Yale Scientists Discover Genes That Could Be COVID Treatment Targets

Researchers at the Yale School of Medicine have identified genes that could be future targets for COVID-19 treatments.

In a partnership with the Broad Institute of MIT and Harvard, researchers at the School of Medicine’s Department of Immunology performed a genome-wide CRISPR screen, which evaluated each of the 20,000 preselected genes in the African green monkey genome that could affect coronavirus infections. This technique allowed researchers to quickly and effectively evaluate the genetic information from over a million modified cells.

According to assistant professor of laboratory medicine and immunobiology Craig Wilen, using a genetically modified virus called a CRISPR library, certain genes of interest were knocked out in the monkey cells in order to stop their products from being made and used in the cell. The cells were then infected with the coronavirus, and those that survived were analyzed to detect what genes were knocked out and could be affecting viral infection. The results pointed to over 25 possible host genes related to infection, but two specific hits — for receptor and enzyme encoding genes — seemed most promising as treatment targets.

“We think it’s possible that you could develop drugs that affect human targets,” Wilen said. “And the advantage there is it would be conserved and function across different coronaviruses.”

Jin Wei, the study’s primary author and a postdoctoral associate at Wilen’s lab, explained that he was directly involved in identifying the host genes critical to coronavirus infections.

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Mia Madel Alfajaro, another postdoctoral associate at Wilen’s lab, explained that they found two important genes during their screening process that, when absent, helped cells survive the virus infection. One of them encodes the SARS-Cov-2 receptor, while the other is translated into an enzyme that aids the coronavirus in entering the cell.

Scientists at the Broad Institute provided the Yale researchers with the CRISPR library to be used in the monkey cells and the analyses they ran on the surviving cells’ genetic material.

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Wei and Doench believe one of the main findings of the study comes from the comparison between SARS-CoV-2 and another coronavirus, MERS-CoV. These genetic hits that affect coronaviruses in general could be useful in finding “pan-coronavirus” treatments, according to Wilen.

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