- A team of 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.
- Leading virologist at Mount Sinai, Dr. Benjamin tenOever, 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.
A team of scientists say they have identified the genes that can protect human cells against Covid-19. The scientists from the New York Genome Center, New York University and Icahn School of Medicine at Mount Sinai used CRISPR, a technology that allows them to alter DNA sequences, to make their discoveries.
The discovery comes after an eight-month screen of all 20,000 genes in the human genome led by Dr. Neville Sanjana at the New York Genome Center. Leading virologist at Mount Sinai, Dr. Benjamin tenOever, developed a series of human lung cell models for the coronavirus screening to better understand immune responses to the disease and co-authored the study.
Their study, published online last month by Cell, will appear in the scientific peer-reviewed journal's Jan. 7 print issue.
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.
The breakthrough comes at a time when drug makers such as Pfizer, Oxford-AstraZeneca and Moderna are fast-forwarding vaccine and therapeutics to treat Covid-19. On Friday, Pfizer and BioNTech requested emergency authorization from the FDA for their Covid vaccine that contains genetic material called messenger RNA, which scientists expect provokes the immune system to fight the virus.
According to a press release from NYU and the New York Genome Center, the team employed a broad range of scientific techniques to analyze genetic dependencies between viruses and their human hosts.
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 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 researchers discovered that the genes most likely to be responsible for aiding the virus' ability to replicate were clustered in several specific protein groups that are involved in moving proteins to and from cell membranes.
Cholesterol and the virus
The research team also identified drugs that are currently on the market for different diseases that they claim block the entry of Covid-19 into human cells by increasing cellular cholesterol. 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.
- Ilomastat, brand name Galardin, it's a matrix metalloprotease inhibitor, that now being manufactured by many companies; a chemotherapy agent, with applications for skincare and anti-aging products.
The other five drugs that were tested — called PIK-111, Compound 19, SAR 405, Autophinib, ALLN -- are used in research but are not yet branded and used in clinical trials for existing diseases.
Overall, the findings offer insight into novel therapies that may be effective in treating Covid-19 and reveal the underlying molecular targets of those therapies.
The bioengineers in New York were working on other projects with gene-editing technology from CRISPR but quickly pivoted to studying the coronavirus when it swept through the metropolitan area last March. "Seeing the tragic impact of Covid-19 here in New York and across the world, we felt that we could use the high-throughput CRISPR gene editing tools that we have applied to other diseases to understand what are the key human genes required by the SARS-CoV-2 virus," said Sanjana in the press release.
As he explained further to CNBC, "current treatments for SARS-CoV-2 infection currently go after the virus itself, but this study offers a better understanding of how host genes influence viral entry and will enable new avenues for therapeutic discovery."
Previously, Sanjana has used the CRISPR technology screens to identify a wide array of diseases, from muscular dystrophy to several types of cancer.
"The hope is that the data from this study— which pinpoints required genes for SARS-CoV-2 infection — could in the future work be combined with human genome sequencing data to identify individuals that might be either more susceptible or more resistant to Covid-19," Sanjana said.
The New York team is not the first to use CRISPR gene editing techniques to fight Covid-19. Other bioengineering groups at MIT and Stanford have been using CRISPR to develop ways to fight the SARS-CoV-2 and develop diagnostic tools for Covid-19.
The potential for using CRISPR to eliminate viruses has already generated some enthusiasm in the research community. Last year, for example, Excision BioTherapeutics licensed a technology from Temple University that uses CRISPR, combined with antiretroviral therapy, to eliminate HIV, the virus that causes AIDS.
CORRECTION: This article had been updated to include additional source attribution.