How to Train AI to Generate Medicines and Vaccines

Scientists have developed artificial intelligence software that can create proteins that may be useful as vaccines, cancer treatments, or even tools for pulling carbon pollution out of the air. This research was led by the University of Washington School of Medicine and Harvard University.

The proteins we find in nature are amazing molecules, but designed proteins can do so much more,” said senior author David Baker, a professor of biochemistry at UW Medicine. “In this work, we show that machine learning can be used to design proteins with a wide variety of functions.

For decades, scientists have used computers to try to engineer proteins. Some proteins, such as antibodies and synthetic binding proteins, have been adapted into medicines to combat COVID-19. Others, such as enzymes, aid in industrial manufacturing. But a single protein molecule often contains thousands of bonded atoms; even with specialized scientific software, they are difficult to study and engineer. Inspired by how machine learning algorithms can generate stories or even images from prompts, the team set out to build similar software for designing new proteins. “The idea is the same: neural networks can be trained to see patterns in data. Once trained, you can give it a prompt and see if it can generate an elegant solution. Often the results are compelling — or even beautiful,” said lead author Joseph Watson, a postdoctoral scholar at UW Medicine.

The team trained multiple neural networks using information from the Protein Data Bank, which is a public repository of hundreds of thousands of protein structures from across all kingdoms of life. The neural networks that resulted have surprised even the scientists who created them.

Deep machine learning program hallucinating new ideas for vaccine molecules

The team developed two approaches for designing proteins with new functions. The first, dubbed “hallucination” is akin to DALL-E or other generative A.I. tools that produce new output based on simple prompts. The second, dubbed “inpainting,” is analogous to the autocomplete feature found in modern search bars and email clients.

Most people can come up with new images of cats or write a paragraph from a prompt if asked, but with protein design, the human brain cannot do what computers now can,” said lead author Jue Wang, a postdoctoral scholar at UW Medicine. “Humans just cannot imagine what the solution might look like, but we have set up machines that do.

To explain how the neural networkshallucinate’ a new protein, the team compares it to how it might write a book: “You start with a random assortment of words — total gibberish. Then you impose a requirement such as that in the opening paragraph, it needs to be a dark and stormy night. Then the computer will change the words one at a time and ask itself ‘Does this make my story make more sense?’ If it does, it keeps the changes until a complete story is written,” explains Wang.

Both books and proteins can be understood as long sequences of letters. In the case of proteins, each letter corresponds to a chemical building block called an amino acid. Beginning with a random chain of amino acids, the software mutates the sequence over and over until a final sequence that encodes the desired function is generated. These final amino acid sequences encode proteins that can then be manufactured and studied in the laboratory.

The research is published in the journal Science.

Source: https://newsroom.uw.edu/

mRNA Breakthrough Offers a Potential Heart Attack Cure

King’s College London researchers are turning to the same technology behind the mRNA COVID-19 vaccines to develop the first damage-reversing heart attack cure. They used mRNA to deliver the genetic instructions for specific proteins to damaged pig hearts, sparking the growth of new cardiac muscle cells. “The new cells would replace the dead ones and instead of forming a scar, the patient has new muscle tissue,” lead researcher Mauro Giacca said. Researchers are turning to the same technology behind Pfizer and Moderna’s vaccines to develop the first damage-reversing heart attack cure.

Diseases of the heart are the leading cause of death around the world; the WHO estimates that 17.9 million people died from cardiovascular disease in 2019, representing almost a third of all deaths. Of those, 85% are ultimately killed by heart attacks and strokes. Heart attacks occur when blood flow to parts of the heart is blocked, often due to fat or cholesterol build up. The cardiac muscle cells — marvelous little powerhouses that keep you beating throughout your entire life — are starved of oxygen and can be damaged or killed. Left in its wake is not the smoothly pumping cardiac muscle, but instead scar tissue.

We are all born with a set number of muscle cells in our heart and they are exactly the same ones we will die with. The heart has no capacity to repair itself after a heart attack,” explained Giacca.

At least, until now. To develop their heart attack cure, the researchers turned to mRNA, which delivers the instructions for protein creation to cells. Whereas the Pfizer and Moderna vaccines instruct cells to make the spike protein of SARS-CoV-2, priming the immune system against the virus, the same technology can deliver a potential heart attack cure by carrying the code for proteins that stimulate the growth of new heart cellsPharmaTimes reported. In an experiment with pigs (a close match for the human heart), the mRNA treatment stimulated new heart cells to grow after a heart attackregenerating the damaged tissues and creating new, functional muscle rather than a scar.

According to BioSpace, harnessing mRNA in this way has been dubbed “genetic tracking,” named for the way the mRNA’s progress is tracked via the new proteins it is creating. The technique is being explored to create vaccines for pathogens like HIV, Ebola, and malaria, as well as cancers and autoimmune and genetic diseases. While thus far their heart attack cure has only been successfully tested in porcine pumpers, the team hopes to begin human clinical trials within the next couple years. “Regenerating a damaged human heart has been a dream until a few years ago,” Giacca said, “but can now become a reality.”

Source: https://www.freethink.com/

Severe Covid-19 Doubles Risk Of Death In The Year After Illness

Survivors of severe Covid-19 are more than twice as likely to die over the following year than those who experienced milder symptoms or remained uninfected, according to new research published in Frontiers in Medicine, suggesting serious infections may cause significant damage to long-term health and underscoring the protection offered by vaccines. The risk following severe infection was particularly noteworthy in patients under 65, who had a 233% increased chance of dying compared to the uninfected, the researchers found. The increased risk of death for under 65s with severe Covid-19 was greater than that for those over the age of 65, the researchers found.

The research, by academics at the University of Florida, was based on an analysis of the electronic health records of 13,638 patients who underwent a PCR test for coronavirus within the University of Florida health system and recovered from the disease. The vast majority of patients—80%did not die from complications typically associated with Covid-19 like blood clotting or respiratory failure and died long after the initial infection had passed, the researchers said, meaning their deaths may never have been linked to Covid-19 by families or doctors. The findings suggest severe infection damages overall health and leaves patients vulnerable to other health issues, the researchers wrote, highlighting the importance of preventing serious illness through vaccination.

Patients with severe Covid-19 who recoveredwere at significantly greater risk of being hospitalized in the subsequent six months” said Arch Mainous, a professor at the University of Florida and the study’s lead author. “We must be especially vigilant in decreasing severe episodes of Covid-19” now we know it comes with a “substantial risk of dying from what would likely be considered to be an unrecognized complication… Taking your chances and hoping for successful treatment in the hospital doesn’t convey the full picture of the impact of Covid-19.”

While not able to prevent all infections, Covid-19 vaccines drastically cut the odds of severe illness and hospitalization in breakthrough cases. The vast majority of deaths from Covid-19 have been among the unvaccinated and hospitals in parts of the country have been pushed to their limits with a deluge of unvaccinated Covid-19 patients. Nearly a year after vaccines became freely and widely available in wealthy countries, leaders still lament the “pandemic of the unvaccinated” amid poor uptake and a resurgence of cases. Placing the immediate risk of Covid-19, this research supports a growing body of evidence outlining the persistent and sometimes new symptoms some coronavirus patients experience for weeks or months after their initial infection. The list of potentially debilitating symptoms for long Covid is long—one study identifies over 200—and covers the entire body, ranging from memory loss and hallucinations to tremors, fatigue and digestive issues. Research suggests that one in five Covid-19 patients will go on to be diagnosed with a mental illness within three months of recovery and conditions affecting the brain and thinking arecommon. Vaccines also appear to slash the risks of developing long Covidstudies suggest, though the precise mechanism of this is not yet understood, aside from preventing infection in the first place.

Source: https://www.frontiersin.org/
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https://www.forbes.com/

How To Reverse Cell Aging

A team of scientists has found why elderly people are more susceptible to COVID-19 and are working to reverse the aging process of the body’s immune system.

Scientists from the Technion-Israel Institute of Technology say they have found a way to rejuvenate the aging process of the body’s immune system. Prof. Doron Melamed and doctoral student Reem Dowery sought to understand why the elderly population is more susceptible to severe cases of COVID-19 and why the vaccines seem to be less effective and wane faster among this population. The results of their work were published this month in the peer-reviewed, online medical journal Blood.
The secret begins with B cells, also known as B lymphocytes. These are the cells that produce antibodies against any pathogen that enters the body. They play a key role in protecting people from viruses and diseases.
B cells do not just disappear. They turn into “memoryB cells so that if the body is exposed to a previous pathogen, the individual will not get sick. That is because the immune response will be fast and robust, and it will eliminate the pathogen, often without the individual knowing he or she had been exposed to it.


Imagine you are growing into adulthood, and you become an adult and then an older person,” Melamed said. “You accumulate in your body many memory cells. You are exposed all the time to pathogens, and hence you make more and more memory cells. Because these are so long-lived, there is no room left for new B cells.
What happens when a new pathogen, such as the coronavirus, comes along? There are no young B cells that can recognize it. That is one of the reasons why older people are more susceptible to severe COVID-19 and many other diseases. As noted, this happens because of the body’s need for homeostasis, something that Melamed’s lab discovered a decade ago. But this year, they took the discovery another step and figured out a mechanism to override the system.
We found specific hormonal signals produced by the old B cells, the memory cells, that inhibit the bone marrow from producing new B cells,” Melamed said. “This is a huge discovery. It is like finding a needle in a haystack.”

It also means that, over time, specific drugs or treatments can be found to inhibit one of the hormones in the signaling pathway and get the bone marrow to produce new B cells.

Source: http://www.jpost.com/

Single Dose Nanoparticle Vaccine Efficient To Produce Covid Antibodies

Across the world, health care workers and high-risk groups are beginning to receive COVID-19 vaccines, offering hope for a return to normalcy amidst the pandemic. However, the vaccines authorized for emergency use in the U.S. require two doses to be effective, which can create problems with logistics and compliance. Now, researchers reporting in ACS Central Science have developed a nanoparticle vaccine that elicits a virus-neutralizing antibody response in mice after only a single dose.

The primary target for COVID-19 vaccines is the spike protein, which is necessary for SARS-CoV-2’s entry into cells. Both of the vaccines currently authorized in the U.S. are mRNA vaccines that cause human cells to temporarily produce the spike protein, triggering an immune response and antibody production.

Peter Kim and colleagues wanted to try a different approach: a vaccine consisting of multiple copies of the spike protein displayed on ferritin nanoparticles. Ferritin is an iron storage protein found in many organisms that self-assembles into a larger nanoparticle. Other proteins, such as viral antigens, can be fused to ferritin so that each nanoparticle displays several copies of the protein, which might cause a stronger immune response than a single copy.

The researchers spliced spike protein and ferritin DNA together and then expressed the hybrid protein in cultured mammalian cells. The ferritin self-assembled into nanoparticles, each bearing eight copies of the spike protein trimer. The team purified the spike/ferritin particles and injected them into mice. After a single immunization, mice produced neutralizing antibody titers that were at least two times higher than those in convalescent plasma from COVID-19 patients, and significantly higher than those in mice immunized with the spike protein alone. A second immunization 21 days later produced even higher antibody levels. Although these results must be confirmed in human clinical trials, they suggest that the spike/ferritin nanoparticles may be a viable strategy for single-dose vaccination against COVID-19, the researchers say.

Source: https://www.acs.org/

AstraZeneca’s COVID-19 Vaccine Produces An Immune Response in Older People

Immunogenicity responses similar between older and younger adults

One of the world’s leading COVID-19 experimental vaccines produces a immune response in both old and young adults, raising hopes of a path out of the gloom and economic destruction wrought by the novel coronavirus.  The vaccine, developed by the University of Oxford, also triggers lower adverse responses among the elderly, British drug maker AstraZeneca Plc AZN.L, which is helping manufacture the vaccine, said on Monday. A vaccine that works is seen as a game-changer in the battle against the novel coronavirus, which has killed more than 1.15 million people, shuttered swathes of the global economy and turned normal life upside down for billions of people.

It is encouraging to see immunogenicity responses were similar between older and younger adults and that reactogenicity was lower in older adults, where the COVID-19 disease severity is higher,” an AstraZeneca spokesman said.

https://uk.reuters.com

Who Owns Scientific Data?

The coronavirus pandemic has rekindled a long-standing debate on whether viruses are a nation’s property, and if countries are obliged to share biological samples and scientific data that are key to developing life-saving treatments and vaccines. More than 6.5 million people are reported to have been infected globally, according to a Reuters tally.

China, where the novel coronavirus emerged late last year, shared the viral genetic sequence data (GSD) with the World Health Organization (WHO) in early January. That enabled laboratories around the world to start developing test kits, medications and vaccines.
Since then, however, a war of words has erupted around who gets access to vaccines and treatments first, with outrage over reports the U.S. administration tried to gain access to a potential vaccine being developed by a German firm.

It is morally wrong to think that someone has a stronger claim to a vaccine because they happen to live in a rich country,” said Mark Eccleston-Turner, co-author of a recent paper on the issue of viral sovereignty.

The international legal system encourages countries to look at viruses as their “sovereign resources that can be bargained and bartered away in exchange for future health goods such as vaccines,” he told the Thomson Reuters Foundation.

We need to move away from this model to one where viruses, and the health goods which are developed are seen as public goods, which everyone in the world has equal claim and access to,” said Eccleston-Turner, a lecturer at Britain’s Keele University.

Source: https://news.trust.org/

mRNA Are Super Potent Molecules, Fast And Efficient Against Coronavirus

CureVac AG, a clinical stage biopharmaceutical company pioneering mRNA-based drugs for vaccines and therapeutics, confirmed today that internal efforts are focused on the development of a coronavirus vaccine with the goal to reach, help and to protect people and patients worldwide. Based on its inherent mode of action, CureVac sees mRNA as one of the most potent molecules to provide fast and efficient solutions in outbreak scenarios, such like the Coronavirus. With inhouse expertise of over two decades and the company’s deep scientific understanding CureVac is leveraging its potent vaccine platform to focus on developing a potent, efficacious and safe and fast to produce vaccine against Covid-19.

CureVac recently announced successful vaccination results in its Rabies program fully protecting humans with two doses of only 1 microgram (1 millionth of a gram). These results are encouraging when thinking of supplying populations and people worldwide in a pandemic scenario. The company also has long and strong manufacturing expertise for mRNA-based vaccines and therapeutics since 2006. At this time, CureVac is working on expanding its manufacturing capacities to be able to provide up to billions of doses for outbreak situations like Covid-19.

Nature has invented mechanisms to activate our immune system against infectious diseases. With our unique messenger RNA technology we mimic nature and give our body the information how to fight against the virus. The combination of mRNA science, disease understanding, formulation and production expertise make CureVac a unique player to fight against any infectious disease, no matter whether they are seasonal or pandemic,” commented Mariola Fotin-Mleczek, Chief Technology Officer of CureVac.

Source: https://www.curevac.com/