Nano-Robots Injected into your Bloodstream to Fight Disease

What if there was a magical robot that could cure any disease? Don’t answer that. It’s a stupid question. Everyone knows there’s no one machine that could do that. But maybe a swarm made up of tens of thousands of tiny autonomous micro-bots could? That’s the premise laid out by proponents of nanobot medical technology. In science fiction, the big idea usually involves creating tiny metal robots via some sort of magic-adjacent miniaturization technology.

Luckily for us, the reality of nanobot tech is infinitely cooler. A team of researchers from Australia have developed a mind-blowing prototype that could work as a proof-of-concept for the future of medicine. Called “autonomous molecular machines,” the new nanotechnology eschews the traditional visage of microscopic metal automatons in favor of a more natural approach.

Inspired by biology, we design and synthesize a DNA origami receptor that exploits multivalent interactions to form stable complexes that are also capable of rapid subunit exchange”, explained the researchers. “DNA nanobots are synthetic nanometer-sized machines made of DNA and proteins. They’re autonomous because DNA itself is a self-assembling machine. Our natural DNA not only carries the code our biology is written in, it also knows when to execute. That’s part of the reason why, for example, your left and right feet tend to grow at roughly the same rate.”

Previous work in the field of DNA nanotechnology has demonstrated self-assembling machines capable of transferring DNA code, much like their natural counterparts. But the new tech out of Australia is unlike anything we’ve ever seen before.
Using the DNA origami receptor to demonstrate stable interactions with rapid exchange of both DNA and protein subunits, thus highlighting the applicability of the approach to arbitrary molecular cargo, an important distinction with canonical toehold exchange between single-stranded DNA. These particular nanobots can transfer more than just DNA information. Theoretically speaking, they could deliver any conceivable combination of proteins throughout a given biological system. To put that in simpler terms: the scientists should be able to eventually program swarms of these nanobots to hunt down bacteria, viruses, and cancer cells inside of our bodies. Each member of the swarm could carry a specific protein and, when they’ve found a bad cell, they could assemble their proteins into a formation designed to eliminate the threat.

Source: https://thenextweb.com/

Engineered Antibody Helps Block SARS-CoV-2 Transmission

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-19FuG1 targets the enzyme furin, which the  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  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 . Pathogens that utilize furin in their  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 , 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  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  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 featureFc-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/

 

New copper surface eliminates bacteria in just two minutes

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/

Two Studies Assess Pfizer’s Effectiveness Against Omicron

The Omicron variant substantially reduced antibody levels generated by the Pfizer-BioNTech COVID-19 vaccine, according to preliminary results from a South African study that’s still awaiting peer review. These are the first laboratory results to see how a COVID-19 vaccine holds up to Omicron. A team of researchers led by Africa Health Research Institute‘s Alex Sigal tested 14 blood samples from 12 people against a live sample of the Omicron variant. All 12 people were vaccinated, and six were previously infected.

Overall, the scientists found a roughly 40-fold reduction in the levels of neutralizing antibodies, the virus-fighting proteins that play a key role in our immune response, compared with the original version of the virus. Omicron did not evade vaccine protection completely, Sigal wrote on Twitter, meaning there’s still benefit to being vaccinated against this new variant. But the marked reduction in antibodies raises questions of how durable vaccine protection will be against Omicron – namely, whether booster shots will sufficiently ward off disease or if new vaccines may eventually be required. Sigal called it a “very large drop in neutralization of Omicron.”

A good booster probably would decrease your chance of infection, especially severe infection leading to more severe disease,” Sigal said in an online presentation of his results on Tuesday, according to Bloomberg. “People who haven’t had a booster should get one, and people who have been previously infected should be vaccinated.”

Shortly after Sigal announced his team’s results, another group of researchers at Sweden‘s Karolinska Institutet disclosed their own findings that suggested a substantial but less dramatic decline in antibody levels. The Karolinska team found a seven-fold reduction across 17 blood samples. They noted the impact of Omicron varied greatly between samples, and they used a version of Omicron that was artificially made in a lab instead of the live virus. A lead researcher for that group said the findings make Omicron “certainly worse than Delta, but, again, not as extreme as we expected.” The results are not finalized and have not been published in a medical journal. Sigal cautioned on Twitter that the findings “are likely to be adjusted as we do more experiments.”

Source: https://www.sciencealert.com/

World’s First COVID-19 DNA Vaccine

 India‘s drug regulator has granted emergency use approval for Zydus Cadila‘s COVID-19 vaccine, the world’s first DNA shot against the coronavirus, in adults and children aged 12 years and above. The approval gives a boost to India’s vaccination programme, which aims to inoculate all eligible adults by December, and will provide the first shot for those under 18, as the country still struggles to contain the virus spread in some states. The vaccine, ZyCoV-D, uses a section of genetic material from the virus that gives instructions as either DNA or RNA to make the specific protein that the immune system recognises and responds to. Unlike most COVID-19 vaccines, which need two doses or even a single dose, ZyCoV-D is administered in three doses.

The generic drugmaker, listed as Cadila Healthcare Ltd, aims to make 100 million to 120 million doses of ZyCoV-D annually and has already begun stockpiling the vaccineZydus Cadila‘s vaccine, developed in partnership with the Department of Biotechnology, is the second home-grown shot to get emergency authorization in India after Bharat Biotech‘s Covaxin. The drugmaker said in July its COVID-19 vaccine was effective against the new coronavirus mutants, especially the Delta variant, and that the shot is administered using a needle-free applicator as opposed to traditional syringes. The regulatory nod makes ZyCoV-D the sixth vaccine authorized for use in the country where only about 9.18% of the entire population has been fully vaccinated so far, according to Johns Hopkins data.

The firm had applied for the authorization of ZyCoV-D on July 1, based on an efficacy rate of 66.6% in a late-stage trial of over 28,000 volunteers nationwide.

https://www.reuters.com/

New Disinfectant Protects Against Covid for Up 7 Days

An alum and several researchers at the University of Central Florida (UCF) have used nanotechnology to develop the cleaning agent, which protects against seven viruses for up to seven days.

UCF researchers have developed a nanoparticle-based disinfectant that can continuously kill viruses on a surface for up to seven days – a discovery that could be a powerful weapon against COVID-19 and other emerging pathogenic viruses. The findings, by a multidisciplinary team of the university’s virus and engineering experts and the leader of an Orlando technology firm, were published this week in  ACS Nano, a journal of the American Chemical Society.

Christina Drake ’07PhD, founder of Kismet Technologies, was inspired to develop the disinfectant after making a trip to the grocery store in the early days of the pandemic. There she saw a worker spraying disinfectant on a refrigerator handle, then wiping off the spray immediately.

Initially my thought was to develop a fast-acting disinfectant,” she says, “but we spoke to consumers, such as doctors and dentists, to find out what they really wanted from a disinfectant. What mattered the most to them was something long-lasting that would continue to disinfect high-touch areas like doorhandles and floors long after application.”

Drake partnered with Sudipta Seal, a UCF materials engineer and nanoscience expert, and Griff Parks, a College of Medicine virologist who is also associate dean of research and director of the Burnett School of Biomedical Sciences. With funding from the U.S. National Science Foundation, Kismet Tech and the Florida High Tech Corridor, the researchers created a nanoparticle-engineered disinfectant.

Its active ingredient is an engineered nanostructure called cerium oxide, which is known for its regenerative antioxidant properties. The cerium oxide nanoparticles are modified with small amounts of silver to make them more potent against pathogens.

It works both chemically and mechanically,” says Seal, who has been studying nanotechnology for more than 20 years. “The nanoparticles emit electrons that oxidize the virus, rendering it inactive. Mechanically, they also attach themselves to the virus and rupture the surface, almost like popping a balloon.”

Most disinfecting wipes or sprays will disinfect a surface within three to six minutes of application but have no residual effects. This means surfaces need to be wiped down repeatedly to stay clean from a number of viruses, like COVID-19. The nanoparticle formulation maintains its ability to inactivate microbes and continues to disinfect a surface for up to seven days after a single application.

The disinfectant has shown tremendous antiviral activity against seven different viruses,” says Parks, whose lab was responsible for testing the formulation against “a dictionary” of viruses. “Not only did it show antiviral properties toward coronavirus and rhinovirus, but it also proved effective against a wide range of other viruses with different structures and complexities. We are hopeful that with this amazing range of killing capacity, this disinfectant will also be a highly effective tool against other new emerging viruses.

The scientists are confident the solution will have a major impact in health care settings in particular, reducing the rate of hospital acquired infections, such as Methicillin-resistant Staphylococcus Aureus (MRSA), Pseudomonas aeruginosa and Clostridium difficile – which affect more than one in 30 patients admitted to U.S. hospitals. And unlike many commercial disinfectants, the formulation has no harmful chemicals, which indicates it will be safe to use on any surface. Regulatory testing for irritancy on skin and eye cells, as required by the U.S. Environmental Protection Agency, showed no harmful effects.

Many household disinfectants currently available contain chemicals that can be harmful to the body with repeated exposure,” Drake says. “Our nanoparticle-based product will have a high safety rating will play a major role in reducing overall chemical exposure for humans.”

Source: https://www.ucf.edu/

Moderna Starts Human Trials for its Revolutionary HIV Vaccine Today

Today, the biotech company Moderna will start human trials for its HIV vaccine. Its HIV vaccine will be the first of its kind to use messenger RNA (mRNA), an approach that Moderna used in its effective COVID-19 vaccine.

The clinical trials will end sometime around spring 2023, according to the National Institutes of Health’s trial registry. They will involve 56 HIV-negative participants aged 18 to 56. The participants will be given one or two forms of mRNA that cause the body to form defenses against HIV infection.

In the past, HIV vaccines used inactivated forms of the virus. However, previous trials showed that these forms didn’t produce any immune responses. In fact, researchers canceled one trial in Thailand during the 2000s after inactivated forms of the virus were found to actually increase people’s risk of catching HIV rather than preventing infections.

Instead, the Moderna trials will contain one of two different types of mRNA: mRNA-1644 and mRNA-1644v2. These get the body’s cells to develop a “protein spike” on their surfaces. These spikes are similar to those embedded by HIV on a cell’s surface when it begins to infect cells to reproduce. When the body recognizes the presence of the mRNA spike, it begins producing antibodies to protect against infection. The mRNA may also allow scientists to make tweaks to the vaccine more easily.

The mRNA platform makes it easy to develop vaccines against variants because it just requires an update to the coding sequences in the mRNA that code for the variant,” Rajesh Gandhi, MD, an infectious diseases physician at Massachusetts General Hospital and chair of the HIV Medicine Association, told the medical site Verywell. This is especially helpful for HIV since the virus is known for having mutated into at least 16 known variants.

Source: https://www.lgbtqnation.com/

Highly Dangerous COVID Mutation Could Emerge in Cats

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

3 Existing Drugs Fight Coronavirus with ‘almost 100%’ Success

Israeli scientists say they have identified three existing drugs that have good prospects as COVID-19 treatments, reporting that they illustrated high ability to fight the virus in lab tests.

They placed the substances with live SARS‑CoV‑2 and human cells in vitro. The results “showed that the drugs can protect cells from onslaught by the virus with close to 100 percent effectiveness, meaning that almost 100% of the cells lived despite being infected by the virus,” Prof. Isaiah Arkin, the Hebrew University biochemist behind the research, told The Times of Israel.

By contrast, in normal circumstances, around half the cells would have died after two days following contact with the virus.” He added there are strong indications that the drugs will be robust against changing variants.

Arkin, part of a Hebrew University center that specializes in repurposing existing drugs, said that he screened more than 3,000 medicines for suitability, in what he describes as a needle-in-a-haystack search. This approach can provide a fast track to find treatments as the drugs have already been tried and tested, and he hopes to work with a pharmaceutical company to quickly get the medicines he identified clinically tested for COVID-19.

We have the vaccine, but we shouldn’t rest on our laurels, and I would like to see these drugs become part of the arsenal that we use to fight the coronavirus,” he said. When confronting SARS‑CoV‑2, the drugs in question — darapladib, which currently treats atherosclerosis; the cancer drug Flumatinib; and an HIV medicine — don’t target the spike protein. Rather, they target one of two other proteins: the envelope protein and the 3a protein. These proteins — especially the envelope proteinhardly change between variants, and even between diseases from the coronavirus family. As such, drugs that target them are likely to remain effective in spite of mutations, Arkin said.

Source: https://www.timesofisrael.com/

The Virus Trap

To date, there are no effective antidotes against most virus infections. An interdisciplinary research team at the Technical University of Munich (TUM) has now developed a new approach: they engulf and neutralize viruses with nano-capsules tailored from genetic material using the DNA origami method. The strategy has already been tested against hepatitis and adeno-associated viruses in cell cultures. It may also prove successful against corona viruses.

There are antibiotics against dangerous bacteria, but few antidotes to treat acute viral infections. Some infections can be prevented by vaccination but developing new vaccines is a long and laborious process.

Now an interdisciplinary research team from the Technical University of Munich, the Helmholtz Zentrum München and the Brandeis University (USA) is proposing a novel strategy for the treatment of acute viral infections: The team has developed nanostructures made of DNA, the substance that makes up our genetic material, that can trap viruses and render them harmless.

Lined on the inside with virus-binding molecules, nano shells made of DNA material bind viruses tightly and thus render them harmless.

Even before the new variant of the corona virus put the world on hold, Hendrik Dietz, Professor of Biomolecular Nanotechnology at the Physics Department of the Technical University of Munich, and his team were working on the construction of virus-sized objects that assemble themselves.

In 1962, the biologist Donald Caspar and the biophysicist Aaron Klug discovered the geometrical principles according to which the protein envelopes of viruses are built. Based on these geometric specifications, the team around Hendrik Dietz at the Technical University of Munich, supported by Seth Fraden and Michael Hagan from Brandeis University in the USA, developed a concept that made it possible to produce artificial hollow bodies the size of a virus.

In the summer of 2019, the team asked whether such hollow bodies could also be used as a kind of “virus trap”. If they were to be lined with virus-binding molecules on the inside, they should be able to bind viruses tightly and thus be able to take them out of circulation. For this, however, the hollow bodies would also have to have sufficiently large openings through which viruses can get into the shells.

None of the objects that we had built using DNA origami technology at that time would have been able to engulf a whole virus – they were simply too small,” says Hendrik Dietz in retrospect. “Building stable hollow bodies of this size was a huge challenge.”

Starting from the basic geometric shape of the icosahedron, an object made up of 20 triangular surfaces, the team decided to build the hollow bodies for the virus trap from three-dimensional, triangular plates. For the DNA plates to assemble into larger geometrical structures, the edges must be slightly beveled. The correct choice and positioning of binding points on the edges ensure that the panels self-assemble to the desired objects.

In this way, we can now program the shape and size of the desired objects using the exact shape of the triangular plates,” says Hendrik Dietz. “We can now produce objects with up to 180 subunits and achieve yields of up to 95 percent. The route there was, however, quite rocky, with many iterations.”

By varying the binding points on the edges of the triangles, the team’s scientists can not only create closed hollow spheres, but also spheres with openings or half-shells. These can then be used as virus traps.

Source: https://www.tum.de/