+353 (1) 685 6929 It has been known for a while now that genetic predispositions can explain why some people are severely affected by Covid-19 while others barely experience any symptom. But aside from genetic factors that can likely increase an individual’s risk to get a severe case of Covid-19, it turns out that there are also human genes that can protect you from the virus.
CRISPR scientists at the New York Genome Center in New York University and the Icahn School of Medicine at Mount Sinai have teamed up to study genes that could possibly protect human cells against Covid-19.
Led by Dr. Neville Sanjana from the New York Genome Center, the team conducted an eight-month screening of all 20,000 genes in the human genome. The co-author of the study, Dr. Benjamin tenOever, a leading virologist from Mount Sinai, meanwhile developed a series of human lung cell models for the screening to understand the body’s immune responses to the virus.
For this study, the team’s goals are to identify genes that could make humans more resistant to the SARS-CoV-2 virus and, in line with this, to identify existing medications that could help stop the disease.
The team used analytical and experimental approaches to conduct the study, including genome editing, confocal imaging, single cell sequencing, and computational analyses of proteomic datasets and gene expression.
Through these methods, the team was able to identify 30 genes that are able to block the virus and keep it from infecting human cells. They identified the gene RAB7A, in particular, as a gene that could regulate the ACE-2 receptor that the virus uses to enter a cell.
According to Dr. tenOever, the ACE-2 receptor holds the key to unlocking the virus. The study also revealed that there are several factors that need to be in alignment for the virus to be able to infect the cells.
Aside from genes that block the virus’s entry to the cells, the team also identified several gene hosts that play a role in viral infection. These genes, they found out, directly interact with the SARS-CoV-2 virus’ own proteins, confirming their role in the viral life cycle.
Dr. Zharko Daniloski, co-first author of the study and a postdoctoral fellow in the Sanjana Lab, believes that identifying these multiple genes means a higher likelihood of identifying protein families crucial to the entry and replication of the virus. The team also analysed common host genes involved in the life cycle of other viruses such as Zika and H1N1.
The team’s second goal for this study is to identify existing drugs that could block the entry of Covid-19.
The team found three existing drugs that are highly effective in stopping viral entry into human lung cells. These three drugs are amlodipine (used to treat high blood pressure and angina), tamoxifen (an estrogen modulator used to treat breast cancer), and ilomastat (a matrix metalloprotease inhibitor and chemotherapy agent).
The team also tested five other drugs that are not yet branded and are still undergoing clinical trials for existing diseases. These drugs are PIK-111, Compound 19, SAR 405, Autophinib, and ALLN.
Aside from identifying drugs that can possibly block the entry of the virus, the team believes that their findings could prove to be effective in managing the symptoms of Covid-19. Team leader Dr. Sanjana explains that current treatments for the virus infection target the virus itself, but their study offers a new perspective. Finding the links between the virus life cycle to genetic profiles can open new avenues for therapeutic discovery.
He adds that the data of the study could be combined with future human genome sequencing data to identify individuals that are either susceptible or resistant to Covid-19.
Prior to the Covid-19 pandemic, Dr. Sanjana applied genome-wide screening to identify genetic factors behind diseases like lung cancer, muscular dystrophy, and inborn metabolic disorders.
Clinical DNA testing has also proven to be effective in identifying predispositions to medical conditions such as autoimmune disorders, neurological diseases, and cardiovascular diseases.
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