Study published in the journal cell online revealed that by targeting a single protein cell which appears essential for SARS-CoV-2 to replicate could control the spread of the virus.
The latest finding from a pair of studies led by researchers at NYU Grossman School of Medicine and NYU Langone Health’s Perlmutter Cancer Center and colleagues at Rockefeller University revealed that a protein named TMEM41B is necessary for the Covid-19 virus to reproduce and spread to other cells and hence is a potential weakness that could be targeted by future therapies.
The molecule, known as transmembrane protein 41 B (TMEM41B), is believed to help shape the fatty outer membrane that protects the virus’ genetic material while it replicates inside an infected cell and before it infects another.
In a series of experiments, researchers compared how the Covid-19 virus reproduces in infected cells to the same processes in two dozen deadly flaviviruses, including those responsible for yellow fever, West Nile and Zika disease.They also compared how it reproduces in infected cells to three other seasonal coronaviruses known to cause the common cold.
Studies’ co-senior investigator John T. Poirier, PhD said, “Together, our studies represent the first evidence of transmembrane protein 41 B as a critical factor for infection by flaviviruses and, remarkably, for coronaviruses, such as SARS-CoV-2, as well,”
Poirier, an assistant professor of medicine at NYU Langone Health claimed that the first step in confronting a new contagion like Covid-19 is to map the molecular landscape to see what possible targets one has to fight.”Comparing a newly discovered virus to other known viruses can reveal shared liabilities, which we hope serve as a catalogue of potential vulnerabilities for future outbreaks,” added Poirier.
Poirier, who also serves as director of the Preclinical Therapeutics Program at NYU Langone and Perlmutter Cancer Center said, “While inhibiting transmembrane protein 41 B is currently a top contender for future therapies to stop coronavirus infection, our results identified over a hundred other proteins that could also be investigated as potential drug targets,”
In addition to TMEM41B, some 127 other molecular features were found to be shared among SARS-CoV-2 and other coronaviruses. These included common biological reactions, or pathways, involved in cell growth, cell-to-cell communication, and means by which cells bind to other cells.
Interestingly, Poirier notes, mutations, or alterations, in TMEM41B are known to be common in one in five East Asians, but not in Europeans or Africans.
Another study finding was that cells with these mutations were more than 50 per cent less susceptible to flavivirus infection than those with no gene mutation.Poirier says more research is needed to determine if TMEM41B mutations directly confer protection against Covid-19 and if East Asians with the mutation are less vulnerable to the disease.
The research team next plans to study the other common pathways for similar potential drug targets after mapping out TMEM41B’s precise role in SARS-CoV-2 replication so they can start testing treatment candidates that may block it. Poirier adds that the research team’s success in using CRISPR to map the molecular weaknesses in SARS-CoV-2 serves as a model for scientists worldwide for confronting future viral outbreaks.
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