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Post by Admin on Apr 17, 2020 19:09:10 GMT
 The mysterious patient samples arrived at Wuhan Institute of Virology at 7 P.M. on December 30, 2019. Moments later, Shi Zhengli’s cell phone rang. It was her boss, the institute’s director. The Wuhan Center for Disease Control and Prevention had detected a novel coronavirus in two hospital patients with atypical pneumonia, and it wanted Shi’s renowned laboratory to investigate. If the finding was confirmed, the new pathogen could pose a serious public health threat—because it belonged to the same family of bat-borne viruses as the one that caused severe acute respiratory syndrome (SARS), a disease that plagued 8,100 people and killed nearly 800 of them between 2002 and 2003. “Drop whatever you are doing and deal with it now,” she recalls the director saying. Shi—a virologist who is often called China’s “bat woman” by her colleagues because of her virus-hunting expeditions in bat caves over the past 16 years—walked out of the conference she was attending in Shanghai and hopped on the next train back to Wuhan. “I wondered if [the municipal health authority] got it wrong,” she says. “I had never expected this kind of thing to happen in Wuhan, in central China.” Her studies had shown that the southern, subtropical areas of Guangdong, Guangxi and Yunnan have the greatest risk of coronaviruses jumping to humans from animals—particularly bats, a known reservoir for many viruses. If coronaviruses were the culprit, she remembers thinking, “could they have come from our lab?” While Shi’s team at the Chinese Academy of Sciences institute raced to uncover the identity and origin of the contagion, the mysterious disease spread like wildfire. As of this writing, about 81,000 people in China have been infected. Of that number, 84 percent live in the province of Hubei, of which Wuhan is the capital, and more than 3,100 have died. Outside of China, about 41,000 people across more than 100 countries and territories in all of the continents except Antarctica have caught the new virus, and more than 1,200 have perished. The epidemic is one of the worst to afflict the world in recent decades. Scientists have long warned that the rate of emergence of new infectious diseases is accelerating—especially in developing countries where high densities of people and animals increasingly mingle and move about. “It’s incredibly important to pinpoint the source of infection and the chain of cross-species transmission,” says disease ecologist Peter Daszak, president of EcoHealth Alliance, a New York City–based nonprofit research organization that collaborates with scientists, such as Shi, around the world to discover new viruses in wildlife. An equally important task, he adds, is hunting down other related pathogens—the “known unknowns”—in order to “prevent similar incidents from happening again.” To Shi, her first virus-discovery expedition felt like a vacation. On a breezy, sunny spring day in 2004, she joined an international team of researchers to collect samples from bat colonies in caves near Nanning, the capital of Guangxi. Her inaugural cave was typical of the region: large, rich in limestone columns and—being a popular tourist destination—easily accessible. “It was spellbinding,” Shi recalls, with milky-white stalactites hanging from the ceiling like icicles, glistening with moisture. But the holidaylike atmosphere soon dissipated. Many bats—including several insect-eating species of horseshoe bats that are abundant in southern Asia—roost in deep, narrow caves on steep terrain. Often guided by tips from local villagers, Shi and her colleagues had to hike for hours to potential sites and inch through tight rock crevasses on their stomach. And the flying mammals can be elusive. In one frustrating week, the team explored more than 30 caves and saw only a dozen bats. These expeditions were part of the effort to catch the culprit in the SARS outbreak, the first major epidemic of the 21st century. A Hong Kong team had reported that wildlife traders in Guangdong first caught the SARS coronavirus from civets, mongooselike mammals that are native to tropical and subtropical Asia and Africa. |
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Post by Admin on May 7, 2020 5:11:48 GMT
She is a renowned virologist. She is an expert on coronavirus in bats. She is the supposed director of the Wuhan Institute of Virology. Shi Zhengli may have the answer to the question the world is asking. Did the coronavirus originate in her lab? But Shi Zhengli is missing. This is just one of the many things that's mysterious about her. Shi Zhengli is called China's bat woman. Shi began her studies on bats in 2004. She has studied all kinds of bats. The ones picked from caves. The ones from the subtropical regions in the south. Her research was aimed at understanding the SARS outbreak.  She made a breakthrough in 2013. Shi Zhengli found bat faeces with the virus 96.2 per cent identical to the SARS COV-2. Yes, this is the same virus that caused COVID-19. In 2013, Shi began altering parts of the coronavirus. She wanted to study whether coronavirus can be transmitted from one species to another. In 2015, she concluded that the SARS-like virus can jump from bats to human. On December 30, 2020, Shi received some samples from healthcare workers in Wuhan. The samples were from patients in Wuhan who were showing atypical pneumonia.This was a new coronavirus. The Wuhan coronavirus. By the time Shi Zhengli started analyzing the samples. It was too late. The virus had spread to the rest of China and within months, it had crossed borders. Did this virus escape from Shi's lab? Only Shi has the answer. But she is missing. But on February 2, 2020, the virologist re-appeared online on WeChat. She said- “I promise with my life that the virus has nothing to do with the lab'. A month later, she reportedly admitted to having several sleepless nights. “Could they have come from our lab?” The bat expert was asking herself this question. Soon rumours surfaced on social media. Some claimed she defected to the West. And she took along with her years of confidential research on bat coronavirus. Word was that the Wuhan lab director was taking asylum at the US Embassy in Paris. Shi quashed these rumours. Again, on Wechat. “No matter how difficult things are, it [defecting] shall never happen,” “We’ve done nothing wrong. With a strong belief in science, we will see the day when the clouds disperse and the sun shines.” She also posted nine pictures. Not of her lab, or herself, but evidence of being in Wuhan. Some said the Chinese had muzzled her. This sparked another set of questions.  |
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Post by Admin on May 16, 2020 19:10:45 GMT
 Shi Zhengli’s new paper identifies the Chinese horseshoe bat as the natural host for Sars-related coronaviruses. Shi Zhengli, the Chinese virologist whose work has been the subject of controversial theories about the origin of the novel coronavirus, has published new research into Sars-related pathogens and their animal hosts. The head of the centre for emerging infectious diseases at the Wuhan Institute of Virology, Shi said in a paper published on the preprint website Biorxiv.org on Thursday that the Chinese horseshoe bat was the natural host for Sars-related coronaviruses (SARSr-CoVs). The research, which has not been peer-reviewed, said that the bat carried many coronaviruses with a high degree of genetic diversity, particularly in the spike protein, which suggested they had evolved over time to aid their transmission. “All tested bat SARSr-CoV spike proteins had a higher binding affinity to human ACE2 than to bat ACE2, although they showed a 10-fold lower binding affinity to human ACE2 compared with their SARS-CoV counterpart,” the paper said. The ACE2, or angiotensin-converting enzyme 2, is a protein that provides the entry point for the coronavirus to hook onto and infect human cells, while the spike protein is the part of the virus that binds to human cells. Earlier laboratory research established a strong genetic link between the coronavirus that causes Covid-19 and one found in a horseshoe bat in southeastern China. Shi has been the subject of intense speculation over her work at the institute, which includes the discovery of the natural bat reservoir for the Sars (severe acute respiratory syndrome) pathogen that spread through southern China from 2002 to 2003. US President Donald Trump last month said he had a high degree of confidence that the novel coronavirus was linked to the Wuhan Institute of Virology, even after US intelligence said that while it was “not man-made or genetically modified”, it was still examining information to determine if the outbreak began from infected animals or a lab accident. Shi had weeks earlier denied the pathogen had somehow leaked from her lab. “I guarantee with my life that the virus has nothing to do with my lab,” she said in a WeChat post in February. |
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Post by Admin on Jun 2, 2020 2:19:02 GMT
RNA Those of you who have followed the virus closely, however, may be wondering what's going on here. All of this recombination takes place between DNA molecules. But the coronavirus genome is composed of RNA. So why would any of it work there? The answer is that it doesn't. But other processes essentially perform the same function, mixing up pieces of RNA to form distinct genetic combinations. For example, the influenza virus spreads its genome across eight different molecules, allowing cells infected by more than one strain of flu virus to produce viral particles that have a random assortment of molecules from the two strains. Coronavirus' genome is a single, long RNA molecule, so that sort of recombination doesn't work there. But it still can recombine. The enzyme that copies the RNA genome moves down it from one end to the other, making a copy as it goes. Sometimes, however, it can stall and fall off the molecule it's copying, while still hanging on to its partially complete copy. In many cases, the copying will just be aborted. But in others, it can latch on to a new genome and use the copy to pick up where it left off. Critically, the new molecule with which it restarts the copying doesn't have to be the one it was copying originally. It just has to be similar to the first one it copied—it doesn't have to be identical. As a result, this process can allow recombination among viruses that are relatively distantly related from an evolutionary perspective. All they have to do is infect the same host.  Swapping genes Now that we know recombination can take place, how would we go about looking for it? The key here is that we now have a lot of coronavirus sequences from a lot of different hosts available in public databases. Dedicated public health researchers have even gone in and sampled dozens of bat sources to look for strains that might be capable of starting a pandemic. So, for the new analysis, the research team started with a collection of 43 different coronaviruses from a variety of species, including humans, bats, and the pangolin sequences known to be similar to SARS-CoV-2. The basic genome analysis confirmed that SARS-CoV-2 is most closely related to a number of viruses that had been isolated from bats. But different areas of the virus were more or less related to different bat viruses. In other words, you'd see a long stretch of RNA that's most similar to one virus from bats, but it would then switch suddenly to look most similar to a different bat virus. This sort of pattern is exactly what you'd expect from recombination, where the switch between two different molecules would cause a sudden change in the sequence at the point where the exchange took place. (You'd see this rather than differences from both parent molecules being spread evenly throughout the genome.) Spike protein But there was a notable exception to this mixing of bat viruses: the spike protein that sits on the virus' surface and latches on to human cells. Here, the researchers found exactly what the earlier studies had suggested: a key stretch of the spike protein, the one that determines which proteins on human cells it interacts with, came from a pangolin version of the virus through recombination. In other words, both of the ideas from earlier work were right. SARS-CoV-2 is most closely related to bat viruses and most closely related to pangolin viruses. It just depends on where in the genome you look. The other bit of information to come out of this study is an indication of where changes in the virus' proteins are tolerated. This inability to tolerate changes in an area of the genome tends to be an indication that the protein encoded by that part of the genome has an essential function. The researchers identified a number of these, one of which is the part of the spike protein that came from the pangolin virus. Of all 6,400 of the SARS-CoV-2 genomes isolated during the pandemic, only eight from a single cluster of cases had any changes in this region. So, it's looking likely that the pangolin sequence is essential for the virus' ability to target humans. Worrying evidence There's some good news in all of this: rumors about this being an escaped weapons experiment make little sense in terms of what the genome sequences tell us about biology. Less reassuring, however, is what the sequences tell us about the giant natural experiment that may be going on around us. And that tells us there appears to be a large number of coronaviruses that are regularly exchanging genetic information. And, while exchanges are more common among viruses that infect the same species, it's entirely possible that contributions can come from much more distantly related ones. The authors find evidence that the viruses from different species may experience distinct selective pressure, which isn't really surprising. But that also can produce difficult-to-predict results when those viruses hop to a new species—and the difficulty will rise if they then exchange information with other viruses native to that species. Summing this up, there seem to be myriad coronaviruses out there (including plenty we don't know about), and some species are serving as labs in which new genetic combinations are created. And, right now, we only have a very partial window into the sort of potential out there in species that have frequent contacts with humans. And some research cited by the authors suggests that humans have been exposed to at least some of these viruses (based on antibodies to them)—fortunately without a major outbreak occurring. All of which suggests that additional pandemics are a question of when, rather than if. But, of course, that had already been suggested in the aftermath of MERS and the original SARS, and the world as a whole did remarkably little to study the risk, work towards treatments, or plan for the pandemic's arrival. We can only hope that the more obvious example of COVID-19 will change that. Science Advances, 2019. DOI: 10.1126/sciadv.abb9153 (About DOIs). |
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Post by Admin on Jul 25, 2020 6:23:02 GMT
Scientists have for the first time sequenced the genetic material that codes for bats’ unique adaptations and superpowers, such as the ability to fly, to use sound to move effortlessly in complete darkness, to survive and tolerate deadly diseases, and to resist aging and cancer. The results have been reported by researchers working with the Bat1K consortium, who generated and analyzed six highly accurate bat genomes that they say are ten times more complete than any bat genome published to date.
Among the findings, the researchers identified evolution through gene expansion and loss in a family of genes, APOBEC3, which is known to play an important role in immunity to viruses in other mammals. The new insights could set the groundwork for investigating how these genetic changes—which are found in bats but not in other mammals—could help prevent the worst outcomes of viral diseases in other mammals, including humans.
“Given these exquisite bat genomes, we can now better understand how bats tolerate viruses, slow down aging, and have evolved flight and echolocation,” said Emma Teeling, PhD, University College Dublin, co-founding director of Bat1K and senior author of the team’s published paper in Nature. “These genomes are the tools needed to identify the genetic solutions evolved in bats that ultimately could be harnessed to alleviate human aging and disease.” Bat1K is a global consortium of scientists dedicated to sequencing the genomes of every one of the 1,421 living bat species. Teeling and international colleagues reported their results in a paper titled, “Six reference-quality genomes reveal evolution of bat adaptations,” in which they concluded, “in summary, these genomes are comparable to the best reference-quality genomes that have so far been generated for any eukaryote with a gigabase-sized genome.”
With more than 1,400 species of bat species identified to date, these animals account for more than 20% of all currently living mammal species, the authors wrote. Bat species are found all around the world, and occupy many different ecological niches. “Their global success is attributed to an extraordinary suite of adaptations, including powered flight, laryngeal echolocation, vocal learning, exceptional longevity, and a unique immune system that probably enables bats to better tolerate viruses that are lethal to other mammals (such as severe acute respiratory syndrome-related coronavirus, Middle East respiratory syndrome-related coronavirus, and Ebola virus).”
Bats, therefore, represent an important model system for studying traits such as extended healthspan and enhanced disease tolerance, but in order to understand bat evolution and the molecular basis of these traits, scientists need to be able to analyze high-quality genomes. To generate these exquisite bat genomes, Teeling and colleagues used the newest technologies of the DRESDEN-concept Genome Center, a shared technology resource, to sequence the bats’ DNA, and then generated new methods to assemble the pieces into the correct order, and to identify the genes present. While previous efforts had identified genes with the potential to influence the unique biology of bats, uncovering how gene duplications contributed to this unique biology was complicated by incomplete genomes.
“Using the latest DNA sequencing technologies and new computing methods for such data, we have 96–99% of each bat genome in chromosome level reconstructions—an unprecedented quality akin to for example the current human genome reference which is the result of over a decade of intensive ‘finishing’ efforts,” commented co-senior author Eugene Myers, PhD, director of the Max Planck Institute of Molecular Cell Biology and Genetics, and the Center for Systems Biology. “As such, these bat genomes provide a superb foundation for experimentation and evolutionary studies of bats’ fascinating abilities and physiological properties.”
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