A major collaboration of international experts from various medical, genomic and biological fields lead by Northeastern’s Center for Complex Network Science Research has identified that the SARS-Cov-2 coronavirus is able to target 332 human proteins and also has a variety of binding sites, not just the four that was initially discovered including ACE-2 receptors.
The new research indicates that SARS-CoV-2 coronavirus can be described as the most potent virus ever known to mankind. With more details of the structure of the new virus genome and also the way it interacts with the various human proteins, the researchers have also identified 40 new drugs that could be repurposed for usage to treat COVID-19.
The study findings, come from a modeling tool for infection dynamics based on network science utilizing complex math, physics, and computing. https://www.biorxiv.org/content/10.1101/2020.03.22.002386v1
The new toolset mapped the way proteins within human cells behave after a cell is hijacked with SARS-CoV-2, the new coronavirus that causes the COVID-19 illness.
Dr. Albert-László Barabási, Robert Gray Dodge Professor of Network Science and University Distinguished Professor of physics at Northeastern told Thailand Medical News, “We have prioritized many more drugs, but there are 40 that we are actually trying to move forward.” https://covid.barabasilab.com/2020/04/network-based-embedding-of-all-human.html
Dr. Barabási’s team is already in discussions with experimental biologists at Harvard to begin testing these drugs in human cell lines.
The varied interactions of different kinds of proteins within our cells play a key role in orchestrating the complex biochemical reactions that control our bodies. That’s why, Dr. Barabási says, the best way to understand how viruses spread is to identify the whole set of the molecular interactions within human cells, and the networks those interactions create as proteins interact with genetic material inside the cell.
He added, “Virtually every disease that we have spreads through a cellular network. The SARS-CoV-2 virus has a particularly fast way of doing that because it is invading the cell, in this case with 26 proteins, effectively doing a very fast and effective perturbation on multiple points of the network.”
The AI model, which Barabási originally developed with a group of researchers in 2012 to study other human viruses, also predicted that SARS-CoV-2 could potentially attack cells in the brain. That finding, the report states, could help explain recent reports that early COVID-19 symptoms include the loss of the sense of smell and taste.
The novel list of drugs adds to other potential treatments that researchers have already identified. Barabási’s model identified several of those drugs, as well as others that had not been considered.
Dr. Barabási further added, “The reason we can do so is that we are not limiting ourselves to drugs that hit those proteins that the virus targets. We can also discover drugs that hit in the neighborhood that the virus targets.”
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Rapidly after entering the body, SARS-CoV-2 hijacks human cells and retools them into virus-replicating machines. The virus relies on the set of protruding proteins for which all other strains of coronaviruses are named ie a set of spikes resembling those of a crown. As those viral proteins latch on to the proteins of a healthy cell, they disrupt basic functions within it and make it churn out millions of more versions of the virus.
The initial step in modeling viral infection was understanding which proteins SARS-CoV-2 attacks to hijack human cells. Researchers recently reported that there are 332 of those proteins.
Dr. Barabási’s toolset modeled the role of the 332 proteins targeted by the coronavirus and predicted other mechanisms those proteins could trigger within the cell to lead to the symptoms of COVID-19.
The new model focused on drugs that could fight the virus not just by neutralizing its spike proteins as they first targeted human cells, but by disrupting other interactions within human proteins and genes. These treatments target areas within the cell where the virus works, instead of directly targeting the virus, and could influence the way the proteins that SARS-CoV-2 needs to thrive are encoded.
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Dr. Barabási adds, “By simply identifying what neighborhood the virus hits, we can identify what are the potential drugs that are hitting in the same neighborhood, and therefore could be effective against the virus.”
He warns that the best drug candidates will probably be those that don’t target the proteins that SARS-CoV-2 initially attacks but work within the same subcellular neighborhood.
He explained, “Very few drugs on the market are directly targeting the disease proteins themselves. Simply knowing what proteins the virus targets will not be enough for us to find the drug, we need to understand very well the network’s neighborhoods of those hitting points.”
Dr. Marinka Zitnik, an assistant professor of biomedical informatics at Harvard Medical School, used machine learning to help Barabási’s group comb through available data on drugs already on the market or in clinical trials that could be repurposed to treat COVID-19.
Dr. Joseph Loscalzo, Hersey Professor of the Theory and Practice of Medicine at Harvard Medical School, chairman of the Department of Medicine, and physician-in-chief at Brigham and Women’s Hospital, helped the team discard potential drug candidates that could be significantly toxic or impossible to administer intravenously or orally.
The research team’s progress and updates are being released online as soon as they are available, in an effort to help the global scientific community as it works at breakneck speed to solve the COVID-19 crisis. A report with more data and information will be released as a preprint online and submitted to a peer-reviewed journal for publication.
Dr. Barabási concluded, “We are releasing the results as they emerge so that others can immediately build on them and have the research. There is such an imminent need to make progress in this area, that we cannot be slaves of our existing academic or business models.”
SurvivalDan101 will also be covering more on the newer studies involving herbs, phytochemicals, drug supplements and other pharmaceutical candidates that are being studied and also progress of these studies.
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