9 months ago

Baudry Lab finds 125 naturally occurring compounds with potential against COVID-19

The Baudry Lab at The University of Alabama in Huntsville (UAH) has identified 125 naturally occurring compounds that have a computational potential for efficacy against the COVID-19 virus from the first batch of 50,000 rapidly assessed by a supercomputer.

It’s the first time a supercomputer has been used to assess the treatment efficacy of naturally occurring compounds against the proteins made by COVID-19. Located in UAH’s Shelby Center for Science and Technology, the lab is searching for potential precursors to drugs that will help combat the global pandemic using the Hewlett Packard Enterprise (HPE) Cray Sentinel supercomputer.

The UAH team is led by molecular biophysicist Dr. Jerome Baudry (pronounced Bō-dre), the Mrs. Pei-Ling Chan Chair in the Department of Biological Sciences. Dr. Baudry is video blogging about his COVID-19 research journey using HPE’s Cray Sentinel system. His research is in collaboration with the National Center for Natural Products Research at the University of Mississippi School of Pharmacy and HPE.

“We have used supercomputers to predict natural products most likely to bind to three proteins of the SARS-CoV-2 virus,” says Dr. Baudry. SARS-CoV-2 is the scientific name for COVID-19.

“Out of the 50,000 natural products that we have looked at using supercomputers, we find several hundred to be predicted to be potentially binding on the proteins of interest,” he says.

“We further found 125 – but there may be more – that are particularly interesting because they bind right where we want to, they are not too big, not too small and they have the chemical profiles of pharmaceuticals.”

There are many diverse natural sources for the chemicals of interest, Dr. Baudry says.

“Many are from relatively common medicinal plants that can be found in the U.S., and many are from more distant plants from Southeast Asia and South America, as well as from some ground and oceanic bacteria strains and fungi.”

Promising compounds will undergo a computational technique called pharmacophore analysis to find what the chemicals have in common and flag chemical features important for future research.

The next phase for the compounds is in vitro testing by a partner laboratory that will use live virus and live cells. Those chemical molecules found most efficacious will form the basis for future drug research and development processes that include testing for efficacy, tolerance and adverse effects in human trials. That process might also include chemical modifications to make the drug more efficient, better tolerated or both.

“Maybe we will need a cocktail of drugs, as is the case in many anti-AIDS treatments. But every drug that ends up surviving this long and winding road of development and testing starts as a hit that binds to a protein. It is this initial event that we are modeling here using supercomputers,” Dr. Baudry says.

“Normally it would take a very long time and a lot of money to achieve that, but with the supercomputers we can perform this initial hit discovery step much faster and cheaper,” he says. “Everything is being accelerated for COVID-19, so the whole process that can take up to a decade may end up being shorter here.”

More batches are being prepared for supercomputer testing, according to Baudry Lab researcher Dr. Kendall Byler, who is running the calculations on Sentinel. Dr. Byler is highly experienced in using computational approaches for natural product research.

“Actually, there are over 400,000 compounds we’d like to test,” Dr. Byler says.

Blocking proteins

In the initial batch, naturally occurring compounds were found that seem likely to bind to two important proteins, COVID-19’s papain-like protease, or PLpro, and the main protease, or Mpro. The proteins are enzymes from the virus’ genome that are responsible for processing all the virus’ proteins in infected cells. Infected cells are forced to manufacture them so that the virus can replicate.“If we can block these viral proteins from self-assembling and performing their functions inside the cell, we may not have been able to save that one infected cell, but we will prevent the virus from replicating and it will die with that cell,” Dr. Baudry says. “If we find a chemical that ‘sticks’ in these reactive regions of the proteins, the processing reactions will not be possible anymore and we will stop the infected cells from making and releasing more virus.”

The third protein of interest is COVID-19’s spike protein, which is how the virus attaches itself to a cell to initiate the infection process. This spike protein is present on the surface of the virus and gives the virus its characteristic crown-like (corona in Latin) appearance. It binds to a protein called ACE2 on the cell surface to begin the infection process.

“We are trying to find chemicals that would bind on the surface of the virus’ spike protein and prevent it from locking itself with the cell’s ACE2,” Dr. Baudry says.

In the initial batch modeled, scientists found the interactions of 24 compounds interesting in the spike protein, 41 molecules interesting in the main protein and 60 compounds interesting in the PL-pro protein.

“We can then have a good idea of what the natural products exhibit that makes them successful in these different proteins, and that is the starting point for screening larger databases of millions of chemicals much faster, helping chemists to synthesize novel molecules down the road, maybe more potent and more selective than the original natural products against these proteins,” Dr. Baudry says.

AI and ancient knowledge

Located in a Microsoft Azure data center in Texas, the Sentinel supercomputer makes the work more rapid than ever before possible and an HPE team is helping facilitate it. Dr. Baudry’s UAH team has access to Sentinel’s powerful capabilities through the cloud with Microsoft Azure.

Sentinel, which features HPE’s Cray XC50 end-to-end high-performance computing (HPC) system, is capable of computing 147 trillion floating point operations per second and can store 830,000 gigabytes of data.

Sentinel helps to cut compound testing time from months or even years to weeks, Dr. Baudry says. The supercomputer is as fast as the Earth’s entire population doing 20,000 calculations every second and has storage capacity for more than 45 years of high definition video.

The fight to prevent COVID-19’s sometimes devastating health consequences has created a new meeting of modern high-capacity artificial intelligence with humankind’s most ancient healing knowledge, Dr. Baudry says.

“Even five years ago, this would not have been possible,” he says. “It is fortunate for us that this kind of very advanced, very rapid computational power is available at this time when we need it so much.”

At UAH, the Baudry Lab collaborates on machine learning and big data in drug discovery with the laboratory of Dr. Vineetha Menon, an assistant professor of computer science.

The lab also collaborates in a separate COVID-19 compound search led by Oak Ridge National Laboratory (ORNL) in Tennessee and is working with the Alabama Supercomputer Center on COVID treatment compound research.

(Courtesy of UAH)

1 hour ago

Schoolyard Roots growing stronger, smarter kids in Alabama

When kids participate in the life of a garden, they see the complete cycle of growing food, cooking and preparing it to eat. School gardens are exciting places for kids to learn basic academic subjects, too.

The Tuscaloosa community came together more than 10 years ago to develop a garden-based learning program called the Druid City Garden project, now called Schoolyard Roots.

Schoolyard Roots employs a full-time teaching staff that provides garden lessons for students, as well as professional development training for teachers. The school gardens provide an outdoor experience rare to many students. They are more likely to make healthy choices and try new foods. Students gain a sense of responsibility, to collaborate and work together as a team.

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“When we see a child’s health and education improve, we know that we’re not only investing in that child’s life today – we’re helping them build a better future,” said Nicole Gelb Dugat, interim executive director. “Schoolyard Roots builds community through food. By increasing access to fresh, locally grown produce, we empower our community to make healthy and sustainable food choices.”

In March 2020, the impact of COVID-19 significantly affected the teaching community. Almost immediately, the Schoolyard Roots team began distributing produce from its gardens directly to local families. By the end of last year, the program had distributed more than 750 pounds of fresh garden vegetables to the community.

“We stewarded our gardens as fresh-air sanctuaries, where children and adults could relax, refocus and reconnect,” said Dugat. “Through it all, we shared vegetables and flowers. We cultivated moments of peace and learned together. We could not have done any of it without our incredible community of supporters.”

They found hope and inspiration in the small miracle of seeds planted by the students. Gardens bring joy, peace and courage in times of struggle. And gardens remind us to have hope for new growth and what is to come.

Schoolyard Roots partners with Tuscaloosa-area elementary schools to bring learning to life through teaching gardens. The nonprofit works in 11 elementary schools across Tuscaloosa County.

Its mission is to build healthy communities through food with the Gardens 2 Schools program.

Gardens support and encourage healthful eating as a key component of children’s physical wellbeing, which can aid their academic and social success, too. The garden is woven through many aspects of a school’s curriculum and adapted for different grade levels.

“The Gardens 2 Schools program cultivates curiosity,” Dugat said. “The program teaches the students how to work together (and) learn self-reliability and compassion.”

(Courtesy of Alabama NewsCenter)

2 hours ago

Has Washington’s stimulus measures saved our economy?

Congress is expected to soon pass President Biden’s $1.9 trillion COVID-19 stimulus package, the fourth major response to the pandemic. Did these measures save our economy from a protracted recession?

Our initial response might be yes because of last spring’s economic free-fall. The stock market declined 20%. Unemployment jumped from 3.5% in February to 14.8% in April, the highest level since the Great Depression. GDP fell 10% in the second quarter.

The economy stopped collapsing and began regaining ground. The stock market hit new record highs. Unemployment fell to 6.3% in January and inflation-adjusted GDP in the fourth quarter of 2020 was within 2% of the 2019 level. Post hoc ergo prompter hoc, however, is a logical fallacy.

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Macroeconomists disagree over whether government spending can lift an economy out of recession. Keynesians, following John Maynard Keynes’ analysis of the Great Depression, see a role for government stabilization. Austrians in the tradition of Ludwig von Mises and Friedrich Hayek argue that government often causes recessions. New classical analysis has blown many holes in Keynesian theories.

Regardless of the efficacy of a fiscal stimulus, our economy may not have faced a recession in 2020. The COVID-19 slump arguably resembled an off-season shutdown in a resort community more than a recession. Except that the pandemic shutdown was unexpected while seasonal closures are planned.

The economy could have been expected to bounce back on its own if the business closure and stay-at-home orders did not last too long. And this seemingly happened during the summer and fall.

How can we assess the stimulus spending? The Payroll Protection Plan and augmented unemployment likely kept some persons employed and softened the financial blow for idled workers. These programs could also be viewed as compensation owed by the government for business closure orders, not a stimulus. Personal saving has risen sharply, so many households’ stimulus checks produced little spending.

Unemployment programs have been beset by fraud. The Foundation for Government Accountability estimates that fraudulent schemes siphoned off $36 billion, more than the $26 billion in unemployment compensation paid out in all of 2019. Do Keynesians think fraud is a fiscal stimulus?

One trillion stimulus dollars were unspent as of January 2021. While some Republicans argued that we should spend this money before approving President Biden’s proposal, the unspent money was in the process of being spent. Still, money not yet spent did not stimulate the economy in 2020.

Proponents of fiscal stimulus warned that the economy would sputter without a fall stimulus. One forecast warned of a five percentage point increase in unemployment and 5% decline in GDP. The House and Senate did not agree on an encore to the CARES Act until December. And yet unemployment fell and GDP grew in the fourth quarter.

Even if some spending helped in 2020, the current stimulus package is almost certainly unnecessary. The Congressional Budget Office was already expecting growth to recover “rapidly,” with GDP surpassing the pre-pandemic level by mid-year and unemployment returning to its prior level by early 2022. For comparison, after the Great Recession unemployment did not reach its 2007 level until 2016.

President Biden’s package includes $500 billion to stabilize state budgets. States operate under balanced budget rules, so revenue declines due to the pandemic would trigger spending cuts potentially slowing the recovery. The $500 billion was based on an 8% decline in state revenues; the Wall Street Journal reports that revenues will be down only 1.6%.

Whatever the verdict on the stimulus spending, it worsened the national debt by about $3 trillion. The long-term debt impact may easily offset any short-term boost to the recovery.

The economic case that government spending can prevent or end a recession is weak. Fortunately, the COVID-19 shutdowns did not trigger a prolonged recession. While we might say, “Better safe than sorry,” the cost of the stimulus will be with us for years to come.

Daniel Sutter is the Charles G. Koch Professor of Economics with the Manuel H. Johnson Center for Political Economy at Troy University and host of Econversations on TrojanVision. The opinions expressed in this column are the author’s and do not necessarily reflect the views of Troy University.

2 hours ago

Packaging Corp. of America plans $440 million project at Alabama mill

JACKSON, Alabama – Packaging Corp. of America (PCA) plans to launch a three-year, $440 million project to permanently convert a paper machine at its mill in Clarke County to produce linerboard used for corrugated packaging.

Lake Forest, Illinois-based PCA announced that it discontinued the production of uncoated freesheet, used for copy paper and other applications, on its No. 3 paper machine at the Jackson mill in late 2020.

After a temporary switch to produce linerboard, PCA is now making preparations to convert the mill’s paper machine into a 700,000-ton-per-year high-performance, virgin kraft linerboard machine in a phased approach over the next 36 months.

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PCA said key elements in the conversion project include the installation of an OCC plant for recycling old corrugated containers and various pulp mill modifications. In addition, modifications and upgrades will be made to critical sections of the paper machine.

PCA Chairman and CEO Mark Kowlzan said the project will enable the company to meet strong packaging demand and to optimize the Alabama mill’s profitability and viability. The capital cost of the conversion is expected to be approximately $440 million.

“We are appreciative of the continued support from the State of Alabama, the Alabama Department of Commerce, the City of Jackson and Clarke County to help us continue providing quality jobs and a positive economic impact in the Jackson community,” Kowlzan said.

ECONOMIC IMPACT

Governor Kay Ivey said the project represents a positive development for the Jackson mill, a major industrial employer with more than 500 workers.

“Packaging Corp. of America’s reinvestment in its Jackson manufacturing facility will solidify the plant’s future by enhancing its competitiveness,” Governor Ivey said.

“This decision underlines the company’s confidence in its Alabama operation while also preserving jobs and safeguarding local education tax dollars. It’s a win for the company, the community and the state.”

Greg Canfield, Secretary of the Alabama Department of Commerce, said PCA’s project will increase the efficiency of the Clarke County plant while providing a long-term economic boost to Jackson, a city with a population of around 5,300.

“We’re committed to helping existing businesses grow and thrive in Alabama, and the impact of a major investment is always magnified when in happens in rural communities,” Secretary Canfield said.

“With this project, PCA is positioning its Jackson mill for the future, which will significantly benefit the city and the region for years to come.”

‘LONG-STANDING RELATIONSHIP’

Jackson Mayor Paul R. South said the project will allow PCA to continue providing quality jobs while securing a positive economic future for Clarke County.

“The City of Jackson looks forward to working with the corporation as the project moves forward,” South said. “In my opinion, they couldn’t have selected a better community.  Jackson is a safe and peaceful city full of great people, with good schools and recreation and a strong work force, along with extensive natural resources.”

“This is wonderful news for Clarke County and the City of Jackson,” said Stan Hutto, chairman of the Clarke County Commission. “We have a long-standing relationship with this outstanding company, and we are committed to helping them achieve their goals to ensure a bright, successful future.”

PCA is the third largest producer of containerboard products and the third largest producer of uncoated freesheet paper in North America. PCA operates eight mills and 90 corrugated products plants and related facilities.

The Jackson mill’s No. 1 paper machine will continue to produce uncoated freesheet products.

(Courtesy of Made in Alabama)

3 hours ago

Alabama’s Helen Keller was more than a hero for the disabled

She could neither see nor hear. But her vision influenced countless millions.

Helen Keller’s influence reached far beyond her native Alabama. She became a celebrity at an early age and remained so throughout her life.

Born in 1880 in Tuscumbia, Keller was 19 months old when an illness left her deaf and blind.

With the help of Anne Sullivan, her teacher for 49 years, she was able to learn how to communicate.

In her prime, she was traveling across the world making appearances and giving inspirational speeches.

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She became known for her tireless activism on behalf of workers’ and women’s rights, her literary work, and her tenure as an unofficial U.S. ambassador to the world.

“Helen Keller lived her life as an example of what people with disabilities could accomplish,” said Keller J. Thompson, her great grand-niece. “She so desired within her innermost being that people with disabilities be given a chance to prove the many things that they could do in this life. By her own experiences, she knew that people with disabilities could have great impacts on the world around them and every day of her life she was eager to be someone that impacted the world in a positive way, leaving it a better place than she found it.”

Keller attended several educational institutions and was accepted at Radcliffe College, where she graduated with honors, becoming the first deaf person to obtain a university degree.

According to an Encyclopedia of Alabama account, in the decades after college, Keller become increasingly involved in politics. She became an advocate of suffrage, unemployment benefits and legalized birth control for women.

She blamed industrialization and poverty for causing disability among a disproportionately large number of working-class people and became increasingly concerned about racial inequalities. She expressed her views through public speeches, newspaper and magazine articles, interviews and appearances at rallies.

Keller entered the 1920s seeking a meaningful public life and financial stability. The newly created American Foundation for the Blind (AFB) supplied both. Working on behalf of blind people with the AFB, Keller became a successful fundraiser and political lobbyist.

From the 1920s through the early 1940s, she worked to raise funds and lobby state and national legislatures. She emphasized educational and employment possibilities for people with disabilities, particularly those who were blind.

A trip to Japan in 1948 was the catalyst for Keller’s transformation from tourist to semi-official ambassador for the United States. Thrilled by her reception in Japan, the State Department worked with the AFB to fund and facilitate her travels and promote her as a representative of Americanism.

In 1964, President Lyndon Johnson awarded her the Congressional Medal of Freedom. When she died in 1968 at the age of 88, she was one of the most famous people in the world.

Keller’s journey from a deaf, blind girl to graduating from Radcliffe and becoming a prominent writer and political activist provided inspiration to millions of people with disabilities.

Although she left Alabama at the age of 8, she always claimed Ivy Green, her family’s house in Tuscumbia, as home, and she continued to identify herself as a Southerner throughout her life and travels.

Keller said: “Your success and happiness lie in you. Resolve to keep happy, and your joy and you shall form an invincible host against difficulties.”

Throughout March, Alabama NewsCenter is recognizing Alabama women of distinction, past and present, in celebration of Women’s History Month.

(Courtesy of Alabama NewsCenter)

3 hours ago

Rep. Aderholt warns congressional Democrats moving to allow for taxpayer-funded abortions

FLORENCE — Since 1976, the Hyde Amendment has banned the use of federal funds to pay for abortion except in the extreme case of saving the life of a pregnant woman or terminating a pregnancy that resulted from incest or rape.

The Hyde Amendment has stood the test time, most recently during the 2010 Affordable Care Act debate. However, U.S. Rep. Robert Aderholt (R-Haleyville) warns now that Democrats have the House, Senate and White House, the Hyde Amendment is in their crosshairs.

At an appearance before the Shoals Republican Club on Saturday, Aderholt discussed the possibility of Democrats ending the Hyde Amendment, adding it could come down to one or two Senate Democrats preventing a vote to end the filibuster rule in the U.S. Senate.

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“[O]ne of the things that is most egregious about what’s happening now is abortion — you know, one of those issues that has always been Democrats and Republicans have disagreed on. But one thing Democrats and Republicans could always somewhat agree on was federal funding of abortion off-limits. It’s one thing that if abortion would be allowed, and of course, I’m pro-life. I don’t agree with that. But at least the Democrats would embrace the idea we would not take federal government taxpayer dollars to fund abortion. That is out now. Democrats want to make it so federal funds, your tax dollars, can go for abortion. And that’s a really scary thing.”

“The Hyde Amendment is what we’re talking about. They want to destroy the Hyde Amendment. So, we’re going to do everything we can to make sure we keep the Hyde Amendment. It’s hard on Republicans — it’s hard on the House side, the Republicans being in the minority. Then on the Democrat side in the Senate with only 50 votes — then hopefully, we can get Manchin or some of those others to come along with us to try to make the rule out of order. We’re five seats basically from taking the majority in the House of Representatives.”

Aderholt was optimistic about Republicans’ chances in 2022 to regain control of the House but added his party had to be vigilant in the meantime.

@Jeff_Poor is a graduate of Auburn University and the University of South Alabama, the editor of Breitbart TV, a columnist for Mobile’s Lagniappe Weekly, and host of Mobile’s “The Jeff Poor Show” from 9 a.m.-12 p.m. on FM Talk 106.5.