In the last few weeks, scientists have been making noise about new variants of the coronavirus that carries a handful of tiny snails, some of which seem to make vaccines so effective.
But it’s not just these small genetic changes that are worrying. The novel coronavirus tends to mix large chunks of the genome when copying itself. Unlike small mutations, which are similar to typos in the series, a surprise called repetition resembles a large cop-and-paste error in which the second half of a sentence is completely written down with a draft. slightly different.
A series of new studies suggest that relapse may allow the virus to take shape in dangerous ways. But in the long run, this biological device may offer a silver lining, helping researchers find drugs to stop the virus in its pathways.
“There’s no question that recurrence is happening,” said Nels Elde, an evolutionary geneticist at the University of Utah. “In fact, it’s very likely to be undeveloped and could play even when some of the new variables show concern.”
The mutations of the coronavirus that most people have heard, such as those in the B.1.351 variant first discovered in South Africa, are changes in a single “letter” of a long genetic sequence. virus, or RNA. Because the virus has a robust system for reading its RNA code, these small mutations are very rare.
Coronation, by contrast, is abundant in coronaviruses.
Researchers at Vanderbilt University Medical Center led by virus expert Mark Denison recently studied how horrible cases occur during reproduction in three coronaviruses, including SARS-CoV-2, which causes COVID. The team found that all three viruses showed a “widespread” reactivation when reproducing separately in the laboratory.
Scientists are concerned that replication could allow different versions of the coronavirus to coalesce in more dangerous versions within a human body. For example, the B.1.1.7 variant first detected in Britain, for example, had more than a dozen seemingly abrupt mutations.
Elde said that there may be a recurrence of the unification of mutations from different changes that arose independently within the same person over time or were co-infected with someone at the same time. For now, he said, that view is speculative: “It is very difficult to see these invisible divisions from a re-enactment event. “And while it is possible to get an infection with two strains at the same time, it is considered rare.
Katrina Lythgoe, an evolutionary epidemiologist at the Oxford Big Data Institute in Britain, doubts the co-occurrence of co-infection. “But the new variations of concern have taught us that rare events can still have a significant impact,” she said.
Repetition can also allow two different coronaviruses from the same taxonomic group to alter some of their genes. To examine that risk more closely, Elde and his colleagues compared the genetic sequences of many different coronaviruses, including SARS-CoV-2 and some well-known distant relatives who were taking effects on pigs and cattle.
Using specially developed software, the scientists identified the places where the sequences of these viruses aligned and matched – and where they did not. The software suggested that, over the last two centuries of the evolution of viruses, many of the recurrence events involved segments made by the spike protein, which help the virus enter cells. human. That’s sad, scientists said, because it could be a pathway through which one virus actually equips another to capture humans.
“Through this reassignment, a virus that cannot infect humans with a virus such as SARS-CoV-2 and could take the series for a spike, and could infect people,” said Stephen Goldstein, an evolutionary pathologist who worked on the study.
The findings, which were posted online Thursday but not yet published in a scientific journal, offered new evidence that associated coronaviruses are very promising in terms of antagonism. . There were also many strains that emerged in the coronaviruses that seemed to have come out of nowhere.
“In some cases, it looks like a series is falling in from the outside, from coronaviruses that we don’t know about yet,” Elde said. The reintroduction of coronaviruses across completely different groups has not been closely studied, in part because such tests would have to go through a government study in the United States because of safety risks.
Feng Gao, a physiologist at Jinan University in Guangzhou, China, said that although the new software from Utah researchers discovered rare earths in coronaviruses, that does not provide ironclad evidence for reproducibility. It is possible that they were growing like that on their own.
“Diversity, whatever the level, does not mean reconsideration,” Gao said. “It can be caused by massive proliferation during viral evolution.”
Scientists have little information about whether to replace new coronavirus viruses, said Vincent Munster, a viral ecologist with the National Institute for Allergies and Infectious Diseases who has studied coronaviruses for years.
However, that evidence is growing. In a study released in July and formally published today, Munster and his colleagues suggested that there is likely to be recurrence as both SARS-CoV-2 and the virus behind the original SARS revolution in 2003 with a version of the spike protein that allows them to enter human cells efficiently. That spike protein binds to a specific entry point in human cells called ACE2. That paper calls for more research on coronaviruses to see if there are others that use ACE2 and that may pose a risk to humans.
Some scientists are exploring retroviral devices not only to look for the next pandemic, but to help fight this.
For example, in his recent study on the reactivation of three coronaviruses, Denison of Vanderbilt found that an enzyme called nsp14-ExoN in a mouse coronavirus inhibited recombinant events. This suggested that the enzyme is critical to the ability of coronaviruses to mix and match their RNA as they reproduce.
Now, Denison and Sandra Weller, an oncologist at the University of Connecticut School of Medicine, are investigating whether this vision could treat people with COVID.
Some antiviral drugs such as remdesivir fight infections by serving as RNA decoys that stimulate the process of viral reproduction. But these medications do not work as well as some had hoped for coronaviruses. One theory is that the enzyme nsp14-ExoN detects the errors caused by these drugs, thus saving the virus.
Denison and Weller, among others, are looking for drugs that inhibit the activity of nsp14-ExoN, allowing remdesivir and other antivirals to work more like Weller this approach on the therapies cocktail for HIV, which is a combination of molecules that work on different aspects of the virus replication. “We need combination therapy for coronaviruses,” she said.
Weller notes that nsp14-ExoN is shared over coronaviruses, so a drug that has been successfully activated may be resistant to more than just SARS-CoV-2. She and Denison are still at an early stage of drug discovery, testing different molecules in cells.
Other scientists see potential in this approach, not only to make drugs like remdesivir work better, but to prevent the virus from repairing any of the re- his representation.
“I think it’s a good idea,” Goldstein said, “because you would be pushing the virus into what is known as a ‘catastrophic error’ – basically suffocating so much that it is fatal for the virus. ”