biologist Vanderbilt Yi Ren is part of a team that has identified a new transport of SARS-CoV-2 protein and found that blocking its function can inhibit virus reproduction in host cells. This opens the potential for new therapeutic targets for COVID-19.
The article, “Nsp1 Protein of SARS-CoV-2 disrupts the mRNA export mechanism to inhibit host gene expression,” was published in the journal Advances in science on 5 February.
A 2019 study by Ren showed that protein NS1, a component that influences the severity of influenza A virus, targets the host protein NXF1. The main function of NXF1 is to provide the signal for messenger RNA to enter the cytoplasm so that it can be converted to protein. Since the beginning of the COVID-19 pandemic, Ren has been applying his knowledge of viral gene and protein expression techniques to better understand SARS-CoV-2.
The researchers took early action in early 2020, discovering that SARS-CoV-2 behaves like influenza A in mRNA identification. “We identified an interaction between the Nsp1 virulence protein of SARS-CoV-2 and the host protein NXF1 – which we investigated for the influenza A virus,” said Ren, associate professor of biochemistry and Associate Faculty of Chancellor. “Because we were very familiar with NXF1, we were able to confirm that SARS-CoV-2 has the same interaction with virus host. ”
Ren and her colleagues have also found that an excess of NXF1 inhibits the viral infection of human cells. This could mean that inhibition of Nsp1 activity will enable infectious cells to express the genes that attack the virus, Ren explains. Within her laboratory and the Center for Structural Biology, Ren is working to gain a detailed understanding of how Nsp1 targets its host factor. With this information, other researchers will have a solid foundation for considering structure-based drug design.
In principle, this work is helpful in studying future viruses. Viruses are very talented, Ren explains, because they can take advantage of the same path to a host cell through very different mechanisms. Learning more about the behavior of each virus can promote faster development of therapeutic treatment.
The research was supported by the National Institutes of Health, Canadian Institutes of Health Research, the Center for Research on Influenza Pathogenesis, a Center of Excellence funded by the National Institute of Allergy and Infectious Diseases, for Advanced Research Projects in Defense Agency and others.