In this file:
· Why does SARS-CoV-2 spread so easily?
· COVID-19: the biology of an effective therapy
· NYT: Hundreds of Scientists Scramble to Find a Coronavirus Treatment
Why does SARS-CoV-2 spread so easily?
What structural features of the SARS-CoV-2 virus allow it to attack human cells and spread so efficiently? We round up some of the key emerging evidence.
Written by Ana Sandoiu, Fact checked by Mohamed Elsonbaty Ramadan, M.S.
Medical News Today - March 17, 2020
The new coronavirus, called SARS-CoV-2, has caused more than 168,000 infections globally, leading to the health condition COVID-19.
In an effort to understand the nature of this highly contagious virus, researchers have been drawing comparisons with the SARS coronavirus (SARS-CoV) — the causative agent of severe acute respiratory syndrome, better known as SARS.
SARS-CoV and SARS-CoV-2 share 86% of the same genomic sequence. SARS was deemed “the first pandemic of the 21st century” because it spread quickly from continent to continent, causing more than 8,000 infections in 8 months — with a 10% case fatality ratio.
However, SARS-CoV-2 is spreading much faster. In 2003, 8,098 SARS cases, with 774 deaths, occurred within 8 months. By contrast, within 2 months of the start of the SARS-CoV-2 outbreak, the new coronavirus infected more than 82,000 people, causing more than 2,800 deaths.
So what makes the new coronavirus so much more infectious? We take a look at some of the latest evidence that helps answer this question.
Specifically, a few genetic studies have investigated the microscopic structure of the virus, a key protein on its surface, and a receptor in human cells that may, collectively, explain why the virus can attack and spread so easily.
Spike protein on the new coronavirus
Spike proteins are what coronaviruses use to bind to the membrane of the human cells that they infect. The binding process is activated by certain cell enzymes.
SARS-CoV-2, however, has a specific structure that allows it to bind “at least 10 times more tightly than the corresponding spike protein of [SARS-CoV] to their common host cell receptor.”
Partly, this is due to the fact that the spike protein contains a site that recognizes and becomes activated by an enzyme called furin.
Furin is a host-cell enzyme in various human organs, such as the liver, the lungs, and the small intestines. The fact that this enzyme resides in all of these human tissues means that the virus can potentially attack several organs at once.
SARS-CoV and coronaviruses in the same family do not have the same furin activation site, some studies have shown.
The “furin-like cleavage site” recently discovered in SARS-CoV-2 spike proteins may explain the viral life cycle and pathogenicity of the virus, say researchers.
Prof. Gary Whittaker, a virologist at Cornell University, in Ithaca, New York, also examined the spike protein of the novel coronavirus in a new paper, which is awaiting peer review.
“[The furin activation site] sets the virus up very differently to SARS, in terms of its entry into cells, and possibly affects virus stability and hence transmission.”
– Prof. Gary Whittaker
Other studies have seconded the idea that the furin cleavage site is what makes SARS-CoV-2 transmit so efficiently and rapidly.
Researchers have drawn parallels between SARS-CoV-2 and the avian influenza viruses, noting that a protein called haemagglutinin in influenza is the equivalent of the SARS-CoV-2 spike protein and that furin activation sites may make these viruses so highly pathogenic.
Key receptor on human cells
Spike proteins and furin activation sites are not the whole story, however: The human cell also contains elements that make it vulnerable to the new coronavirus…
Toward new drugs and vaccines…
COVID-19: the biology of an effective therapy
We already know lots about coronavirus biology.
John Timmer, ARS Technica
A coronavirus vaccine may not arrive for at least a year—so what are the chances of finding a useful therapy that could stave off the worst effects of the virus in the meantime?
Earlier coronavirus outbreaks like SARS and MERS raised warning flags for public health officials. Fortunately, they also alerted the biological research community that this large family of viruses was worth studying in more detail. Recent research has built on a large body of knowledge about coronaviruses that have long caused significant diseases in livestock, and so SARS-CoV-2 does not arrive as a total unknown. Indeed, we are actually in a decent position to understand what might make a good potential therapy.
While some of the therapies being tested may seem random—we're trying chloroquine, an antimalarial drug?—there's serious biology behind what's being done.
Genes without DNA
A basic challenge confronts all viral therapies: most viruses have just a handful of genes, and they rely on proteins in the cells they infect (host cells) to perform many of the functions needed to reproduce. But therapies that target host cell proteins run the risk of killing uninfected cells, making matters worse. So antiviral therapies usually target something unique about the virus—something important enough that a few mutations in the virus won't make the therapy ineffective.
Those of you who didn't sleep through high school biology may remember that genetic information is carried by DNA. When a protein needs to be built, the relevant bit of DNA is read and the cell makes a temporary copy of the information using a very similar chemical called RNA. This piece of RNA is then translated into a sequence of amino acids, which form the protein. While there are some exceptions to this—many RNAs perform important functions without ever being translated into proteins—all RNA in our cells is made by transcribing a DNA sequence.
But we've known for a long time that this process doesn't hold for viruses. Many viruses, including HIV and the influenza virus, use RNA for their basic genetic material. The coronavirus is also an RNA virus; it consists of a single, 30,000-base-long RNA molecule.
This is a problem for the virus. The host cells it infects only have proteins that copy DNA, not RNA, so how can more copies of the virus get made?
Target: reproduction ...
Target: processing ...
Target: packaging ...
Target: the viral shell ...
A different approach to antibodies ...
Target: new infections ...
Beyond the obvious ...
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Hundreds of Scientists Scramble to Find a Coronavirus Treatment
In an ambitious international collaboration, researchers have “mapped” proteins in the coronavirus and identified 50 drugs to test against it.
By Carl Zimmer, The New York Times
March 17, 2020
Working at a breakneck pace, a team of hundreds of scientists has identified 50 drugs that may be effective treatments for people infected with the coronavirus.
Many scientists are seeking drugs that attack the virus itself. But the Quantitative Biosciences Institute Coronavirus Research Group, based at the University of California, San Francisco, is testing an unusual new approach.
The researchers are looking for drugs that shield proteins in our own cells that the coronavirus depends on to thrive and reproduce.
Many of the candidate drugs are already approved to treat diseases, such as cancer, that would seem to have nothing to do with Covid-19, the illness caused by the coronavirus.
Scientists at Mount Sinai Hospital in New York and at the Pasteur Institute in Paris have already begun to test the drugs against the coronavirus growing in their labs. The far-flung research group is preparing to release its findings at the end of the week.
There is no antiviral drug proven to be effective against the virus. When people get infected, the best that doctors can offer is supportive care — the patient is getting enough oxygen, managing fever and using a ventilator to push air into the lungs, if needed — to give the immune system time to fight the infection.
If the research effort succeeds, it will be a significant scientific achievement: an antiviral identified in just months to treat a virus that no one knew existed until January.
“I’m really impressed at the speed and the scale at which they’re moving,” said John Young, the global head of infectious diseases at Roche Pharma Research and Early Development, which is collaborating on some of the work.
“We think this approach has real potential,” he said.
Some researchers at the Q.B.I. began studying the coronavirus in January. But last month, the threat became more imminent: A woman in California was found to be infected although she had not recently traveled outside the country.
That finding suggested that the virus was already circulating in the community.
“I got to the lab and said we’ve got to drop everything else,” recalled Nevan Krogan, director of the Quantitative Biosciences Institute. “Everybody has got to work around the clock on this.”
Dr. Krogan and his colleagues set about...
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