Scientists at the University of California, Berkeley, have created a new COVID-19 therapeutic that could one day make treating SARS-CoV-2 infections as easy as using a nasal spray for allergies. The therapeutic uses short snippets of synthetic DNA to gum up the genetic machinery that allows SARS-CoV-2 to replicate within the body.

In a new study published online in the journal Nature Communications, the team shows that these short snippets, called antisense oligonucleotides (ASOs), are highly effective at preventing the virus from replicating in human cells. When administered in the nose, these ASOs are also effective at preventing and treating COVID-19 infection in mice and hamsters.

“Vaccines are making a huge difference, but vaccines are not universal, and there is still a tremendous need for other approaches,” said Anders Näär, a professor of metabolic biology in the Department of Nutritional Sciences and Toxicology (NST) at UC Berkeley and senior author of the paper. “A nasal spray that is cheaply available everywhere and that could prevent someone from getting infected or prevent serious disease could be immensely helpful.”

Because the ASO treatment targets a portion of the viral genome that is highly conserved among different variants, it is effective against all SARS-CoV-2 “variants of concern” in human cells and in animal models. It is also chemically stable and relatively inexpensive to produce at large scale, making it ideal for treating COVID-19 infections in areas of the world that do not have access to electricity or refrigeration.

If the treatment proves to be safe and effective in humans, the ASO technology could be readily modified to target other RNA viruses. The research team is already searching for a way to use this to disrupt influenza viruses, which also have pandemic potential.

“If we can design ASOs that target entire viral families, then when a new pandemic emerges, as long as we know which family the virus belongs to, we could use the nasally delivered ASOs to suppress the pandemic in its early stages,” said study first author Chi Zhu, a postdoctoral scholar in NST at UC Berkeley. “That’s the beauty of this new therapeutic.”

Source: https://news.berkeley.edu/

The relentless evolution of the COVID-causing coronavirus has taken a bit of the shine off the vaccines developed during the first year of the pandemic. Versions of the virus that now dominate circulation—Omicron and its subvariants—are more transmissible and adept at evading the body’s immune defenses than its original form. The current shots to the arm can still prevent serious illness, but their ability to ward off infection completely has been diminished. And part of the reason may be the location of the jabs, which some scientists now want to change.

To block infections entirely, scientists want to deliver inoculations to the site where the virus first makes contact: the nose. People could simply spray the vaccines up their nostrils at home, making the preparation much easier to administer. There are eight of these nasal vaccines in clinical development now and three in phase 3 clinical trials, where they are being tested in large groups of people. But making these vaccines has proven to be slow going because of the challenges of creating formulations for this unfamiliar route that are both safe and effective.

What could be most important about nasal vaccines is their ability to awaken a powerful bodily defender known as mucosal immunity, something largely untapped by the standard shots. The mucosal system relies on specialized cells and antibodies within the mucus-rich lining of the nose and other parts of our airways, as well as the gut. These elements move fast and arrive first, stopping the virus, SARS-CoV-2, before it can create a deep infection. “We are dealing with a different threat than we were in 2020,” says Akiko Iwasaki, an immunologist at Yale University. “If we want to contain the spread of the virus, the only way to do that is through mucosal immunity.”

Iwasaki is leading one of several research groups in the U.S. and elsewhere that are working on nasal vaccines. Some of the sprays encapsulate the coronavirus’ spike proteins—the prominent molecule that the virus uses to bind to human cells—into tiny droplets that can be puffed into the sinuses. Others add the gene for the spike to harmless versions of common viruses, such as adenoviruses, and use the defanged virus to deliver the gene into nasal tissue. Still others rely on synthetically bioengineered SARS-CoV-2 converted into a weakened form known as a live attenuated vaccine.

Sourc: https://www.scientificamerican.com/

Researchers at UC Davis Health have engineered a novel antibody, FuG1, that can directly interfere with the cell-to-cell transmission ability of SARS-CoV-2, the virus that causes COVID-19. FuG1 targets the enzyme furin, which the virus uses for its efficient chain of infections in human cells. The approach could be added to existing SARS-CoV-2 antibody cocktails for greater function against emerging variants.

“We developed an approach that interferes with the transmission chain of SARS-CoV-2. The COVID-19 vaccines are a great lifesaver in reducing hospitalizations and severe illness. Yet, we are now learning that they may not be as effective in controlling the transmissibility of the virus,” said Jogender Tushir-Singh, senior author of the study.

Tushir-Singh is an associate professor in the Department of Medical Microbiology and Immunology and a member of the UC Davis Comprehensive Cancer Center therapeutics program. His research uses rational protein engineering to generate multi-targeting antibodies as cancer therapeutics. When the pandemic hit, he began thinking of similar strategies that might work to limit the spread of the coronavirus.

Furin, found throughout the human body, is involved in various functions of cells. It is a type of enzyme, a protease, that can break down proteins into smaller components. It does this by cutting, or cleaving, the polybasic peptide bonds within the proteins. In cleaving these bonds, furin often acts as a switch, changing an inactive protein into an active one. For example, furin cleaves the inactive proparathyroid hormone into parathyroid hormone, which regulates calcium levels in the blood. It can also cleave and activate viruses that enter human cells. Pathogens that utilize furin in their human host include HIV, influenza, dengue fever and SARS-CoV-2.

When SARS-CoV-2 infects a human cell, it is in its active state, having already “cleaved” its spike protein, a key protein that binds to ACE2 receptors to gain entry. But when the virus is being synthesized within the host cell—when it is replicating—the spike is in an inactive state. The virus needs to use the host cell’s furin to cut the spike protein into two parts, S1 and S2, which makes the spike active on the viral particles for efficient transmissibility upon release.

“The virus exploits the host’s furin to transmit from one cell to another and another. This added activation step is what makes the virus highly transmissible,” said Tanmoy Mondal, the first author for the study and a post-doctoral researcher at UC Davis Health. But inhibiting furin to limit the SARS-CoV-2 chain of infection cycle is not a straightforward mechanism. “Furin is found throughout the human body and is needed for the normal functioning of many biological processes. Stopping furin from doing its job causes high body toxicity. That is why the standard furin inhibitor drugs are not a clinically feasible option,” Tushir-Singh said.

Instead, he and his team engineered a conjugated antibody targeting the SARS-CoV-2 spike protein. The design is similar to therapeutic monoclonal (IgG) antibodies but includes an added feature—Fc-extended peptide—that specifically interferes with the host furin. The researchers named this approach FuG1.

A study evaluating the efficacy of the engineered antibody was published in Microbiology Spectrum.

Source: https://phys.org/

A new surface that kills bacteria more than 100 times faster and more effectively than standard copper could help combat the growing threat of antibiotic-resistant superbugs. The new copper product is the result of a collaborative research project with RMIT University and Australia’s national science agency, CSIRO, with findings just published in Biomaterials. Copper has long been used to fight different strains of bacteria, including the commonly found golden staph, because the ions released from the metal’s surface are toxic to bacterial cells. But this process is slow when standard copper is used, as RMIT University’s Distinguished Professor Ma Qian explained, and significant efforts are underway by researchers worldwide to speed it up.

The copper magnified 500,000 times under a scanning electron microscope shows the tiny nano-scale pores in the structure

“A standard copper surface will kill about 97% of golden staph within four hours,” Qian said. “Incredibly, when we placed golden staph bacteria on our specially-designed copper surface, it destroyed more than 99.99% of the cells in just two minutes.” “So not only is it more effective, it’s 120 times faster.” Importantly, said Qian, these results were achieved without the assistance of any drug. “Our copper structure has shown itself to be remarkably potent for such a common material,” he said.

The team believes there could be a huge range of applications for the new material once further developed, including antimicrobial doorhandles and other touch surfaces in schools, hospitals, homes and public transport, as well as filters in antimicrobial respirators or air ventilation systems, and in face masks. The team is now looking to investigate the enhanced copper’s effectiveness against SARS-COV-2, the virus that causes COVID-19, including assessing 3D-printed samples. Other studies suggest copper may be highly effective against the virus, leading the US Environmental Protection Agency to officially approve copper surfaces for antiviral uses earlier this year.

Source: https://www.rmit.edu.au/news/

Using specialized carbon nanotubes, MIT engineers have designed a novel sensor that can detect SARS-CoV-2 without any antibodies, giving a result within minutes. Their new sensor is based on technology that can quickly generate rapid and accurate diagnostics, not just for Covid-19 but for future pandemics, the researchers say.

Using specialized carbon nanotubes, MIT engineers have designed a novel sensor that can detect SARS-CoV-2 without any antibody, giving a result within minutes.

“A rapid test means that you can open up travel much earlier in a future pandemic. You can screen people getting off of an airplane and determine whether they should quarantine or not. You could similarly screen people entering their workplace and so forth,” says Michael Strano, the Carbon P. Dubbs Professor of Chemical Engineering at MIT and the senior author of the study. “We do not yet have technology that can develop and deploy such sensors fast enough to prevent economic loss.”

The diagnostic is based on carbon nanotube sensor technology that Strano’s lab has previously developed. Once the researchers began working on a Covid-19 sensor, it took them just 10 days to identify a modified carbon nanotube capable of selectively detecting the viral proteins they were looking for, and then test it and incorporate it into a working prototype. This approach also eliminates the need for antibodies or other reagents that are time-consuming to generate, purify, and make widely available.

Several years ago, Strano’s lab developed a novel approach to designing sensors for a variety of molecules. Their technique relies on carbon nanotubes — hollow, nanometer-thick cylinders made of carbon that naturally fluoresce when exposed to laser light. They have shown that by wrapping such tubes in different polymers, they can create sensors that respond to specific target molecules by chemically recognizing them.

Their approach, known as Corona Phase Molecular Recognition (CoPhMoRe), takes advantage of a phenomenon that occurs when certain types of polymers bind to a nanoparticle. Known as amphiphilic polymers, these molecules have hydrophobic regions that latch onto the tubes like anchors and hydrophilic regions that form a series of loops extending away from the tubes.

MIT postdoc Sooyeon Cho and graduate student Xiaojia Jin are the lead authors of the paper, which appears today in Analytical Chemistry. Other authors include MIT graduate students Sungyun Yang and Jianqiao Cui, and postdoc Xun Gong.

Source: https://news.mit.edu/

The recent suggestion that ministers may have to consider culling or vaccinating animals to prevent the coronavirus from picking up another dangerous mutation and jumping back to humans may sound like sudden panic, but it’s just part of a long debate among scientists.

Evidence that cats could be infected with SARS-CoV-2, the virus that causes COVID, emerged as early as April 2020 from Wuhan, China. Evidence that they could also transmit the infection to other cats under particular conditions appeared in the same month. Since then, infections have been confirmed in mink in Denmark and the Netherlands, in big cats in zoos, in dogs, ferrets and a range of other species. It’s also worth remembering that the source of SARS-CoV-2 is probably bats and that other species of wildlife may also be infectable.

Infection of some of these species with SARS-CoV-2 can cause actual disease, creating veterinary, welfare or conservation problems. However, transmission to or from companion animals that spend a lot of time in close contact with people also presents extra problems for trying to control a pandemic in humans. For example, if transmission between humans and cats happens easily, then controlling the pandemic in people might require measures to prevent it, and that might include vaccinating and quarantining cats.

There is good evidence for transmission from humans to cats but very little evidence for transmission from cats to humans. Nor is there much evidence for transmission between cats in normal situations (that is, not in a laboratory). At the moment, there’s no real reason to be concerned that infections in cats are a major problem. You’re at much greater risk from your family and friends with COVID than from their cats, although you should take normal hygiene precautions you use to reduce the risks of catching other diseases (such as toxoplasmosis) from cats.

Source: https://theconversation.com

A new University of Chicago study has found that the drug masitinib may be effective in treating COVID-19. The drug, which has undergone several clinical trials for human conditions but has not yet received approval to treat humans, inhibited the replication of SARS-CoV-2 in human cell cultures and in a mouse model, leading to much lower viral loads.

Researchers at UChicago’s Pritzker School of Molecular Engineering (PME), working with collaborators at Argonne National Laboratory and around the world, also found that the drug could be effective against many types of coronaviruses and picornaviruses. Because of the way it inhibits replication, it has also been shown to remain effective in the face of COVID-19 variants.

“Inhibitors of the main protease of SARS-CoV-2, like masitinib, could be a new potential way to treat COVID patients, especially in early stages of the disease,” said Prof. Savas Tay, who led the research. “COVID-19 will likely be with us for many years, and novel coronaviruses will continue to arise. Finding existing drugs that have antiviral properties can be an essential part of treating these diseases.”

The results were published  in Science.

Source: https://pme.uchicago.edu/

Researchers say it’s the first real look at exactly what types of “red flags” the human body uses to enlist the help of T cells—killers the immune system sends out to destroy infected cells. Until now, COVID vaccines have focused on activating a different type of immune cell, B cells, which are responsible for creating antibodies. Developing vaccines to activate the other arm of the immune system—the T cells—could dramatically increase immunity against coronavirus, and importantly, its variants.

As reported in the journal Cell, the researchers say current vaccines might lack some important bits of viral material capable of triggering a holistic immune response in the human body.

“Companies should reevaluate their vaccine designs,” says Mohsan Saeed, a virologist at Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL) and co-corresponding author of the paper.

Saeed, an assistant professor of biochemistry at the School of Medicine, performed experiments on human cells infected with coronavirus. He isolated and identified those missing pieces of SARS-CoV-2 proteins inside one of the NEIDL’s Biosafety Level 3 (BSL-3) labs.

“This was a big undertaking because many research techniques are difficult to adapt for high containment levels [such as BSL-3],” Saeed says. “The overall coronavirus research pipeline we’ve created at the NEIDL, and the support of our entire NEIDL team, has helped us along the way.”

Saeed got involved when computational geneticists Pardis Sabeti and Shira Weingarten-Gabbay contacted him. They hoped to identify fragments of SARS-CoV-2 that activate the immune system’s T cells.

“The emergence of viral variants, an active area of research in my lab, is a major concern for vaccine development,” says Sabeti, a leader in the Broad Institute’s Infectious Disease and Microbiome Program. She is also a Harvard University professor of systems biology.

“We swung into full action right away because my laboratory had [already] generated human cell lines that could be readily infected with SARS-CoV-2,” Saeed says. The group’s efforts were spearheaded by two members of the Saeed lab: Da-Yuan Chen, a postdoctoral associate, and Hasahn Conway, a lab technician.

Source:  https://www.futurity.org/

More than a year after Covid-19 touched off the worst pandemic in more than a century, scientists have yet to determine its origins. The closest related viruses to SARS-CoV-2 were found in bats over 1,000 miles from the central Chinese city of Wuhan, where the disease erupted in late 2019. Initially, cases were tied to a fresh food market and possibly the wildlife sold there. An investigation in early 2021 has highlighted the possibility that they acted as a vector, transferring the virus from bats to humans. More politically charged theories allege the virus accidentally escaped from a nearby research laboratory, or entered China from another country via imported frozen food. Amid all the posturing, governments and scientists agree that deciphering the creation story.

Three closely related viruses to SARS-CoV-2 that had been collected during the previous 15 years. The closest, about 96% identical, was isolated from a species of horseshoe bat, Rhinolophus affinis, in the southern Chinese province of Yunnan in 2013. Some researchers have linked that particular virus to a mineshaft in Mojiang county there, where six men contracted a pneumonia-like disease in 2012 that killed three of them. Although they may share a common ancestor, the two are not similar enough to indicate SARS-CoV-2 was derived from the Yunnan virus. Sampling of bats in Hubei province, which includes Wuhan, haven’t found any positive for the pandemic strain. Coronaviruses sharing genetic features with SARS-CoV-2 have been found in other bat species and pangolins, a scaly, ant-eating mammal, elsewhere in Asia, highlighting the broad distribution that may have contributed to its evolution.

https://www.bloomberg.com/

An increasing body of research is pointing toward the possibility that COVID-19 causes the development of autoantibodies linked to other autoimmune diseases — and may be tied to the long-hauler symptoms associated with coronavirus.

In the latest preprint study (which means it has not yet undergone peer review) researchers analyzed the levels of 18 different autoantibodies between four groups:

• 29 unexposed pre-pandemic individuals from the general population
• 20 individuals hospitalized with moderate-to-severe COVID-19
• 9 recovering COVID-19-infected individuals with asymptomatic to mild viral symptoms during the acute phase, with samples collected between 1.8 and 7.3 months after infection
• 6 unexposed pre-pandemic subjects with lupus (an autoimmune disease that involves different kinds of autoantibodies)
• Autoantibodies are antibodies that mistakenly target your own tissues or organs and are associated with diseases such as rheumatoid arthritis and lupus. Unsurprisingly, the researchers found that autoantibodies were detected in five out of the six lupus subjects, compared to just 11 of 29 non-lupus, pre-pandemic controls.

However, the researchers also found that autoantibodies were detected in seven out of nine patients recovering from SARS-CoV-2 and in 12 out of the 20 hospitalized individuals with moderate to severe COVID-19. In the first group, autoantibodies were detected in all patients with reported persistent symptoms and two of the four without any long-term symptoms.

The autoantibodies that set SARS-CoV-2  infected patients apart from the pre-pandemic subjects are widely associated with myopathies (neuromuscular disorders), vasculitis (inflammation of the blood vessels), and antiphospholipid syndromes (when your body creates antibodies that make your blood much more likely to clot), all of which are conditions that share some similarities with COVID-19. The researchers note that these results underscore the importance of further investigating autoimmunity during a COVID-19 infection, and the role of autoimmunity in lingering symptoms. That said, they do urge caution in interpreting the results, which still need to undergo peer review.

“It’s a signal; it is not definitive,” lead researcher Nahid Bhadelia, MD, told the New York Times. “We don’t know how prevalent it is, and whether or not it can be linked to long COVID.” (Long COVID is sometimes used to describe the syndrome that causes long-hauler symptoms in those who have recovered from COVID-19.)

Still, as many as one-third of COVID-19 survivors say they still experience symptoms — and determining the role autoimmunity may play after coronavirus infection is critical.

“This is a real phenomenon,” Dr. Bhadelia said. “We’re looking at a second pandemic of people with ongoing potential disability who may not be able to return to work, and that’s a huge impact on the health symptoms.”

Source: https://creakyjoints.org/
AND
https://www.medrxiv.org/