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SARS-Arena reveals hidden hooks in virus

HOUSTON – (July 13, 2022) – Vaccines may need to dig a little deeper to stop SARS-CoV-2. Rice University researchers are providing a new shovel. Credit:…

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HOUSTON – (July 13, 2022) – Vaccines may need to dig a little deeper to stop SARS-CoV-2. Rice University researchers are providing a new shovel.

Credit: Illustration by Mauricio Menegatti Rigo/Rice University

HOUSTON – (July 13, 2022) – Vaccines may need to dig a little deeper to stop SARS-CoV-2. Rice University researchers are providing a new shovel.

The lab of computer scientist Lydia Kavraki at Rice’s George R. Brown School of Engineering has introduced a program to look for conserved parts of proteins of the virus that causes COVID-19. These parts could help develop future vaccines. 

The lab’s open-source program, SARS-Arena, identifies peptides that are part of the virus’s nucleocapsid protein to see how they could be targeted. Kavraki said the program was designed from the outset to be highly customizable and easy to use. 

“Our work does not analyze the surface spike proteins of SARS-related coronaviruses but a protein deep inside the core of such viruses,” Kavraki said. “We define and systematize a complex process of discovering fragments of that protein that can serve as a basis for the development of novel vaccines.” 

Details about SARS-Arena appear in Frontiers in Immunology. The program itself can be found here: https://github.com/KavrakiLab/SARS-Arena.

The program builds upon the lab’s established HLA-Arena, a customizable pipeline for structural modeling and analysis of complexes formed by peptides – small parts of proteins – and human leukocyte antigen (HLA) receptors, central to the cellular immunity. 

SARS-CoV-2 nucleocapsid protein is compact and hidden within the SARS shell, where it helps in viral genome packaging. The protein is highly conserved across SARS viruses, and because it is located in the inner part of the virus, it is also less subject to mutation than proteins along the surface envelope, especially the spike protein targeted by most current COVID vaccines.

Surface proteins are a moving target for vaccines, said lead author and postdoctoral researcher Mauricio Menegatti Rigo. The omicron variant has more than 30 mutations in the spike protein alone, and that has probably contributed to its rapid infection rate. 

Nucleocapsid proteins are highly expressed upon infection. That also increases opportunities for the immune system to spot them and move in. Nucleocapsids are highly immunogenic, making them likely to provoke an immune response. 

But not all of the well-conserved peptide “hooks” within the nucleocapsid are known, nor is there sufficient data on how they bind to HLAs. Identifying more of them could aid the search for broad-spectrum, long-lasting coronavirusvaccines, Rigo said.

“We are mostly interested in the cellular immune response triggered against nucleocapsid peptides,” he said. “So the first part of the paper is about identifying these conserved peptides. In the second part, we provide a way to analyze not only the sequence of the peptides but also how they could bind to HLA molecules.

“Then we can look for clues about how the peptides are presented in the context of the immune response,” Rigo said. “We show that through structural analysis, we can identify cross-reactive peptides and also similar peptides that are potentially cross-reactive. These similar peptides that are not described in the literature are putative new targets for vaccines.”

There are studies showing that immune-system T-cells taken from recovered COVID-19 patients can recognize multiple regions of the nucleocapsid protein, providing long-term protective immunity. So finding peptide targets within the nucleocapsid became a worthy goal, Rigo said. 

The new work is a continuation of efforts by the Rice team to simplify the search for coronavirus vaccines. In a November 2020 paper published in the Proceedings of the National Academy of Sciences, the researchers identified a SARS-CoV-2 peptide that affects binding stability with an immune system receptor, influencing a body’s ability to attack diseased cells. Another paper published in June by Nature’s Scientific Reports improves upon their algorithm to predict binding affinity between peptide structures and HLAs. That study has implications for the development of both virus and cancer vaccines. 

Rice alumnus Dinler Amaral Antunes, now an assistant professor of computational biology at the University of Houston, is co-corresponding author of the paper. Co-authors are Rice graduate students Romanos Fasoulis, Anja Conev and Sarah Hall-Swan. Kavraki is the Noah Harding Professor of Computer Science and a professor of bioengineering, mechanical engineering and electrical and computer engineering, and director of the Ken Kennedy Institute.

The National Science Foundation (2033262), the Cancer Prevention and Research Institute of Texas (RP170593), a National Library of Medicine Training Program fellowship (T15LM007093-29) and the National Institutes of Health (U01CA258512) supported the research.

-30-

Read the abstract at https://www.frontiersin.org/articles/10.3389/fimmu.2022.931155/abstract.

DOI: www.doi.org/10.3389/fimmu.2022.931155.

This news release can be found online at https://news.rice.edu/news/2022/sars-arena-reveals-hidden-hooks-virus.

Follow Rice News and Media Relations via Twitter @RiceUNews.

Related materials:

Rice web server helps identify COVID-19 drug candidates: https://news.rice.edu/news/2021/rice-web-server-helps-identify-covid-19-drug-candidates

Once-discounted binding mechanism may be key to targeting viruses: https://news.rice.edu/news/2020/once-discounted-binding-mechanism-may-be-key-targeting-viruses

SARS-Arena: https://github.com/KavrakiLab/SARS-Arena

Kavraki Lab: https://www.kavrakilab.org

Department of Computer Science: https://csweb.rice.edu

George R. Brown School of Engineering: https://engineering.rice.edu

Images for download:

https://news-network.rice.edu/news/files/2022/07/0718_ARENA-1-WEB.jpg

Rice University computer scientists have developed SARS-Arena to help find conserved parts in proteins from SARS-CoV-2 that could be a key for the development of wide-spectrum vaccines. The program searches for potential matches between regions in nucleocapsid (N) proteins and human leukocyte antigen (HLA) receptors that are central to cellular immunity. (Credit: Illustration by Mauricio Menegatti Rigo/Rice University)

https://news-network.rice.edu/news/files/2022/07/0718_ARENA-2-WEB.jpg

Rice University graduate students, from left, Anja Conev, Romanos Fasoulis and Sarah Hall-Swan and postdoctoral researcher Mauricio Menegatti Rigo worked on the development of SARS-Arena, a program that helps find conserved parts in proteins from SARS-CoV-2 that could be a key for the development of wide-spectrum vaccines. (Credit: Rice University)

Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation’s top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 4,240 undergraduates and 3,972 graduate students, Rice’s undergraduate student-to-faculty ratio is just under 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is ranked No. 1 for lots of race/class interaction and No. 1 for quality of life by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger’s Personal Finance.

 

 

 

 


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Survey Shows Declining Concerns Among Americans About COVID-19

Survey Shows Declining Concerns Among Americans About COVID-19

A new survey reveals that only 20% of Americans view covid-19 as "a major threat"…

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Survey Shows Declining Concerns Among Americans About COVID-19

A new survey reveals that only 20% of Americans view covid-19 as "a major threat" to the health of the US population - a sharp decline from a high of 67% in July 2020.

(SARMDY/Shutterstock)

What's more, the Pew Research Center survey conducted from Feb. 7 to Feb. 11 showed that just 10% of Americans are concerned that they will  catch the disease and require hospitalization.

"This data represents a low ebb of public concern about the virus that reached its height in the summer and fall of 2020, when as many as two-thirds of Americans viewed COVID-19 as a major threat to public health," reads the report, which was published March 7.

According to the survey, half of the participants understand the significance of researchers and healthcare providers in understanding and treating long COVID - however 27% of participants consider this issue less important, while 22% of Americans are unaware of long COVID.

What's more, while Democrats were far more worried than Republicans in the past, that gap has narrowed significantly.

"In the pandemic’s first year, Democrats were routinely about 40 points more likely than Republicans to view the coronavirus as a major threat to the health of the U.S. population. This gap has waned as overall levels of concern have fallen," reads the report.

More via the Epoch Times;

The survey found that three in ten Democrats under 50 have received an updated COVID-19 vaccine, compared with 66 percent of Democrats ages 65 and older.

Moreover, 66 percent of Democrats ages 65 and older have received the updated COVID-19 vaccine, while only 24 percent of Republicans ages 65 and older have done so.

“This 42-point partisan gap is much wider now than at other points since the start of the outbreak. For instance, in August 2021, 93 percent of older Democrats and 78 percent of older Republicans said they had received all the shots needed to be fully vaccinated (a 15-point gap),” it noted.

COVID-19 No Longer an Emergency

The U.S. Centers for Disease Control and Prevention (CDC) recently issued its updated recommendations for the virus, which no longer require people to stay home for five days after testing positive for COVID-19.

The updated guidance recommends that people who contracted a respiratory virus stay home, and they can resume normal activities when their symptoms improve overall and their fever subsides for 24 hours without medication.

“We still must use the commonsense solutions we know work to protect ourselves and others from serious illness from respiratory viruses, this includes vaccination, treatment, and staying home when we get sick,” CDC director Dr. Mandy Cohen said in a statement.

The CDC said that while the virus remains a threat, it is now less likely to cause severe illness because of widespread immunity and improved tools to prevent and treat the disease.

Importantly, states and countries that have already adjusted recommended isolation times have not seen increased hospitalizations or deaths related to COVID-19,” it stated.

The federal government suspended its free at-home COVID-19 test program on March 8, according to a website set up by the government, following a decrease in COVID-19-related hospitalizations.

According to the CDC, hospitalization rates for COVID-19 and influenza diseases remain “elevated” but are decreasing in some parts of the United States.

Tyler Durden Sun, 03/10/2024 - 22:45

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Rand Paul Teases Senate GOP Leader Run – Musk Says “I Would Support”

Rand Paul Teases Senate GOP Leader Run – Musk Says "I Would Support"

Republican Kentucky Senator Rand Paul on Friday hinted that he may jump…

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Rand Paul Teases Senate GOP Leader Run - Musk Says "I Would Support"

Republican Kentucky Senator Rand Paul on Friday hinted that he may jump into the race to become the next Senate GOP leader, and Elon Musk was quick to support the idea. Republicans must find a successor for periodically malfunctioning Mitch McConnell, who recently announced he'll step down in November, though intending to keep his Senate seat until his term ends in January 2027, when he'd be within weeks of turning 86. 

So far, the announced field consists of two quintessential establishment types: John Cornyn of Texas and John Thune of South Dakota. While John Barrasso's name had been thrown around as one of "The Three Johns" considered top contenders, the Wyoming senator on Tuesday said he'll instead seek the number two slot as party whip. 

Paul used X to tease his potential bid for the position which -- if the GOP takes back the upper chamber in November -- could graduate from Minority Leader to Majority Leader. He started by telling his 5.1 million followers he'd had lots of people asking him about his interest in running...

...then followed up with a poll in which he predictably annihilated Cornyn and Thune, taking a 96% share as of Friday night, with the other two below 2% each. 

Elon Musk was quick to back the idea of Paul as GOP leader, while daring Cornyn and Thune to follow Paul's lead by throwing their names out for consideration by the Twitter-verse X-verse. 

Paul has been a stalwart opponent of security-state mass surveillance, foreign interventionism -- to include shoveling billions of dollars into the proxy war in Ukraine -- and out-of-control spending in general. He demonstrated the latter passion on the Senate floor this week as he ridiculed the latest kick-the-can spending package:   

In February, Paul used Senate rules to force his colleagues into a grueling Super Bowl weekend of votes, as he worked to derail a $95 billion foreign aid bill. "I think we should stay here as long as it takes,” said Paul. “If it takes a week or a month, I’ll force them to stay here to discuss why they think the border of Ukraine is more important than the US border.”

Don't expect a Majority Leader Paul to ditch the filibuster -- he's been a hardy user of the legislative delay tactic. In 2013, he spoke for 13 hours to fight the nomination of John Brennan as CIA director. In 2015, he orated for 10-and-a-half-hours to oppose extension of the Patriot Act

Rand Paul amid his 10 1/2 hour filibuster in 2015

Among the general public, Paul is probably best known as Capitol Hill's chief tormentor of Dr. Anthony Fauci, who was director of the National Institute of Allergy and Infectious Disease during the Covid-19 pandemic. Paul says the evidence indicates the virus emerged from China's Wuhan Institute of Virology. He's accused Fauci and other members of the US government public health apparatus of evading questions about their funding of the Chinese lab's "gain of function" research, which takes natural viruses and morphs them into something more dangerous. Paul has pointedly said that Fauci committed perjury in congressional hearings and that he belongs in jail "without question."   

Musk is neither the only nor the first noteworthy figure to back Paul for party leader. Just hours after McConnell announced his upcoming step-down from leadership, independent 2024 presidential candidate Robert F. Kennedy, Jr voiced his support: 

In a testament to the extent to which the establishment recoils at the libertarian-minded Paul, mainstream media outlets -- which have been quick to report on other developments in the majority leader race -- pretended not to notice that Paul had signaled his interest in the job. More than 24 hours after Paul's test-the-waters tweet-fest began, not a single major outlet had brought it to the attention of their audience. 

That may be his strongest endorsement yet. 

Tyler Durden Sun, 03/10/2024 - 20:25

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The Great Replacement Loophole: Illegal Immigrants Score 5-Year Work Benefit While “Waiting” For Deporation, Asylum

The Great Replacement Loophole: Illegal Immigrants Score 5-Year Work Benefit While "Waiting" For Deporation, Asylum

Over the past several…

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The Great Replacement Loophole: Illegal Immigrants Score 5-Year Work Benefit While "Waiting" For Deporation, Asylum

Over the past several months we've pointed out that there has  been zero job creation for native-born workers since the summer of 2018...

... and that since Joe Biden was sworn into office, most of the post-pandemic job gains the administration continuously brags about have gone foreign-born (read immigrants, mostly illegal ones) workers.

And while the left might find this data almost as verboten as FBI crime statistics - as it directly supports the so-called "great replacement theory" we're not supposed to discuss - it also coincides with record numbers of illegal crossings into the United States under Biden.

In short, the Biden administration opened the floodgates, 10 million illegal immigrants poured into the country, and most of the post-pandemic "jobs recovery" went to foreign-born workers, of which illegal immigrants represent the largest chunk.

Asylum seekers from Venezuela await work permits on June 28, 2023 (via the Chicago Tribune)

'But Tyler, illegal immigrants can't possibly work in the United States whilst awaiting their asylum hearings,' one might hear from the peanut gallery. On the contrary: ever since Biden reversed a key aspect of Trump's labor policies, all illegal immigrants - even those awaiting deportation proceedings - have been given carte blanche to work while awaiting said proceedings for up to five years...

... something which even Elon Musk was shocked to learn.

Which leads us to another question: recall that the primary concern for the Biden admin for much of 2022 and 2023 was soaring prices, i.e., relentless inflation in general, and rising wages in particular, which in turn prompted even Goldman to admit two years ago that the diabolical wage-price spiral had been unleashed in the US (diabolical, because nothing absent a major economic shock, read recession or depression, can short-circuit it once it is in place).

Well, there is one other thing that can break the wage-price spiral loop: a flood of ultra-cheap illegal immigrant workers. But don't take our word for it: here is Fed Chair Jerome Powell himself during his February 60 Minutes interview:

PELLEY: Why was immigration important?

POWELL: Because, you know, immigrants come in, and they tend to work at a rate that is at or above that for non-immigrants. Immigrants who come to the country tend to be in the workforce at a slightly higher level than native Americans do. But that's largely because of the age difference. They tend to skew younger.

PELLEY: Why is immigration so important to the economy?

POWELL: Well, first of all, immigration policy is not the Fed's job. The immigration policy of the United States is really important and really much under discussion right now, and that's none of our business. We don't set immigration policy. We don't comment on it.

I will say, over time, though, the U.S. economy has benefited from immigration. And, frankly, just in the last, year a big part of the story of the labor market coming back into better balance is immigration returning to levels that were more typical of the pre-pandemic era.

PELLEY: The country needed the workers.

POWELL: It did. And so, that's what's been happening.

Translation: Immigrants work hard, and Americans are lazy. But much more importantly, since illegal immigrants will work for any pay, and since Biden's Department of Homeland Security, via its Citizenship and Immigration Services Agency, has made it so illegal immigrants can work in the US perfectly legally for up to 5 years (if not more), one can argue that the flood of illegals through the southern border has been the primary reason why inflation - or rather mostly wage inflation, that all too critical component of the wage-price spiral  - has moderated in in the past year, when the US labor market suddenly found itself flooded with millions of perfectly eligible workers, who just also happen to be illegal immigrants and thus have zero wage bargaining options.

None of this is to suggest that the relentless flood of immigrants into the US is not also driven by voting and census concerns - something Elon Musk has been pounding the table on in recent weeks, and has gone so far to call it "the biggest corruption of American democracy in the 21st century", but in retrospect, one can also argue that the only modest success the Biden admin has had in the past year - namely bringing inflation down from a torrid 9% annual rate to "only" 3% - has also been due to the millions of illegals he's imported into the country.

We would be remiss if we didn't also note that this so often carries catastrophic short-term consequences for the social fabric of the country (the Laken Riley fiasco being only the latest example), not to mention the far more dire long-term consequences for the future of the US - chief among them the trillions of dollars in debt the US will need to incur to pay for all those new illegal immigrants Democrat voters and low-paid workers. This is on top of the labor revolution that will kick in once AI leads to mass layoffs among high-paying, white-collar jobs, after which all those newly laid off native-born workers hoping to trade down to lower paying (if available) jobs will discover that hardened criminals from Honduras or Guatemala have already taken them, all thanks to Joe Biden.

Tyler Durden Sun, 03/10/2024 - 19:15

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