Researchers on Yale University And the Broad Institute MIT And Harvard came in contact with millions of cells COVID-19 And identified MERS viruses and dozens of genes that enable both viruses to replicate into cells and even those that slam the door of the virus.
Researchers say the pro-viral and anti-viral role of these genes will help guide scientists in developing new therapies to combat COVD-19.
These findings were reported in the journal Today (October 26, 2020) Cell.
How Scientists Previously SARS-CoV-2 The coronavirus, which causes COVID-19, attaches to and invades cells, but little is known about why some cells are more susceptible to infection. The susceptibility of host cells to infection can help understand the genetics behind why some people exposed to the virus experience few or no symptoms and others become extremely ill or die.
For the study, researchers introduced a genome-wide screen of lines of green monkey cells that die after exposure to SARS-COV-2 rather than commonly used human cell lines. The first screens allowed researchers to simultaneously track the interactions of viruses and cells. The screens confirmed previous findings that the ACE-2 gene, which encodes a receptor on the cell surface, promotes infection by SARS-CoV-2.
However, the screens identified two new pro-viral protein complexes and a third, which helps prevent infection. They found that the SWI / SNF complex, which turns genes on and off, and HMBB1, which has a variety of functions, including inflammation regulation, are linked to increased cell death after infection.
The researchers then introduced small molecular drugs that inhibit the action of two known gene products and they could increase the survival of cells after infection in dishes.
In contrast, the histone H3 complex, which helps regulate the expression of genes within the cell nucleus, provides a protective effect, inhibiting the ability of cells to infect and kill.
“It’s important to understand the wide variety of responses to COVID-19, for example, to why people die of old age,” said Craig Wiley, Yale’s assistant professor of laboratory medicine and immunology and co-author of the paper. . “We have identified both proviral and antiviral genes that can help us predict what serious illness is likely to occur and what types of drugs are helpful or harmful in treating patients.”
Villain noted that the information could not only be helpful for the current epidemic, but would also help prepare for the emergence of an emerging coronavirus in the future.
References: Jin V, Mia Medal Alphazaro, Peter C. Dewardt, Ruth e. Hannah, William J. Lu-Culligan, Wesley L. Genome-wide CRISPR screens by CE, reveal host factors for SARS-CV-2 infection. Madison S. Strain, Sh Shang Ng-Min Zhang, Vincent R. Graziano, Cameron O. Smitz, Jennifer S. Chen, Madeleine C. Mankowski, Renata b. Filler, Neil G. Patil, Huakui Cheney, Kasopefoluva y. Augantio, Laura Abriola, Yulia V. Surovatseva, Robert c. Orchard, Benhar Lee, Brett D. G. Doench and Craig b. Villain, 26 October October 2020, Cell.
DOI: 10.1016 / j.cell.2020.10.028
Yale’s Jin Wei was the first author of the study, which was primarily funded by the Burrows Welcome Fund and the Ludwig Family Foundation.
