Posted on March 14, 2020 at 12:00 AM
Scientists now established microscopic characteristics that could render the pathogen more contagious than the SARS virus— and serve as targets for the medications.
With the number of coronavirus infections reaching 100,000 people around the world, researchers are working to explain what makes it so easy to spread.
A handful of genetic and molecular analyzes have identified a central aspect of the virus— a protein on its surface— that may explain why it can so readily infect human cells.
Certain researchers are studying the gateway through which the current coronavirus is accessing human tissues— a cell membrane receptor. Both the cell receptor and the protein virus provide new drug targets to kill the pathogen, but experts agree it is too early to be certain.
"Comprehension of virus dissemination is crucial to its control and potential protection," says David Veesler, a systemic virologist at the University of Washington in Seattle, who reported his team's results on the biomedical preprint website bioRxiv on 20 February 1.
The new virus spreads much more easily than the one that caused extreme acute respiratory syndrome, or SARS (also a coronavirus), and has killed more than 10 times the number of individuals who contracted SARS.
Coronaviruses use a' spike' protein to infect a cell, which attaches to the cell membrane, a mechanism that is activated by different cell enzymes. The latest coronavirus ' genomic study has shown that the spike protein differs from that of close relatives and indicates that the protein has a spot on it that is regulated by a host-cell enzyme named furin.
This is important because furin is present in many human tissues, including the kidneys, liver and small intestines, suggesting the virus has the ability to invade several organs, says Li Hua, a structural biologist at Huazhong University of Science and Technology in Wuhan, China, where the epidemic started. The result could explain some of the symptoms found in people with coronavirus, such as liver failure, says Li, who co-authored a virus genetic analysis posted on the preprint website ChinaXiv on February 23,2. SARS and other coronaviruses of the same genus as the current virus lack activation sites for furin, he says.
Yet some researchers remain skeptical about overstating the activation site's function in making the coronavirus propagate faster. "We don't know whether it's going to be a big deal or not," says Jason McLellan, a structural biologist at Austin's Texas University, who co-authored another coronavirus structural study released in Science on February 20, 5.
Some experts remain skeptical about matching furin activation sites on flu viruses to those on the current coronavirus. Peter White, a virologist at the University of New South Wales in Australia, says the haemagglutinin protein on the surface of flu viruses is not identical or related to the spike protein in coronaviruses.
And the flu virus that triggered the worst recorded pandemic, the Spanish flu pandemic of 1918, doesn't even have a site for furin activation, says Lijun Rong, a virologist at Chicago's University of Illinois.
Whittaker says experiments are required to check the role of the activation site in cell or animal models. "Coronaviruses are unreliable and it always turns out positive predictions are false," he says. His research is currently investigating how site deletion or alteration affects the function of the spike protein.
A further function that may clarify why the current coronavirus infects human cells so effectively has been reported by the McLellan group in Texas. Their tests found that the spike protein binds to a human cell receptor— known as angiotensin-converting enzyme 2 (ACE2) — at least ten times stronger than the spike protein in the SARS virus did.
Veesler's team has observed that the spike protein binds to the ACE2 receptor with a high affinity, indicating the receptor is another possible candidate for vaccines or therapies. For example, a drug that blocks the receptor may make it more difficult for coronavirus to get into cells.
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