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/

Moderna to Trial HIV and Flu Vaccines With mRNA Technology

The astonishing success of COVID-19 vaccines may signal a breakthrough in disease prevention technologyModerna is developing influenza and HIV vaccines using mRNA technology, the backbone of its effective COVID-19 vaccine. The biotech company is expected to launch phase 1 trials for its mRNA flu and HIV vaccines this year. If successful, mRNA may offer a silver lining to the decades-long fight against HIV, influenza, and other autoimmune diseases. Traditional vaccines often introduce a weakened or inactive virus to one’s body. In contrast, mRNA technology uses genetic blueprints, which build proteins to train the immune system to fight off the virus. Since mRNA teaches the body to recognize a virus, it can be effective against multiple strains or variants as opposed to just one.

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,”  said Rajesh Gandhi, MD, an infectious diseases physician at Massachusetts General Hospital and chair of HIV Medicine association.

Future mRNA vaccines have the potential to ward off multiple diseases with one shot, according to the Centers for Disease Control and Prevention (CDC).  Current mRNA vaccines, as demonstrated in their use against COVID-19, already appear to be less susceptible to new variants. “Based on its success in protecting against COVID-19, I am hopeful that mRNA technology will revolutionize our ability to develop vaccines against other pathogens, like HIV and influenza,” Gandhi says.

Moderna’s flu and HIV vaccines are still in early development stages, having yet to undergo their clinical trials. Still, if they prove successful, the mRNA-based treatment could dramatically change health care — both in expediting the route to immunity and by providing a solution to illnesses that have been around for decades. Scientists currently make annual alterations to the typical flu shot to keep up with the viruses in circulation. But a successful mRNA vaccine could provide a far more effective alternative.

An approved mRNA flu vaccine could be administered every other year rather than annually, explained virologist Andrew Pekosz, PhD. This is because mRNA accounts for variants and produces a stronger and longer-lasting immune response than that of the current flu vaccine, he says. The influenza vaccine is similar to the COVID-19 vaccine because the viruses have similar characteristics and necessary treatments, according to Pekosz.

However, a potential concern lies in the level of public immunity prior to receiving a vaccine. Since the flu has been around since the early 1900s, an mRNA vaccine could potentially boost older or less effective antibody responses rather than targeting current strains, Pekosz adds. “There’s no way to answer that question except to do some clinical trials, and see what the results tell us”.

Source: https://www.verywellhealth.com/

New Nanoparticle-delivered COVID-19 Vaccine

Researchers from Cleveland Clinic’s Global Center for Pathogen Research & Human Health have developed a promising new COVID-19 vaccine candidate that utilizes nanotechnology and has shown strong efficacy in preclinical disease models.

According to new findings published in mBio, the vaccine produced potent neutralizing antibodies among preclinical models and also prevented infection and disease symptoms in the face of exposure to SARS-CoV-2 (the virus that causes COVID-19). An additional reason for the vaccine candidate’s early appeal is that it may be thermostable, which would make it easier to transport and store than currently authorized COVID-19 vaccines.

Our vaccine candidate delivers antigens to trigger an immune response via nanoparticles engineered from ferritin–a protein found in almost all living organisms,” said Jae Jung, PhD, director of the Global Center for Human Health & Pathogen Research and co-senior author on the study. “This protein is an attractive biomaterial for vaccine and drug delivery for many reasons, including that it does not require strict temperature control.”

Added Dokyun (Leo) Kim, a graduate student in Dr. Jung’s lab and co-first author on the study, “This would dramatically ease shipping and storage constraints, which are challenges we’re currently experiencing in national distribution efforts. It would also be beneficial for distribution to developing countries.”

Other benefits of the protein nanoparticles include minimizing cellular damage and providing stronger immunity at lower doses than traditional protein subunit vaccines against other viruses, like influenza.

The team’s vaccine uses the ferritin nanoparticles to deliver tiny, weakened fragments from the region of the SARS-CoV-2 spike protein that selectively binds to the human entry point for the virus (this fragment is called the receptor-binding domain, or RBD). When the SARS-CoV-2 RBD binds with the human protein called ACE2 (angiotensin-converting enzyme 2), the virus can enter host cells and begin to replicate.

The researchers tested their vaccine candidate on a ferret model of COVID-19, which reflects the human immune response and disease development better than other preclinical models. Dr. Jung, a foremost authority in virology and virus-induced cancers, previously developed the world’s first COVID-19 ferret model–a discovery that has significantly advanced research into SARS-CoV-2 infection and transmission.

Source: https://www.lerner.ccf.org/
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https://www.eurekalert.org/

New Variant of SARS-CoV-2 Spreading Fast

A coronavirus variant called B1525 has become one of the most recent additions to the global variant watch list and has been included in the list of variants under investigation by Public Health England.

Scientists are keeping a watchful eye on this variant because it has several mutations in the gene that makes the spike protein – the part of the virus that latches onto human cells. These changes include the presence of the increasingly well-known mutation called E484K, which allows the virus to partly evade the immune system, and is found in the variants first identified in South Africa (B1351) and Brazil (P1).

While there is no information on what this means for B1525, there is growing evidence that E484K may impact how effective COVID vaccines are. But there is no suggestion so far that B1525 is more transmissible or that it leads to more severe disease.

There are other mutations in B1525 that are also noteworthy, such as Q677H. Scientists have repeatedly detected this changeat least six times in different lineages in the US, suggesting that it gives the virus an advantage, although the nature of any benefit has not been identified yet.

The B1525 variant also has several deletions – where “letters” (G, U, A and C) of the virus’s RNA are missing from its genome. These letters are also missing in B117, the variant first detected in Kent, England. Research by Ravindra Gupta, a clinical microbiologist at the University of Cambridge, found that these deletions may increase infectivity twofold in laboratory experiments.

As with many variants, B1525 appears to have emerged quite recently. The earliest example in the shared global database of coronavirus genomes, called Gisaid, dates from 15 December 2020. It was identified in a person in the UK. And like many variants, B1525 had already travelled the world before it came to global attention. A total of 204 sequences of this variant in Gisaid can be traced to 18 countries as of 20 February 2021.

Source: https://theconversation.com/

Amazon is now selling COVID-19 tests for customers to use at home

The DxTerity COVID-19 Saliva at-Home Collection Kit detects the presence of the virus but does not confirm immunity or detect antibodies. DxTerity‘s molecular-based PCR test received approval from the Food and Drug Administration last month. The test differs from the quicker and less expensive antigen tests, which use a nasal swab or throat swab to detect the virus.

A single COVID-19 testing kit is listed for $110, and a 10-pack bundle is available for $1,000.

Test takers must spit into a tube provided by the kit. The saliva sample is then inserted into a plastic bag and packed back into the box for shipment to one of DxTerity‘s laboratories certified by the Clinical Laboratory Improvement Amendments. Customers are also granted prepaid express return shipping with the test and should expect to receive results within 24 to 72 hours of sample receipt at the laboratory. DxTerity’s test is currently the only COVID-19 testing kit on Amazon.

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We have demonstrated the reliability and quality of our COVID-19 testing solution with big business and now we want to expand access to customers at home and small businesses,” said Bob Terbrueggen, founder and CEO of DxTerity, when he first announced the collaboration with the company last month. “Amazon is the perfect partner for expanding access to millions of U.S. customers.”

The test may not be valid for all travel purposes because sample collection is unsupervised, according to the product description. The Centers for Disease Control and Prevention recommends saliva specimens should be collected under supervision.

Amazon joins other retail giants in offering at-home COVID-19 saliva tests. Costco offers both regular and those approved for travel requirements to Hawaii, Bermuda and some other destinations for $129.99 and $139.99, respectively. However, the test has several dozen one-star reviews, with most complaining about delayed shipping and poor customer service from provider AZOVA.

Source: https://eu.usatoday.com/

COVID-19 Vaccine AstraZeneca confirms 100% protection against severe disease, hospitalisation and death

The primary analysis of the Phase III clinical trials from the UK, Brazil and South Africa, published as a preprint in The Lancet confirmed COVID-19 Vaccine AstraZeneca is safe and effective at preventing COVID-19, with no severe cases and no hospitalisations, more than 22 days after the first dose.

Results demonstrated vaccine efficacy of 76% (CI: 59% to 86%) after a first dose, with protection maintained to the second dose. With an inter-dose interval of 12 weeks or more, vaccine efficacy increased to 82% (CI: 63%, 92%).

The analysis also showed the potential for the vaccine to reduce asymptomatic transmission of the virus, based on weekly swabs obtained from volunteers in the UK trial. The data showed that PCR positive readings were reduced by 67% (CI: 49%, 78%) after a single dose, and 50% (CI: 38% to 59%) after the two dose regimen, supporting a substantial impact on transmission of the virus.

The primary analysis for efficacy was based on 17,177 participants accruing 332 symptomatic cases from the Phase III UK (COV002), Brazil (COV003) and South Africa (COV005) trials led by Oxford University and AstraZeneca, a further 201 cases than previously reported.

“This primary analysis reconfirms that our vaccine prevents severe disease and keeps people out of hospital. In addition, extending the dosing interval not only boosts the vaccine’s efficacy, but also enables more people to be vaccinated upfront. Together with the new findings on reduced transmission, we believe this vaccine will have a real impact on the pandemic,”said Sir Mene Pangalos, Executive Vice President BioPharmaceuticals R&D.

These new data provide an important verification of the interim data that has helped regulators such as the MHRA in the UK and elsewhere around the world to grant the vaccine emergency use authorisation. It also helps to support the policy recommendation made by the Joint Committee on Vaccination and Immunisation for a 12-week prime-boost interval, as they look for the optimal approach to roll out, and reassures us that people are protected 22 days after a single dose of the vaccine,” explained Professor Andrew Pollard, Chief Investigator of the Oxford Vaccine Trial, and co-author of the paper.

Data will continue to be analysed and shared with regulators around the world to support their ongoing rolling reviews for emergency supply or conditional approval during the health crisis. AstraZeneca is also seeking Emergency Use Listing from the World Health Organization for an accelerated pathway to vaccine availability in low-income countries.

The vaccine can be stored, transported and handled at normal refrigerated conditions (two-eight degrees Celsius/36-46 degrees Fahrenheit) for at least six months and administered within existing healthcare settings.

Source: https://www.astrazeneca.com/

COVID: the Risk of Death is 70% Higher for Male than for Female Patients

Evidence increasingly indicates that male sex is a risk factor for more severe disease and death from COVID-19. Male bias in COVID-19 mortality is observed in nearly all countries with available sex-disaggregated data, and the risk of death in males is ∼1.7 times higher than in females. Aging is strongly associated with higher risk of death in both sexes, but at all ages above 30 years, males have a significantly higher mortality risk, rendering older males the most vulnerable group. Sex differences are intertwined with differences in gender roles socially and with behavioral factors, which also influence COVID-19 incidence and outcomes. However, there are also possible biological mechanisms of male sex bias that affect the severity of COVID-19, particularly with respect to immune responses.

Sex differences beyond sex organs are present across species and extend to physiological systems, including the immune system. Infection by different pathogens results in differential immune responses and disease outcomes by sex, and although the pattern depends on age and other host factors, male sex is more often associated with lower immune responses and higher susceptibility and/or vulnerability to infections in animals. This is generally also the case in humans: Male patients have higher viral loads for hepatitis B virus (HBV) and HIV. Conversely, females generally mount a more robust immune response to vaccines, such as influenza vaccines. However, the heightened immune responses in females can also lead to detrimental immunopathology in infections.

The physiological response to virus infection is initiated when virus replication is detected by pattern recognition receptors. This leads to two antiviral programs by the infected cells.
Source: https://science.sciencemag.org/

First Antibody Treatment For COVID-19

Scientists in the UK have just recruited the first participants in the world to be part of a new long-acting antibody study. If the treatment is effective, it could give those who have already been exposed to SARS-CoV-2 protection from developing COVID-19.

We know that this antibody combination can neutralise the virus,explains University College London Hospitals (UCLH) virologist Catherine Houlihan. So we hope to find that giving this treatment via injection can lead to immediate protection against the development of COVID-19 in people who have been exposed – when it would be too late to offer a vaccine.”

This might not be the first antibody treatment for COVID-19 you’ve heard of. Outgoing US President Donald Trump was given monoclonal antibodies when he came down with the disease, and in the US two different antibody treatmentscasirivimab and imdevimab – received emergency approval back in November. But those antibody treatments are given to patients with mild or moderate COVID-19, who risk progressing to a severe version of the disease.

In a clinical trial of patients with COVID-19, casirivimab and imdevimab, administered together, were shown to reduce COVID-19-related hospitalisation or emergency room visits in patients at high risk for disease progression within 28 days after treatment when compared to placebo,the FDA explained in a press statement when the drugs were approved. This new antibody therapy, called AZD7442 and developed by UCLH and AstraZeneca, is a little different. AZD7442 is a combination of two monoclonal antibodies AZD8895 and AZD1061, which both target the receptor binding domain of the SARS-CoV-2 spike protein.

By targeting this region of the virus’s spike protein, antibodies can block the virus’s attachment to human cells, and, therefore, is expected to block infection,” the team wrote on the US ClinicalTrials.gov website.  “Amino acid substitutions have been introduced into the antibodies to both extend their half-lives, which should prolong their potential prophylactic benefit, and decrease Fc effector functionin order to decrease the potential risk of antibody-dependent enhancement of disease.”

Antibodies are little Y-shaped proteins that lock on to a particular section – called an antigen – of a virus, bacterium or other pathogen, and either ‘tag‘ it to be attacked by the immune system, or directly block the pathogen from invading our cells. Normal antibodies are produced by your body after an infection, while monoclonal antibodies are cloned in a lab and can be injected into a person already infected, to give the immune system a hand in the fight.

The researchers are hoping that AZD7442 – which is just starting the Storm Chaser study (the name for its phase 3 trial) – provides protection for those that have been exposed to the virus but do not yet have symptoms. Effectively, they’re trying to stop COVID-19 happening in the first place. “If you are dealing with outbreaks in settings such as care homes, or if you have got patients who are particularly at risk of getting severe COVID, such as the elderly, then this could well save a lot of lives,” said University of East Anglia infectious disease expert Paul Hunter.

Source: https://www.sciencealert.com/

Innovative Universal Flu Vaccine

For epidemiologists, the COVID-19 pandemic has greatly intensified their long-standing nightmare about another virus: the emergence of a new and deadly strain of flu. A universal flu vaccine, effective against any strain of the influenza virus that can infect humans, could protect us from this peril, but progress has been slow. A novel concept for one universal vaccine candidate has now passed its first test in a small clinical trial, its developers report today in Nature Medicine.

Seasonal flu vaccines induce antibodies against the “head” (slate) of the influenza surface protein hemagglutinin, but a new universal vaccine triggers antibodies (fragments of them shown in gray) that bind to the stalk (light blue) portion

This is an important paper,” says Aubree Gordon, an epidemiologist at the University of Michigan School of Public Health who studies influenza transmission and vaccines.

The influenza virus rapidly accumulates mutations and easily “reassorts,” or swaps, genes between strains, creating variants that can dodge any past immunity people had acquired naturally or from vaccines. That’s why a new flu vaccine must be developed each year. Existing flu vaccines contain weakened or inactivated influenza viruses with a mix of hemagglutinins (HAs), the proteins that stud their surfaces. These vaccines primarily aim to trigger antibody responses against HA’s top part, or head. Genetic changes in flu viruses rarely alter most of the head. But a small part of the head does reassort, or mutate, frequently, which allows new viral strains to dodge any immune memory and forces flu vaccinemakers to prepare new formulations each year, with updated HAs.
In the trial, 51 participants received the various vaccines and their antibodies were compared with those of 15 people who received placebos. A single shot of vaccine with chimeric HA inactivated viruses, the researchers report, “induced remarkably high antistalk antibody titers.”

Source: https://www.sciencemag.org/