New Variants

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trader32176
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New Variants

Post by trader32176 »

We Are Being Told The “Scary” Mutant COVID In South Africa Is Even More Dangerous Than The “Super COVID” In The UK

12/23/20

http://theeconomiccollapseblog.com/we-a ... in-the-uk/


A new mutant strain of COVID-19 that has been dubbed
501.V2” has gotten completely out of control in South Africa, and authorities are telling us that it is an even bigger threat than the “Super COVID” that has been causing so much panic in the United Kingdom. Of course viruses mutate all the time, and so it isn’t a surprise that COVID-19 has been mutating. But mutations can become a major issue when they fundamentally alter the way that a virus affects humans, and we are being told that “501.V2” is much more transmissible than previous versions of COVID and that even young people are catching it a lot more easily. That is potentially a huge concern, because up until now young people have not been hit very hard by the COVID pandemic.

The British press is using the word “scary” to describe this new variant, and at this point it has become the overwhelmingly dominant strain in South Africa…

The new mutant, called 501.V2, was announced in Cape Town last Friday and is believed to be a more extreme variant than Britain’s new Covid strain which has plunged millions into miserable Christmas lockdowns.

Cases in South Africa have soared from fewer than 3,000 a day at the start of December to more than 9,500 per day, with the mutant accounting for up to 90 percent of those new infections.

If this same pattern happens elsewhere as this new mutant strain travels around the globe, then “501.V2” could eventually almost entirely replace all of the older versions of COVID.

Authorities are optimistically telling us that the recent vaccines that have been developed will “likely” work against this new variant, but the truth is that they will not know until testing is done.

And if the vaccines don’t work against “501.V2”, we could be back to square one very rapidly.

For now, countries all over the globe are banning flights from South Africa in a desperate attempt to isolate this new version. The UK, Germany, Switzerland, Turkey and Israel are among the nations that have banned those flights, but so far the United States is not on that list.

So people that are potentially carrying this new version of COVID continue to enter the U.S. on a daily basis.

For the United Kingdom, this flight ban may have come too late because two cases of “501.V2” have already been identified on British soil…

Two cases of a new, “more transmissible” COVID-19 variant linked to South Africa have been identified in the UK, the health secretary has said.

Both cases are contacts of people who travelled from South Africa over the last few weeks, Matt Hancock said at a Downing Street news conference.

If the new vaccines are effective against “501.V2”, authorities believe that they already have the long-term answer to this new variant.

But if those vaccines don’t work, this pandemic could be entering a far more deadly new phase.

And of course we are hearing about more problems with these new vaccines on a daily basis. Thousands of adverse reactions have already been reported to the CDC, and more reports continue to pour in as more people get the shots. Here is one example from New York City…

A health care worker in New York City had a serious adverse reaction to a coronavirus vaccine, officials said on Wednesday.

New York City Health Commissioner David Chokshi said during a news conference that the unidentified worker experienced a “significant allergic reaction” to the vaccine. He added that the worker was treated for the reaction, and is in stable condition and recovering.

We should not be surprised that there are major issues with experimental mRNA vaccines that are based on entirely new technology that were rushed into production without proper testing.

And of course there are tens of millions of Americans that will never take any mRNA vaccine that literally “hijacks your cells” under any circumstances.

On the other hand, most of the U.S. population seems to think that these new vaccines will bring this pandemic to an end, but if they don’t work against new mutant versions of the virus that won’t be true at all.

It is so important to take a balanced view of these things.

Unfortunately, when it comes to COVID most people fall into two camps.

The first camp is totally freaked out because they think that COVID is about the worst thing that could ever happen to the United States and they tend to favor extremely draconian measures to prevent the spread of the virus.

But the truth is that the COVID pandemic pales in comparison to other great pandemics throughout human history. The Black Plague and the Spanish Flu Pandemic each killed at least 50 million people. As for the COVID pandemic, the global death toll has not reached the 2 million mark even if the official numbers are accurate. If a pandemic of this nature is freaking people out so much, what is going to happen when a truly killer plague is unleashed in our society?

The second camp either thinks that the pandemic is greatly exaggerated or that the virus doesn’t even exist at all. Even though hordes of people are catching the virus all around us, many out there continue to deny the reality of this crisis.

I simply do not understand that. So many people that I know around the country have gotten the virus, and that includes quite a few big names. For example, the following is an excerpt from an article in which Daisy Luther shares what her experience with COVID was like…

Days 3-5: Over the next three days, chills and fever were almost constant. My joints and muscles hurt. Getting up to go to the bathroom felt like an expedition up a mountain. I was tired and winded. I had very little appetite and even less of an inclination to cook food so I existed mostly on peanut butter and crackers and leftover soup. I was absolutely exhausted and so cold that I shivered violently when I got out from under my bed piled high with blankets. I had super-weird dreams. My cough worsened, my head hurt, and my throat was still mildly sore.

I drank lots of water and electrolyte beverages. My thirst remained unquenchable regardless of how much I drank. I took vitamins (C, D3) and took Zinc supplements. These are my regular supplements but I doubled that.

Days 6-9: The line to get a test at the local clinic was long and filled with people who were coughing up a lung. There was no way I’d be able to stand in that line for an hour, as sick as I felt. Besides, I figured if I didn’t have Covid, I’d get it standing in the line so I opted not to be tested.

This part made me think of the worst case of the flu I ever had, except intensified by about four times. It was terrible.

I usually let a fever run its course but by Saturday I felt so awful that I gave in and began treating symptoms. My normal temp is in the 96s and my temperature throughout these days stayed between 101-103. I staggered ibuprofen and acetaminophen, and I also used a mild muscle relaxant and my Ventilyn inhaler. The meds didn’t get rid of my fever but reduced the chills to a tolerable level. I slept almost around the clock, waking up for a couple of hours here and there to check on website stuff. Fortunately, I have a wonderful team who kept things running for us. One day blurred into the next and I considered going to the doctor again, but couldn’t muster the energy. I felt like if I just got a little more sleep I’d be okay.

My cough was getting far worse and now my ribs and abdominal muscles hurt. It was a deep painful cough that caused me to clutch my chest every single time inhaled deeply.

So to summarize, yes the COVID pandemic is real, but it is not the end of the world.

More people are going to get sick, and some will suffer intensely, but the vast majority of those that get the virus will survive.

If you want to wear a mask, then wear a mask.

If you don’t want to wear a mask, then don’t wear a mask.

We should be free to make our own choices, and we should also be free to experience the consequences for those choices.

Unfortunately, there are way too many people out there that think that they have the right to censor and control what we say and what we do, and that trend is likely to only get worse as our society continues to spin out of control in the years ahead.
trader32176
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Re: New Variants

Post by trader32176 »

How Fast Can Scientists Find the New Coronavirus Strains?

The discovery of more contagious variants of SARS-CoV-2 in the US sparks a push for a long-overdue national genomic surveillance network.


1/8/21


https://www.wired.com/story/how-fast-ca ... s-strains/


Late last week, Charles Chiu’s lab at UC San Francisco received a shipment of test tubes from the California Department of Public Health. This wasn’t out of the ordinary. For almost a year, Chiu, an infectious disease doctor, has been collaborating with the state agency to conduct genetic sequencing on samples from people who’ve tested positive for the coronavirus that causes Covid-19. Like all viruses, SARS-CoV-2 mutates as it moves through a population. Most of these mutations are trivial and don’t change how the virus behaves. But by making a record of these mutations, scientists can track the coronavirus’s spread and better understand the origins of different outbreaks.

Chiu had been assisting with this kind of genetic detective work for months. This time, though, he had reason to think his team was about to find something new.

Two of the samples belonged to members of a household in Big Bear, California, who got sick after one of them had contact with a traveler who had recently returned from the United Kingdom. And during standard diagnostic testing, something strange had happened to both samples. The test detected bits of a protein that protects the virus’s genome, but not the spike protein SARS-CoV-2 uses to invade cells. That meant that whatever strain had infected these people had probably acquired at least one mutation in the virus’s spike protein gene. Mutations in that location are one signature of the new, seemingly more contagious variety of the coronavirus that has been rapidly spreading in the UK and now around the world.

By Saturday, Chiu’s lab had sequencing results. And sure enough, those two samples turned up 23 telltale mutations in the spike protein. Both people had been infected with the UK variant, known as B.1.1.7. At the time, there were fewer than 10 such cases in the US, following an initial discovery of the UK variant in Colorado on December 29. As of January 8, at least 52 people have been confirmed to have contracted the new strain, according to data from the Centers for Disease Control and Prevention. So far, it has shown up in New York, Florida, and Georgia, in addition to California and Colorado.

Chiu thinks the real picture is actually far worse. “I suspect it’s circulating in nearly every state in the US,” he says. “It’s just that other states don’t have the same sequencing capabilities.”

Since the beginning of the pandemic, coronavirus sequencing has been a patchy, ad hoc affair, dominated by areas with big biomedical research institutions that are staffed by scientists eager to investigate the virus’s evolution. States like California and Colorado are sequencing and uploading hundreds of viral genomes every week, according to the latest data from an international virus-sharing database known as GISAID. But others have only done a few dozen—total. North Dakota, which for the month of November held the ignominious record for the worst outbreak in the US, has yet to sequence a single sample. On a national level, the US simply hasn’t built out a robust, coordinated, genomic surveillance system capable of keeping tabs on problematic new mutations wherever they might arise. The result is not just scarce sequencing. It’s a monitoring system missing huge chunks of the country.

“We are really behind in terms of having geographically representative data,” says Kelly Wroblewski, the director of infectious disease for the Association of Public Health Laboratories. She sees the failure as the inevitable outcome of the Trump administration’s decision to leave nearly every aspect of the coronavirus response up to individual states—from ramping up diagnostic testing to rolling out vaccines. “There was no national sequencing plan, because there has not been a national much-of-anything plan,” she says.

Of the more than 21.5 million Covid-19 cases officially reported in the US, samples from just 59,438 people, or less than 0.3 percent, have been sequenced and analyzed for variants, according to GISAID. By contrast, the UK is regularly sequencing more than 10 percent of its Covid-19 cases. That allowed British public health officials to monitor in real time as the B.1.1.7 variant went from being a rare find at the beginning of December to dominating new infections three weeks later. The Brits might be an outstanding example in this regard, but they’re not alone. According to a recent Washington Post analysis, 42 other countries have sequenced more cases than the US, despite the fact that Americans account for a quarter of all coronavirus infections globally.

“What the US is doing right now is completely inadequate,” says Chiu. He thinks American government officials should be setting their sights on that 10 percent threshold. But the effort will undoubtedly be complicated by the fractured US health care system. In the UK, which has a single nationalized health service and a supporting microbiology service, it’s relatively easy to flow samples and data. In the US, the private sector still dominates the testing market. In order for a sample to show up in Chiu’s lab, he says, it has to go from a commercial lab to the county lab and then to the state lab before it gets to him. That can take weeks—if it even happens at all. Often, by the time a public health department epidemiologist comes across a case they want to investigate with genetics, the original sample has already been discarded. “The rate-limiting step isn’t sequencing; it’s really getting the sample,” says Chiu. “That’s why we have to empower state and county labs to do it in-house, so we can get the data out faster.”

Over the last decade, public health labs have built up their sequencing capacities as part of their role in tracking outbreaks of foodborne illness across the US. Every state lab, as well as a handful of large regional ones, has the technology readily available, according to Wrobleski. But they haven’t been able to deploy it widely during the pandemic because they’ve had their hands full just trying to conduct basic diagnostic tests and contact tracing, she says. And until a few weeks ago, they hadn’t been given marching orders to do anything differently.

But that’s finally starting to change.

In mid-December, the CDC released $15 million to public health labs around the country to boost sequencing outputs nationwide. That was part of a multipronged effort now underway at the agency to increase both the number of coronavirus variants being characterized and the locations from which they’re being drawn. The money will help states participate in a dedicated SARS-CoV-2 Strain Surveillance program, dubbed NS3, which the CDC launched in November. When the program is fully operational, public health labs will be expected to send 10 randomly selected coronavirus samples to the CDC’s labs in Atlanta every other week. The samples should represent patients from different age, racial, and ethnic groups, as well as the geographic diversity of each state. In addition to sequencing them, CDC scientists will also use the samples to build up a centralized strain library that they can dip into to perform additional tests.

“Sequencing will tell us a lot, but it can’t tell us everything,” says Gregory Armstrong, who leads the CDC’s Office of Advanced Molecular Detection. For example, one of the things public health experts are concerned about is how well people with existing immunity gained through a previous bout with Covid-19 will be able to fend off infections with this new UK strain. To test it, scientists have to be able to assess how well the antibodies found in the blood of Covid-19 survivors attack and neutralize the B.1.1.7 version of the virus. Another alarming possibility is that the vaccines that have been developed and authorized so far won’t be as effective against emerging strains. “We need to have a library of variants in order to get those answers,” says Armstrong.

The NS3 program, which Armstrong expects to be fully up and running by the end of the month, will help with that. But it won’t get the US as much genetic data as public health officials need to track the progress of B.1.1.7 and other emerging strains, like an alarming one that originated in South Africa, through the American populace. That’s why the CDC is also bringing large commercial testing labs on board. In December, the agency signed contracts with LabCorp and Illumina, and it is in the process of negotiating further deals with others that have the capacity to acquire and sequence samples from all around the country. In addition, since September the CDC has granted about $8 million to academic sequencing centers and is currently seeking to bring additional sites online. Data from all these efforts is continuously analyzed by CDC scientists and uploaded to public databases like GISAID for other researchers to use.

These new efforts are designed to boost the efforts of scientists like Chiu, who since the early stages of the pandemic has been part of a CDC-led coalition of more than 160 research institutions, non-governmental organizations, and public health agencies called Spheres (Sequencing for Public Health Emergency Response, Epidemiology, and Surveillance). The federal initiative aims to help scientists agree on data and quality standards, but it doesn’t foot the bill for actual lab work. And it hasn’t been able to keep pace with the pandemic.

“We feel very strongly that we haven’t been sequencing enough,” says Armstrong. “That’s why we’re taking these steps right now to scale things up.” In December, labs throughout the US were sequencing about 3,000 viral genomes per week. He’s optimistic that by combining the forces of public, academic, and commercial labs, the nation can get up to 6,500 viral genomes per week by the end of January.

Wrobleski speculates that the newfound urgency at the CDC comes from a collision of forces—the surfacing of more transmissible, and possibly more dangerous, new strains right as the beleaguered public health agency wriggles free of the political meddling of the Trump administration. Whatever the reason, the window to get it right is closing, says Chiu. “The point of doing surveillance is to find these rare variants and, in doing so, make sure they continue to be rare. If we do it now, we can hopefully still prevent these variants from blowing up and becoming the predominant lineage. That would be a disaster.”
trader32176
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Re: New Variants

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Global coronavirus cases surpass 90 million in battle on new variant

1/10/21


https://www.reuters.com/article/health- ... SKBN29G0GB


(Reuters) - Worldwide coronavirus cases surpassed 90 million on Monday, according to Reuters tally, as nations around the globe scramble to procure vaccines and continue to extend or reinstate lockdowns to fight new coronavirus variants.

The new COVID-19 variants discovered initially in the United Kingdom and South Africa are rapidly spreading globally.

The novel coronavirus has picked up pace in the past few months with about one-third of total cases registered in the last 48 days, according to a Reuters tally.

Europe, which became the first region to report 25 million cases last week, remains the worst-affected area in the world, followed by North and Latin Americas with 22.4 million and 16.3 million cases respectively.

Europe has reported around 31% of about 1.93 million coronavirus-related deaths globally.

The United Kingdom, the worst-affected European country, crossed 3 million cases last Friday.

The nation is on course to have immunized its most vulnerable people against COVID-19 by mid-February and plans to offer a shot to every adult by autumn.

To control the spread of new coronavirus variant, countries across the globe have started to extend movement and business restrictions.

In Germany, Chancellor Angela Merkel and state premiers last week agreed to restrict non-essential travel for residents of hard-hit areas all over Germany for the first time, after a lockdown decreed in December failed to significantly reduce infection numbers.

French authorities imposed a stricter evening curfew in Marseille after authorities said the new variant of the COVID-19 virus initially found in the UK had been discovered in the Mediterranean city.

The United States, world’s worst affected country, reported its highest death toll on Wednesday, with over 4,000 fatalities in a single day.

The nation has recorded more than 22 million cases since the pandemic started, reporting on average 245,000 new infections a day over the last seven days, according to a Reuters analysis.

In Asia, India crossed 150,000 deaths last Tuesday, becoming the third nation to reach the grim milestone.

The south Asian nation has approved two COVID-19 vaccines and will start its vaccination drive from Jan. 16 with priority given to about 30 million healthcare and frontline workers.
trader32176
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Re: New Variants

Post by trader32176 »

Another new coronavirus variant found in Japan

1/11/21


https://www.japantimes.co.jp/news/2021/ ... ant-japan/


A new coronavirus variant has been detected in four travelers from Brazil’s Amazonas state, Japan’s health ministry said Sunday. The strain differs from highly infectious variants first found in Britain and South Africa that have driven a surge in cases in those countries.

A ministry official said studies were underway into the efficacy of vaccines against the new variant.

“At the moment, there is no proof showing the new variant found in those from Brazil is high in infectiousness,” Takaji Wakita, head of the National Institute of Infectious Diseases (NIID), told a health ministry briefing.

Still, Brazil’s Health Ministry said it has been notified by Japanese authorities that the new variant has 12 mutations, one of which is also present in the variants found in the U.K. and South Africa. “It implies a potential higher virus infectiousness,” it said.

Of the four travelers who arrived at Tokyo’s Haneda Airport on Jan. 2, a man in his 40s had a problem breathing, a woman in her 30s had a headache and sore throat and a teenage male had a fever, while a teenage girl showed no symptoms, the health ministry said.

The four people tested positive for the novel coronavirus in airport quarantine, and the new mutant strain was detected through a detailed examination by the NIID, according to the ministry.

The ministry also said that the variant reported in Britain has been found in three different people who had close contact with a man infected with the strain.

Brazil’s Health Ministry asked the Japanese government to provide information on the new variant of the novel coronavirus detected in the four travelers.

The ministry asked for information such as the genetic sequence of the new strain.

The Brazilian ministry has taken necessary preventive measures including sending a cautionary notice to related domestic organizations, an official said.

It has asked the Japanese ministry about information on the travelers’ stays in Brazil in order to track their possible contact with others, the official said.

Brazil is experiencing a second wave of coronavirus infections, with a daily average of more than 50,000 people testing positive for the virus in January. In Brazil, the mutant strains of the British and South African types have been confirmed.

In Japan, the government declared a state of emergency for Tokyo and three neighboring prefectures last week after seeing a steep rise in coronavirus cases,.

Cumulative cases nationwide have reached about 289,000, with 4,067 deaths as of Sunday, public broadcaster NHK said.
trader32176
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Re: New Variants

Post by trader32176 »

Will the Pfizer–BioNTech vaccine be effective against the new N501Y SARS-CoV-2 variant?

1/12/21


https://www.news-medical.net/news/20210 ... riant.aspx


While the coronavirus disease 2019 (COVID-19) pandemic continues to wreak havoc in many parts of the world, a new variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged.

This new variant, called N501Y, has caused skyrocketing cases in the UK, where it first emerged in September 2020. To date, the country has reported more than 3.12 million cases and over 82,000 deaths.

The rise of this highly infectious new strain has raised serious questions about whether or not the current vaccine candidates will be effective in immunizing against it. It has also brought a new urgency to the vaccination effort in the UK and elsewhere where roll-outs have begun.

Researchers from Pfizer and the University of Texas, USA, have presented evidence showing that people in a previously reported trial of the mRNA-based COVID-19 vaccine, BNT162b2 – commonly known as the Pfizer-BioNTech COVID-19 vaccine – had equivalent neutralizing titers to the N501 and Y501 viruses, suggesting that the vaccine could be effective against this new strain. The team's findings have been published on the preprint bioRxiv* server.

Fast spreading SARS-CoV-2 variant


Emerging in September, a new strain of SARS-CoV-2 has recently exploded across southeast England, prompting the government to impose stringent restrictions and lockdown orders in what is now a third national lockdown since the pandemic first begun. The new variant is highly transmissible and fast-spreading.

The new variant contains 23 mutations, 8 of which are in the spike proteins, the part of the virus that binds human cells and facilitates its entry. The novel mutations include the N501Y mutation that allows the virus to bind more tightly to the angiotensin-converting enzyme 2 (ACE2) receptor. It also contains the D614G deletion, which has been observed to spread more rapidly between people than earlier strains.

In an investigation of the new strain conducted by Public Health England, researchers have noted that the N501Y shows significantly higher transmissibility than previous strains, though have not found any evidence to suggest it is more lethal or virulent.

The study

In the study, the researchers generated isogenic N501 and Y501 SARS-CoV-2. Blood samples of participants in a previously reported trial of the BNT162b2 vaccine showed equivalent neutralizing titers to the new variants.

To arrive at the study findings, the researchers obtained the blood samples from the participants that were obtained 2 or 4 weeks after immunization with two 30- µg doses of BNT162b2 spaced three weeks apart. The blood samples were tested for neutralization assay.

The results showed that the ratio of the 50 percent neutralization geometric mean titers (GMTs) of the blood samples against the Y501 virus to that against the N501 virus was 1.46. This means that there was no reduction in the neutralization activity against the SARS-CoV-2 that contains the Y501 spike.

Nevertheless, preserved neutralization of Y501 virus by BNT162b2-elicited human sera is consistent with preserved neutralization of a panel of 15 pseudoviruses bearing spikes with other mutations found in circulating SARS-CoV-2 strains,” the researchers concluded in the study.

The Pfizer-BioNtech vaccine has demonstrated a 95 percent efficacy in protecting against COVID-19 in its human trials, which involved at least 44,000 participants who are 16 years of age or older. The results present evidence that the vaccine could potentially target even the novel variants, which have caused surging cases in some countries, particularly in the UK and South Africa.

Since SARS-CoV-2 is a novel virus, it is expected to evolve, leading to the emergence of new variants. The ongoing evolution of the virus requires persistent monitoring of the significance of changes to ensure vaccine coverage. Many scientists have emphasized the importance of preparing for future mutations of the virus, which may necessitate a vaccine strain change.

A previous study has also noted that it is better to target fast-spreading strains of the virus to reduce the initial ballooning of cases.

To date, there are nearly 91 million confirmed COVID-19 cases. Of these, 1.94 million have died from the infection. The United States reports the highest number of cases, reaching 22.61 million; followed by India, with 10.47 million cases; Brazil, with about 8.13 million cases; and Russia, with over 3.41 million cases. The virus has now reached 191 countries and regions across the globe.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Sources:

COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU) - https://gisanddata.maps.arcgis.com/apps ... 7b48e9ecf6
Investigation of novel SARS-COV-2 variant. Variant of Concern 202012/01. Public Health England - https://assets.publishing.service.gov.u ... L2_SH2.pdf

Journal reference:

Xie, X., Zou, J., Fontes-Garfias, C., et al. (2021). Neutralization of N501Y mutant SARS-CoV-2 by BNT162b2 vaccine-elicited sera. bioRxiv. doi: https://doi.org/10.1101/2021.01.07.425740, https://www.biorxiv.org/content/10.1101 ... 7.425740v1
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Re: New Variants

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Effect of mutations in the South African SARS-CoV-2 variant on transmission and neutralization

1/12/21


https://www.news-medical.net/news/20210 ... ation.aspx


The transmissibility of the novel coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is high, while most infections appear to be very mild or asymptomatic. This has led to a pandemic of coronavirus disease 2019 (COVID-19) that has currently claimed over 1.96 million lives within one year. Scientists have come up with many vaccines at varying points of development. However, new variants of the virus continue to emerge, some of which are alleged to be even more transmissible or may possibly evade neutralization by the antibodies induced by newly approved vaccines.

One such strain is the South African 501.V2 and UK B1.1.7 strains, which have been isolated from many countries and seem to spread faster than the ancestral strain. A preprint that recently appeared on the bioRxiv* server reports the computational structure of this strain and the possible effect of the mutations on infectivity and neutralization.

The aim of the study

SARS-CoV-2 depends on its trimeric spike glycoprotein to achieve infection. The spike monomer is composed of two subunits, S1 and S2, with the receptor-binding domain (RBD) being located on the former. This region recognizes and binds to the host cell receptor, the angiotensin-converting enzyme 2 (ACE2). The S2 subunit mediates cell fusion and the internalization of the virus, after two cleavage steps catalyzed by host proteases, which cause a substantial change in protein conformation.

Most monoclonal antibodies and vaccines against SARS-CoV-2 at present are directed against the spike RBD. However, the UK variant has eight mutations in the spike, while the 501.V2 has three, both including N501Y in the RBD. The current study aims to understand the effect of the three mutations in the latter strain on RBD-ACE2 binding and neutralization by monoclonal antibodies targeting the spike. The researchers used molecular modeling and simulations to understand the structure of the mutant spike protein.

N501Y increases ACE2 binding affinity


The researchers found that the N501 residue forms two hydrogen bonds with two ACE2 residues that stabilize the RBD-ACE2 complex. When mutated to 501Y, three additional bonds are formed with residues like Y41 and K353, which increase the affinity. These residues have been established to be crucial to ACE2 binding with the SARS-CoV spike. Thus, the mutation is expected to enhance ACE2 affinity and thus promote transmission.

K417N and E484K reduce binding affinity


However, the accompanying K417N and E484K mutations in the South African strain provide a counterpoise to the spike's increased affinity due to the N501Y mutation. They prevent the formation of two salt bridges that help to form and stabilize the RBD-ACE2 complex. This reduces ACE2 binding affinity. Thus, this strain is less infectious and less rapidly spreading than the UK strain. This is even though both share the latter substitution.

Neutralizing antibodies mostly unaffected by triple mutation

Secondly, the researchers demonstrated that five of the eleven monoclonal antibodies that were structurally analyzed for binding to the mutant and ancestral strains do not have significant contacts at the mutation sites. Alternatively, they show additional interactions at such sites that compensate for any lack of affinity. This suggests that with most antibodies, including one of the two Regeneron monoclonals in their antibody cocktail, they continue to be at least as effective against the mutant strains as against the wildtype virus. With two others, namely, with the monoclonal antibodies B38 and 2-4, efficacy is increased up to twofold, as new favorable interactions occur between the residues.

With others like C105 and H11-14, the perturbed interactions at the binding interface due to the mutations K417N and/or E484K are too significant to be completely reversed by conformational rearrangement. For instance, with the former, the network of interactions that is formed via the K147 residue is abolished by the mutation at this site. However, new interactions is formed at this site and by 501Y, with other residues, but overall, binding affinity is reduced.

Weaker positive interactions, or even repulsions at some sites, are also observed with three other antibodies, including the other Regeneron antibody. This indicates that this variant could have a 2-4 weaker affinity for binding by these antibodies and thus escape neutralization.

The researchers also found that both N501 and K417 play an essential part in the dynamics of the RBD-ACE2 complex, as mechanical hinge centers or as regulatory sites.

What are the implications?

The study made use of already accumulated structural data on various ACE2-RBD or spike RBD-antibody complexes to predict the effects of various substitutions and deletions on binding affinity. They conclude, “Despite the stronger binding to ACE2 caused by the substitution N501Y, the South African 501.V2 variant that has undergone two additional mutations (K417N and E484K) is unlikely to exhibit an increased infectivity and likely transmissibility.”

When it comes to antibody escape, the effects were mixed. Either combinations of antibodies that target distinct non-overlapping epitopes or use different neutralization mechanisms should be developed to prevent mutational escape. In view of the availability of mutational maps, it is necessary to develop monoclonal antibodies that have binding sites with high resistance to viral escape. This could mean positioning epitopes outside the RBD or using epitopes shared by both SARS-CoV and SARS-CoV-2 since these do not typically tolerate mutation. The researchers say they recently identified such an antibody targeting the putative SARS-CoV-2 spike superantigenic-like motif. This is the antibody 6D3, which not only blocks the S1/S2 cleavage site, but also blocks the superantigenic site that may cause severe systemic inflammation in advanced COVID-19.

The study brings out the utility of computational predictions, which can be tested to understand the dose of an antibody required to overcome such mutations. With both therapeutic monoclonal antibodies and new viral variants being on the rise, “this type of in silico assisted genomic/molecular surveillance may provide feedback for accelerating the design of experimental studies in response to the pandemic.”

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:


Cheng, M. H. et al. (2021). Impact of South African 501.V2 Variant on SARS-CoV-2 Spike Infectivity and Neutralization: A Structure-based Computational Assessment. bioRxiv preprint doi: https://doi.org/10.1101/2021.01.10.426143. https://www.biorxiv.org/content/10.1101 ... 0.426143v1
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Re: New Variants

Post by trader32176 »

New technology could protect against different coronavirus variants

1/13/21


https://www.news-medical.net/news/20210 ... iants.aspx


The SARS-CoV-2 virus that is causing the COVID-19 pandemic is just one of many different viruses in the coronavirus family.

Many of these are circulating in populations of animals like bats and have the potential to "jump" into the human population, just as SARS-CoV-2 did. Researchers in the laboratory of Pamela Björkman, the David Baltimore Professor of Biology and Bioengineering, are working on developing vaccines for a wide range of related coronaviruses, with the aim of preventing future pandemics.

Now, led by graduate student Alex Cohen, a Caltech team has designed a protein-based 60-subunit nanoparticle onto which pieces of up to eight different types of coronavirus have been attached.

When injected into mice, this vaccine induces the production of antibodies that react to a variety of different coronaviruses--including similar viruses that were not presented on the nanoparticle.

The research is described in a paper in the journal Science.

This vaccine platform, called a mosaic nanoparticle, was developed initially by collaborators at the University of Oxford. The nanoparticle is shaped like a cage made up of 60 identical proteins, each of which has a small protein tag that functions as a piece of Velcro.

Cohen and his team took fragments of the spike proteins of different coronaviruses (spike proteins play the biggest role in infection) and engineered each to have a protein tag that would bind to those on the cage--the other half of the piece of Velcro.

When these viral pieces were mixed together with the nanoparticle cage structure, each virus tag stuck to a tag on the cage, resulting in a nanoparticle presenting spikes representing different coronavirus strains on its surface.

Displaying eight different coronavirus spike fragments (known as receptor binding domains or RBDs) with this particle platform generated a diverse antibody response, which is an advantage over traditional vaccine methods that present pieces from only a single type of virus.

After inoculation, the antibodies subsequently produced by mice were able to react to many different strains of coronavirus. Importantly, the antibodies were reactive to related strains of coronavirus that were not present on the nanoparticle.

This suggests that, by presenting the immune system with multiple different coronavirus variants, the immune system learns to recognize common features of coronaviruses and thus could potentially react to a newly emerging coronavirus--not just a SARS-CoV-2 variant--that might cause another pandemic.

Although the team is still studying the mechanism underlying this phenomenon, the results are promising. The next step is to examine whether immunization prevents viral infection and/or infection symptoms in animals making these antibodies.


" If we can show that the immune response induced by our nanoparticle technology indeed protects against the illness resulting from infection, then we hope that we could move this technology forward into human clinical trials, though there are a lot of steps that need to happen between now and then."

- Alex Cohen, Graduate Studdent, California Institute of Technology

"We don't envision that this methodology would replace any existing vaccines, but it's good to have many tools on hand when facing future emerging viral threats."

"Unfortunately SARS-CoV-2 is unlikely to be the last coronavirus to cause a pandemic," says Björkman. "Alex's results show that it is possible to raise diverse neutralizing antibody responses, even against coronavirus strains that were not represented on the injected nanoparticle. So we are hopeful that this technology could be used to protect against future animal coronaviruses that cross into humans. In addition, the nanoparticles elicit neutralizing responses against SARS-CoV-2, so it could be possible to use them now to protect against COVID-19 as well as other coronaviruses with pandemic potential."

Source:

California Institute of Technology

Journal reference:

Cohen, A. A., et al. (2021) Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice. Science. doi.org/10.1126/science.abf6840.
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Re: New Variants

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How Scientists Trace New Coronavirus Variants

1/13/21





NPR's Ailsa Chang talks with biologists Pardis Sabeti and Sharon Peacock about how genomic sequencing was used in the U.K. to trace a new coronavirus variant and what the U.S. can learn from it.

AILSA CHANG, HOST:

A new variant of the coronavirus has now been found in at least 10 states. The strain, known as B117, is thought to be more contagious. And U.K. scientists first alerted the world about it in December. In the meantime, we have heard reports of other additional variants found in South Africa and in Japan. So what does this say about the coronavirus' ability to evolve and our ability to fight it?

Well, I have a couple of virus detectives with me now. Pardis Sabeti is a computational biologist at the Broad Institute in Massachusetts, and Sharon Peacock is the director of the COVID-19 Genomics U.K. Consortium. Welcome to both of you.

PARDIS SABETI: It's a pleasure to be here.

SHARON PEACOCK: Thank you very much.

CHANG: So Dr. Peacock, let's just start with you. You know, it was your team that helped track down this new COVID variant. Can you just explain - how did you first figure out that you found something new?

PEACOCK: Well, there are many, many mutations in the viral population. And what you need to do is look for a signal in people for some different viral behavior. And so in December, what we noticed was that there were numbers of cases of COVID-19 in people in the south of England.

Now, they were under lockdown restrictions. And strangely, in other parts of the country, that same lockdown was controlling the disease very well. But in the south of England, it wasn't managing to control spread of the infection. And so at that point during the investigation - the outbreak investigation - it became very apparent this was associated with this new variant, which contained a large number of mutations, which we hadn't seen before. And that's what really set it off.

CHANG: OK. And how different, exactly, is this strain - B117 - from the initial strain sequenced in China at the very beginning of the pandemic? Like, how different both genetically and how different in the way the two viruses interact with us as human hosts?

PEACOCK: This virus is actually strikingly different, and it has 23 different mutations. And what concerns us is that some of those mutations are in part of the virus called the spike protein, which is the protein that interacts with humans and attaches to human cells and is part of the entry process into the body. And so this is actually very unusual. But in particular, it has mutations that could change the biology - the way that the virus interacts with humans.

CHANG: Well, OK. Dr. Sabeti, along with the U.K. variant, scientists have found other significant variants in South Africa and in Japan. Is that all that surprising to you or were scientists expecting this to happen as we got deeper and deeper into the pandemic?

SABETI: You know, these are viruses, and like everything on Earth, they change over time. But viruses, in particular, they're replicating and spreading quickly, and they have high mutation rates compared to us. Just the way that their biological machinery works is they're making more changes each time they replicate. So this is expected. We saw during the Ebola outbreak, during the previous SARS outbreaks, during every outbreak, you know, that happens, viruses are mutating all the time. That's what we expect.

CHANG: So can tracking these sorts of variants help us curb the spread of the virus in some way?

SABETI: It can. And, you know, I think it's very important to do - as the U.K. did - is to be able to scan at high resolution in real time, or near real time. Because if you do identify something like the B117 mutation, and you notice, hey, there's something going on in this part of the country and oh, there's this new variant to pay attention to, we can scan for where that variant is occurring and try to then move our public health resources, which are inherently limited, but to take all the resources we can to stop that variant from going anywhere.

CHANG: Well, given that this U.K. strain appears to be more contagious, let me ask both of you this question. Does our current public health guidance around social distancing and mask wearing, does that need to change?

PEACOCK: There's no reason to think that standard advice about infection prevention and control needs to change. So we still need to wash our hands, wear masks and distant - socially distance. And so it is more contagious, but there's every reason to think that if we follow the guidance, that disease transmission can be reduced and prevented.

CHANG: And Dr. Sabeti?

SABETI: Yeah. I think that the guidelines that we have in place are very good. And they work for most viruses - you know, washing hands and social distancing, wearing masks. The more contagious a virus, the more it means we have to be really regimented about that. And any breaches at all, and you could have mass containment failure. And so it just makes us have to really ante up on those.

CHANG: So, you know, this strain, as we keep saying, was first detected in the U.K. So let me ask you, Dr. Sabeti - how equipped do you think the U.S. is to detect these kinds of genetic changes in the virus moving forward?

SABETI: The U.S. is very equipped to detect these kinds of mutations, and they have been doing across the board. The difference between the U.K. and the U.S. in this instance is the U.K., on a national level, really put down a lot of funds and support and made this a priority whereas - I'll say that my colleagues and I here in the U.S., most of this work is done on our discretionary funds, on very limited budgets. And so we're very poised and doing a lot of great and exciting sequencing across the U.S., but not at the level and the scale that's needed. And so we've been calling for some time - for many, many years - to have national funding to scale this up. We're poised and able to do it. Literally, it's just about getting more sequences through the pipeline, which is more funding and support and prioritization of the need.

CHANG: So as this pandemic continues to drag on, what else will you be watching for? Like, are you going to be expecting more strains to emerge?

PEACOCK: I think it's very likely that we'll see new variants emerge. And what we're really watching for are variants that actually are transmissible, but that actually have the ability to escape immunity. So that's either the immunity that's acquired naturally if you have COVID-19 once or immunity that's developed through vaccination. So in particular, looking for combinations of mutations that could allow a virus to be very fit and spread amongst the population, but that could also threaten the efficacy of vaccines.

The other thing we worry about is mutations that could affect the way that diagnostic tests can work. So some mutations can affect the ability of a diagnostic test to detect the virus. So also looking out for those types of mutations.

CHANG: That is Sharon Peacock, director of the COVID-19 Genomics U.K. Consortium, and Pardis Sabeti of the Broad Institute. Thank you to both of you.

PEACOCK: Thank you.

SABETI: Thank you.
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Re: New Variants

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New 'Columbus strain' of coronavirus evolved in the US

The variant has three gene mutations that haven't previously been seen together.

1/13/21


https://www.livescience.com/us-covid-19 ... -ohio.html


Two new COVID-19 variants have been found in Ohio, and they appear to have originated in the United States, researchers announced on Wednesday (Jan. 13).

One of these variants, dubbed the "Columbus strain," has three gene mutations that haven't previously been seen together in SARS-CoV-2, the virus that causes COVID-19, according to a statement from The Ohio State University Wexner Medical Center. These mutations occur in the so-called spike protein of the virus, which it uses to latch onto cells.

This strain quickly became the dominant coronavirus variant in Columbus, Ohio, over a three-week period from late December 2020 to early January, according to the researchers, who hope to post their findings soon on the pre-print database bioRxiv.

"This new Columbus strain has the same genetic backbone as earlier cases we've studied, but these three mutations represent a significant evolution," study leader Dr. Dan Jones, vice chair of the division of molecular pathology at they Wexner Medical Center, said in the statement. "We know this shift didn't come from the U.K. or South African branches of the virus."

The Ohio researchers have been regularly sequencing the SARS-CoV-2 genome from patient samples since March 2020 to monitor the virus's evolution.

Like other coronavirus variants found around the world, including the U.K. variant, the mutations in the Columbus strain occur in the virus's "spike protein," which allows the virus to enter cells. It's possible these mutations make the virus more transmissible, the researchers said.

But so far, there is no evidence that these mutations would impact the effectiveness of COVID-19 vaccines, according to the researchers.

"It's important that we don't overreact to this new variant until we obtain additional data," said Peter Mohler, a co-author of the study and chief scientific officer at the Wexner Medical Center

The second variant found by the Ohio researchers has a mutation dubbed 501Y that is identical to one seen in the U.K. variant. This mutation affects the receptor-binding domain, or part of the virus's spike protein that latches onto the ACE2 receptor in human cells; in lab-dish experiments, the mutated receptor-binding domain binds more tightly to the ACE2 receptor, past research found.

But the researchers believe the Ohio variant independently evolved that mutation from a strain already in the U.S. It was found in one patient from Ohio, so the researchers don't yet know how prevalent it is in the population overall.

A spokesperson for the Centers for Disease Control and Prevention told CNBC that the agency is reviewing the new research.
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