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CRISPR scientists claim identified genes that protect against Covid

COVID-19 coronavirus molecule, March 24, 2020.

CDC | API | Gamma Rafo via Getty Images

A team of CRISPR scientists at New York University’s New York Genome Center and Mount Sinai School of Medicine said they have identified genes that can protect human cells from Covid-19, the disease that caused infections in more than 40 million people. .. One million people have died worldwide.

The discovery was made after eight months of screening all 20,000 genes in the human genome, led by Dr. Neville Sanjana of the New York Genome Center. Dr. Benjamin ten Oever, a leading virologist at Mount Sinai, has developed a series of human lung cell models for coronavirus screening to better understand the immune response to the disease and co-author the study.

Their study published online last month by Cell, It will be published in a printed matter published on January 7th in a scientifically peer-reviewed journal.

I had two goals. Identifying genes that make human cells more resistant to the SARS-CoV-2 virus. Test existing drugs on the market that may help stop the spread of the disease.

Breakthroughs come when pharmaceutical companies such as Pfizer, Oxford-AstraZeneca, and Moderna are fast-forward vaccines and remedies to treat Covid-19. On Friday, Pfizer and BioNTech requested the FDA to urgently permit a Covid vaccine containing a genetic material called messenger RNA. It expects scientists to stimulate the immune system to fight the virus.

To better understand the complex relationships between host and viral genetic dependencies, the team used a wide range of analytical and experimental methods to validate the results. This integrated approach included genome editing, single cell sequencing, confocal imaging, and computational analysis of gene expression and proteomics datasets.

After thorough research, scientists and doctors have found that the virus contains human cells, including RAB7A, a gene that appears to regulate the ACE-2 receptor that the virus uses to bind and invade cells. It claims to have found 30 genes that prevent it from infecting the virus. The first contact of spike proteins with human cells is via the ACE-2 receptor.

“Our findings confirm that scientists believe that the role of the ACE-2 receptor in infection is true. It holds the key to unlocking the virus,” said Dr. ten Oever. Said. “It also became clear that we needed a toolbox of components for the virus to infect human cells. In order for the virus to invade human cells, everything needs to be aligned.”

The team found that top-ranked genes, the genes whose loss significantly reduces viral infections, cluster into a small number of protein complexes such as vacuolar ATPases, retromers, commanders, Arp2 / 3, and PI3K. Did. Many of these protein complexes are involved in protein transport to and from cell membranes.

“We are very pleased to see multiple genes in the same family as top-ranked hits on the genome-wide screen, which gives us a high degree of confidence that these protein families are essential to the viral life cycle. Obtained, or successful virus replication. ” Dr. Zharko Daniloski, a postdoctoral fellow at the Sanjana Institute and co-lead author of the study, said.

Using proteomics data, they found that some of the higher-ranked host genes interacted directly with the virus’s own proteins, emphasizing its central role in the virus’s life cycle. The team also analyzed common host genes required for other viral pathogens such as Zika fever and H1N1 pandemic influenza.

Cholesterol and virus

The researchers also identified drugs currently on the market for a variety of diseases that claim to block the invasion of Covid-19 into human cells by increasing cell cholesterol. In particular, they found that the three drugs currently on the market are more than 100 times more effective in blocking the entry of the virus into human lung cells.

  • Amlodipine, Brand name Norvasc, by Pfizer, to treat hypertension and angina.
  • Tamoxifen, The brand name Soltamox by Fortovia Therapeutics, an estrogen modulator for the treatment of breast cancer.
  • Iromastat, Brand name Galaldine, it is a matrix metalloproteinase inhibitor and is currently manufactured by many companies. Chemotherapeutic agents applied to skin care and anti-aging products.

Five other drugs tested — called PIK-111, Compound 19, SAR 405, Autofinib, ALLN -Used in research, but not yet branded and used in clinical trials of existing diseases.

Our findings confirm that scientists believe that the role of ACE-2 receptors in infection is true. It holds the key to unlocking the virus.

Their findings provide insights into new therapies that may be effective in treating Covid-19 and reveal the molecular targets that underlie those therapies.

Bioengineers in New York were working on other projects using CRISPR’s gene editing technology, but when they swept the metropolitan area last March, they quickly turned to coronavirus research. .. “See the tragic effects of Covid-19 here in New York and around the world and use high-throughput CRISPR gene editing tools applied to other diseases to understand what the key human genes are needed. I felt. SARS-CoV-2 virus. “

Dr. Neville Sanjana of the New York Genome Center and his team have identified genes that can use CRISPR to protect human cells from Covid-19.

New York Genome Center

As he explained, “Current treatments for SARS-CoV-2 infection are currently chasing the virus itself, but this study provides a better understanding of how host genes affect viral invasion. It provides and enables new paths for the discovery of cures. “

Previously, Dr. Sanjana applied a genome-wide CRISPR screen to identify genetic factors in a variety of diseases, including drug resistance to melanoma, immunotherapy failure, lung cancer metastasis, innate immunity, congenital metabolic disorders, and muscular dystrophy. ..

“It is hoped that future studies will be able to combine data from this study to identify genes required for SARS-CoV-2 infection with human genome sequencing data to identify individuals who are more susceptible or resistant to Covid-. 19 “said Dr. Sanjana.

The New York team is not the first team to fight Covid-19 using CRISPR gene editing technology. MIT and other biotechnology groups at Stanford are developing methods to fight SARS-CoV-2 using CRISPR and developing diagnostic tools for Covid-19.

The possibility of using CRISPR to eliminate the virus has already generated some enthusiasm for the research community. For example, last year Excision BioTherapeutics License Temple University’s technology that uses CRISPR in combination with antiretroviral therapy to eliminate HIV, the virus that causes AIDS.

CRISPR scientists claim identified genes that protect against Covid

Source link CRISPR scientists claim identified genes that protect against Covid

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