• The Financial District


A team of CRISPR scientists at the New York Genome Center, New York University and Icahn School of Medicine at Mount Sinai say they have identified the genes that can protect human cells against COVID-19, Lori Ioannou reported for the broadcast network CNBC.

Dr. Benjamin tenOever, a leading virologist at Mount Sinai, developed a series of human lung cell models for coronavirus screening to better understand immune responses to the disease and co-authored the study. The goal was two-fold: to identify the genes that make human cells more resistant to SARS-CoV-2 virus; and test existing drugs on the market that may help stop the spread of the disease. Their study, published online last month by Cell, will appear in the scientific peer-reviewed journal’s Jan. 7 print issue.

After intensive research the scientists and doctors claim they have found 30 genes that block the virus from infecting human cells including RAB7A, a gene that seems to regulate the ACE-2 receptor that the virus binds to and uses to enter the cell. The spike protein’s first contact with a human cell is through ACE-2 receptor. “Our findings confirmed what scientists believe to be true about ACE-2 receptor’s role in infection; it holds the key to unlocking the virus,” said Dr. tenOever. “It also revealed the virus needs a toolbox of components to infect human cells. Everything must be in alignment for the virus to enter human cells.”

The team discovered that the top-ranked genes — those whose loss reduces viral infection substantially — clustered into a handful of protein complexes, including vacuolar ATPases, Retromer, Commander, Arp2/3, and PI3K. Many of these protein complexes are involved in trafficking proteins to and from the cell membrane. “We were very pleased to see multiple genes within the same family as top-ranked hits in our genome-wide screen. This gave us a high degree of confidence that these protein families were crucial to the virus lifecycle, either for getting into human cells or successful viral replication,” said Dr. Zharko Daniloski, a postdoctoral fellow in the Sanjana Lab and co-first author of the study. In particular, they found three drugs currently on the market were more than 100-fold more effective in stopping viral entry in human lung cells: Amlodipine, brand name Norvasc, by Pfizer, to treat high blood pressure and angina; Tamoxifen, brand name Soltamox by Fortovia Therapeutics, an estrogen modulator, to treat breast cancer, and; Ilomastat, brand name Galardin, a matrix metalloprotease inhibitor manufactured by many companies and a chemotherapy agent with applications for skincare and anti-aging products.

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