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In Oregon, Scientists Discover a Virus Variant With a Worrying Mutation

In Oregon, Scientists Find a Virus Variant With a Worrying Mutation

Scientists in Oregon have discovered a native version of a fast-spreading variant of the coronavirus that first appeared in the UK – but now combined with a mutation that may make the variant less susceptible to vaccines.

The researchers have only found a single case of this formidable combination to date, but genetic analysis revealed that the variant was community-acquired and did not occur in the patient.

“We didn’t import this from anywhere else in the world – it happened spontaneously,” said Brian O’Roak, a geneticist at Oregon Health and Science University who led the work. He and his colleagues participate in the Centers for Disease Control and Prevention efforts to track variants and have posted their results in databases shared by scientists.

The variant originally identified in the UK, named B.1.1.7, has quickly spread throughout the United States, accounting for at least 2,500 cases in 46 states. This form of the virus is both more contagious and deadly than the original version and is expected to be responsible for most infections in America in a few weeks.

The new version, which surfaced in Oregon, shares the same backbone, but also has a mutation – E484K or “Eek” – seen in variants of the virus circulating in South Africa, Brazil and New York City.

Laboratory studies and clinical studies in South Africa show that the Eek mutation makes current vaccines less effective by weakening the body’s immune response. (The vaccines are still working, but the results are worrying enough that Pfizer-BioNTech and Moderna have started testing new versions of their vaccines to defeat the variant found in South Africa.)

The B.1.1.7 variant with Eek has also appeared in the UK and has been described by scientists as a “worrying variant”. But the virus identified in Oregon appears to have evolved independently, said Dr. O’Roak.

Dr. O’Roak and colleagues found the variant among coronavirus samples collected by the Oregon State Public Health Lab across the state, including some from a health care outbreak. Of the 13 test results they analyzed, 10 turned out to be B.1.1.7 alone and one as a combination.

Other experts said the discovery wasn’t surprising given that the Eek mutation appeared in forms of the virus around the world. However, the occurrence of the mutation in B.1.1.7 is worth seeing, they said.

In the UK, this version of the variant makes up a small number of cases. By the time the combination developed there, B.1.1.7 had already spread across the country.

Updated

March 6, 2021, 10:48 p.m. ET

“We’re at the point where B.1.1.7 is just rolling out in the US,” said Stacia Wyman, a computational genomics expert at the University of California at Berkeley. “As it evolves and slowly becomes the dominant thing, it could accumulate more mutations.”

Viral mutations can reinforce or weaken each other. For example, the variants identified in South Africa and Brazil contain many of the same mutations, including Eek. But the Brazilian version has a mutation, K417N, that is not present in the South African version.

What you need to know about the vaccine rollout

In a study published Thursday in Nature, the researchers compared antibody responses with all three affected variants – those identified in the UK, South Africa and Brazil. In line with other studies, they found that the variant that beat South Africa was the most resistant to antibodies produced by the immune system.

But the variant circulating in Brazil was not as resistant, despite carrying the Eek mutation. “If you have the second mutation, you don’t see such a bad effect,” said Michael Diamond, a viral immunologist at Washington University in St. Louis who led the study.

It is too early to say whether the Oregon variant will behave like it did in South Africa or Brazil. But the idea that other mutations might weaken Eek’s effects is “excellent news,” said Dr. Wyman.

Overall, she said, the finding in Oregon reinforces the need for people to continue taking precautions, such as wearing a mask, until a significant portion of the population is vaccinated.

“People don’t have to freak out, they just have to be vigilant,” she said. “We cannot give up our vigilance as long as these more transferrable variants are still in circulation.”

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Russia’s Sputnik vaccine is luring Jap Europe, worrying the EU

Russia’s Sputnik vaccine is luring Eastern Europe, worrying the EU

A medical worker holds a syringe with the Gam-COVID-Vac (Sputnik V) Covid-19 vaccine in his hand.

Alexander Reka | TASS | Getty Images

While the European Union struggles to push coronavirus vaccine rollout in the block of 27, Russia’s Covid shot is proving enticing to its friends in Eastern Europe, creating yet another potential rift in the region.

The Czech Republic, Austria, Hungary and Slovakia have all expressed an interest in the procurement and use of the Russian vaccine “Sputnik V”, which could undermine an EU-wide approach to the approval and administration of coronavirus vaccines.

Czech Prime Minister Andrej Babis said on Sunday that his country could use the Sputnik V vaccine without the approval of the EU Medicines Agency, the European Medicines Agency.

It comes after Russian President Vladimir Putin and Austrian Chancellor Sebastian Kurz received a call last Friday in which they discussed “possible deliveries of the Russian Sputnik-V vaccine to Austria and its possible joint production,” the Kremlin said and found that Austria had initiated the call. Austria has so far stated that it would not bypass the EMA when approving the vaccine.

Hungary, a country within the EU that has close ties to Brussels and whose leader Viktor Orban is considered a close ally of Putin, has shown no such hesitation. It was the first European country to bypass the EMA to approve and purchase the Sputnik V vaccine in January.

According to the Moscow Times, the country expects 2 million doses of the Sputnik V vaccine to be administered over the next three months. Hungary also approved China’s Sinopharm vaccine last month, which again goes against the grain when it comes to EU vaccine approval.

On Monday, Slovakia became the second European country to announce that it had purchased the Sputnik V vaccine, which secured 2 million doses of the shot. However, the Slovak Minister of Health said it will not be given immediately as it still needs the green light from the country’s national drug regulator.

A Slovak Army plane carrying doses of the Sputnik V vaccine against the coronavirus (Covid-19) stands on the tarmac when it arrives from Moscow at Kosice International Airport, Slovakia, on March 1, 2021.

PETER LAZAR | AFP | Getty Images

What’s happening?

The linchpin for the Russian vaccine is widespread frustration with the slow adoption of EU vaccines. The bloc’s decision to jointly buy vaccines has hampered it, and its orders came later than in other countries, including the UK and US

Manufacturing problems and bureaucracy – and hesitation in some countries about vaccines – were also stumbling blocks to adoption.

Nonetheless, the move by some Eastern European countries to unilaterally support Russia’s vaccine will exacerbate problems in Brussels as it undermines the EU’s desire for a unified approach and a sense of equity in the distribution of vaccines.

There were also concerns specifically about Sputnik V, although subsequent data have confirmed the vaccine’s effectiveness and credibility.

The vaccine was approved by the Russian health authority in August last year, ahead of the completion of clinical trials, causing skepticism among experts that it may not meet strict safety and efficacy standards. Some experts argued that the Kremlin is keen to win the race to develop a Covid vaccine.

However, an interim analysis of the Phase 3 clinical trials with 20 participants published in The Lancet in early February found the vaccine to be 91.6% effective against symptomatic Covid-19 infections.

In a companion article in the Lancet, Ian Jones, Professor of Virology at the University of Reading, England noted that “the development of the Sputnik V vaccine has been criticized for undue urgency. However, the result reported here is clear and scientific. The principle of vaccination is demonstrated which means another vaccine can now join the fight to reduce the incidence of Covid-19. “

However, the Gamaleya National Center for Epidemiology and Microbiology in Moscow, which developed the vaccine, has not yet submitted an application to the EMA for marketing authorization for the vaccine, the EU Medicines Agency said in early February.

A woman receives the second component of the Gam-COVID-Vac (Sputnik V) COVID-19 vaccine.

Valentin Sprinchak | TASS | Getty Images

RDIF, Russia’s sovereign wealth fund that backed the development of Sputnik V, announced to CNBC on Monday that it had requested the EU Drugs Agency for an ongoing vaccine review in mid-February. However, the EMA has not confirmed this and CNBC has asked the EMA for a comment.

Political theater

The European Commission already warned Hungary, albeit indirectly, against the use of the Russian vaccine before the EMA approved it. As early as November, a spokesman for the Commission told Reuters: “The question is whether a Member State would like to give its citizens a vaccine that has not been tested by the EMA.” Public confidence in vaccination could be damaged.

“This is where the approval process and confidence in vaccines meet. When our citizens start questioning the safety of a vaccine, it will be much more difficult to get a sufficient proportion of vaccines if it has not undergone rigorous scientific evaluation. to demonstrate its safety and effectiveness to the population, “said the spokesman, reported Reuters.

However, the decision of Hungary to proceed alone with the vaccine against Sputnik V does not surprise the EU observers. The country’s right-wing leader, Viktor Orban – a “strong man” like Russia’s Putin – has had several disputes with the EU executive in recent years, particularly over signs of the government’s increasing authoritarianism. The erosion of the independence of the judiciary and freedom of the press in Hungary is of particular concern to the EU. However, the Hungarian government rejects such criticism.

Gustav Gressel, Senior Policy Fellow at the European Council on Foreign Relations, told CNBC on Monday that Hungary’s actions were “part of Orban’s campaign to promote a” decadent, declining EU “and the future of Hungary in the east with Russia and China.” said it had been going on for some time.

Daragh McDowell, head of Europe and chief analyst for Russia at Verisk Maplecroft, described the geopolitics surrounding Sputnik V and the EU as “political theater more than anything”.

“For Hungary and Austria there is an element of foreign policy signaling here, as both Kurz and Orban generally had a closer relationship with Putin than their European counterparts. In the case of the Czech Republic, the impetus seems to have been more towards the government “Take action” in the face of a rapid surge in the number of cases in February, “he said.

There are also doubts as to whether Russia will be able to mass-produce and ship its Sputnik V vaccine to Europe.

“While the Sputnik vaccine appears to be an effective vaccine in principle, Russia is having great difficulty getting mass production right … enough Sputnik vaccine is still not being made,” Gressel said. McDowell noted that “the question is whether Sputnik V can make a noticeable difference, given regulatory issues and existing logistical issues, and whether the vaccine can be made in sufficient numbers either by Russian manufacturers or under license.”

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The Coronavirus Is a Grasp of Mixing Its Genome, Worrying Scientists

The Coronavirus Is a Master of Mixing Its Genome, Worrying Scientists

In the past few weeks, scientists have been raising the alarm about new variants of the coronavirus that carry a handful of tiny mutations, some of which appear to make vaccines less effective.

But it’s not just these small genetic changes that are cause for concern. The novel coronavirus tends to mix up large chunks of its genome when making copies of itself. Unlike small mutations, which are like typos in sequence, a phenomenon called recombination is similar to a large copy-and-paste mistake, where the second half of a sentence is completely overwritten with a slightly different version.

A number of new studies suggest that recombination can allow the virus to transform itself in dangerous ways. In the long run, however, this biological machinery could provide a silver lining in helping researchers find drugs that will stop the virus.

“There’s no question that recombination is taking place,” said Nels Elde, an evolutionary geneticist at the University of Utah. “And in fact, it’s probably a little underrated and could even play a role in creating some of the new worrying variants.”

The coronavirus mutations that most people have heard of, like the one in the B.1.351 variant first discovered in South Africa, are changes in a single “letter” of the virus or RNA’s long genetic sequence. Because the virus has a robust system for proofreading its RNA code, these small mutations are relatively rare.

In contrast, recombination is widespread in coronaviruses.

Researchers at Vanderbilt University Medical Center, led by virologist Mark Denison, recently looked at how replication goes wrong in three coronaviruses, including SARS-CoV-2, which causes Covid. The team found all three viruses showed “extensive” recombination when replicated separately in the laboratory.

Scientists fear that recombination could combine different variants of the coronavirus into more dangerous versions in a person’s body. For example, variant B.1.1.7, first discovered in Great Britain, had more than a dozen mutations that appeared suddenly.

Dr. Elde said the recombination may have brought together mutations from different variants that may have arisen spontaneously within the same person over time or that co-infected someone at the same time. At the moment this idea is speculative: “It’s really hard to see these invisible scars from a recombination event.” And while it is possible to get infected with two variants at the same time, this is considered rare.

Katrina Lythgoe, an evolutionary epidemiologist at the Oxford Big Data Institute in the UK, is skeptical that co-infection is common. “But the new worrying variants have taught us that rare events can still have a big impact,” she added.

Recombination may also allow two different coronaviruses from the same taxonomic group to exchange some of their genes. To investigate this risk more closely, Dr. Elde and his colleagues tracked the genetic sequences of many different coronaviruses, including SARS-CoV-2 and some of its distant relatives that are known to infect pigs and cattle.

Using specially developed software, the scientists highlighted the places where the sequences of these viruses aligned and matched – and where they did not. The software suggested that in the last few centuries of virus evolution, many of the recombination events involved segments that made up the spike protein that helps the virus enter human cells. This is worrying, the scientists said, because it could be one way that one virus essentially infects another virus.

“Through this recombination, a virus that cannot infect humans could recombine with a virus like SARS-CoV-2 and take over the sequence for the tip and infect people,” said Stephen Goldstein, an evolutionary virologist who worked on the study.

Updated

Apr. 5, 2021, 8:13 p.m. ET

The results, which were posted online on Thursday but not yet published in a scientific journal, provided new evidence that related coronaviruses are quite promiscuous in terms of recombining with one another. There were also many sequences that appeared in the coronaviruses that seemed to come out of nowhere.

“In some cases, it almost looks like a sequence is coming from space, from coronaviruses that we don’t even know about,” said Dr. Elde. The recombination of coronaviruses across completely different groups has not been studied in detail, also because such experiments may have to be subject to a government review in the USA due to security risks.

Feng Gao, a virologist at Jinan University in Guangzhou, China, said that while the Utah researchers’ new software found unusual sequences in coronaviruses, it does not provide any iron evidence of recombination. It could just be that that’s how they evolved.

“Diversity, no matter how much, doesn’t mean recombination,” said Dr. Gao. “It could well be caused by tremendous diversification during virus development.”

Scientists have limited knowledge of whether new pandemic coronaviruses can arise through recombination, said Vincent Munster, a viral ecologist at the National Institute for Allergies and Infectious Diseases who has been studying coronaviruses for years.

Yet this evidence is growing. In a study published in July and officially published today, Dr. Munster and coworkers suggest that recombination is likely, as both SARS-CoV-2 and the virus behind the original SARS outbreak in 2003 resulted in a version of the spike protein that enables them to skillfully invade human cells. This spike protein binds to a specific entry point in human cells called ACE2. This paper calls for stronger coronavirus surveillance to see if there are others who are using ACE2 and therefore may pose similar threats to humans.

Some scientists are studying recombination machinery not only to ward off the next pandemic, but also to combat it.

For example, Dr. Vanderbilt’s Denison, in his recent study of the recombination of three coronaviruses, found that blocking an enzyme known as nsp14-ExoN in a mouse coronavirus caused a decrease in recombination events. This suggests that the enzyme is critical to the ability of coronaviruses to mix and match their RNA during replication.

Now, Dr. Denison and Sandra Weller, virologist at the University of Connecticut Medical School, asked whether this finding could treat people with Covid.

Certain antiviral drugs, like remdesivir, fight infection by acting as RNA bait that speeds up the viral replication process. But these drugs don’t work as well as some coronaviruses would have hoped. One theory is that the enzyme nsp14-ExoN removes the errors caused by these drugs and thus saves the virus.

Dr. Denison and Dr. Among other things, Weller are looking for drugs that block the activity of nsp14-ExoN and allow remdesivir and other antiviral agents to work more effectively. Dr. Weller compares this approach to cocktail therapies for HIV, which combine molecules that act on different aspects of virus replication. “We need combination therapy for coronavirus,” she said.

Dr. Weller notes that coronaviruses share nsp14-ExoN, so a drug that successfully suppresses it can work against more than just SARS-CoV-2. You and Dr. Denison are still in the early stages of drug discovery and are testing various molecules in cells.

Other scientists see potential in this approach not only to make drugs like remdesivir work better, but also to prevent the virus from correcting one of its replication errors.

“I think it’s a good idea,” said Dr. Goldstein, “because you would drive the virus into what is known as a ‘failure catastrophe’ – basically it would mutate so severely that it is fatal to the virus.”