Posts Tagged ‘ACE2 receptor’

Llama inspired “AeroNabs” to strangle COVID-19 with an inhaler 

Reporter : Irina Robu, PhD

Llama and other camelids fight off pathogens like viruses with tiny antibodies called nanobodies. A USCF team used protein engineering to make a synthetic nanobody that prevents the spike protein on the surface of SARS-CoV-2 from binding to healthy cells and infecting them. The team indicates promising preclinical results for aerosol formulation and can be used as a self-administered form of protein against the virus.

According to the UCSF team, an aerosolized form of nanobody exhibit SARS-CoV-2 incapable of binding to the ACE2 receptor on healthy cells that line airways. The synthetic nanobody stays functional after it was freeze-dried, exposed to heat and aerosolized.

The researchers ongoing screening a library of synthetic nanobodies, ultimately landing on 21 that banned the spike-ACE2 interaction. The scientists decided that in order to be truly efficient, a nanobody based treatment with interact with all three of the receptor binding domains on the spike protein that attaches to ACE2.  Their solution was to engineer a molecular chain that connects three nanobodies together, which would ensure that when one of the nanobodies attached to RBD, the others would link to the two remaining RBD. This molecular chain resulted in a drug candidate proved to be 200,000 times more potent than a single antibody.

At the same time, ExeVir Bio is also developing an aerosolized COVID-19 treatment inspired by llamas and is currently trying to advance its candidate into clinical trials by the end of the year. Their main candidate, VHH-72Fc was considered to bind to an epitope that is found both in SARS-CoV-2 and SARS-CoV. Yet, the llama inspired treatments are still behind antibody efforts like that of Regeneron.

Even though, there are multiple vaccines in development, researchers at UCSF believe that AeroNabs can be used as a sort of personal protective equipment until vaccines become available. The same researchers are planning human trials and are in discussion with partners who can provide manufacturing and distribution backing.



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Blood Clots Tied to Coronavirus Problems

Reporter: Irina Robu, PhD

Frequent complications of COVID-19 include purple rashes, swollen legs, clogged catheters and sudden death. Anyone with a severe illness is at risk of developing clots, but hospitalized patients with COVID-19 appear to be more susceptible. Blood clots in the deep veins of the body can occur due to injury/damage, inactivity, surgery, chemotherapy for cancer. Injuries like bone fractures or muscle tears can cause damage to blood vessels, leading to clots. Yes, due to long periods of inactivity, gravity causes blood to stagnate in the lowest areas of your body.

Yet, blood clots can form a variety of reasons. One of the most known blood clots that form in veins is pulmonary embolism caused by deep vein thrombosis. In some cases, a pulmonary embolism can be difficult to diagnose when you have an underlying lung or heart condition. It is possible that anything that gets in the bloodstream and then lodges in the smaller pulmonary arteries can be a pulmonary embolism.

Research from Netherlands and France suggest that clots appear in 20% to 30% of critically ill COVID-19 patients. Researchers have a few credible hypotheses to explain the phenomenon and they are starting to launch studies aimed at gaining mechanistic visions. But with the death toll rising, they are also scrambling to test clot-curbing medications. Common anticoagulant blood thinners such as warfarin and enoxaparin don’t reliably avert clotting in people with COVID-19 and young people are dying of strokes caused by the blockages in the brain. It is indicated that patients in the hospital have extremely elevated levels of a protein fragment called D-dimer, which is generated when a clot breaks down. High levels of D-dimer appear to be a powerful predictor of mortality in hospitalized patients infected with coronavirus.

Jeffrey Laurence, a hematologist at Weill Cornell Medicine in New York City studied lung and skin samples from three people infected with COVID-19 and found that the capillaries were clogged with clots. Even with all the research, how clotting occurs is still a mystery. One probability is that SARS-CoV-2 is unswervingly attacking the endothelial cells that line the blood vessels, which harbor the same ACE2 receptor that the virus uses to enter lung cells. This is confirmed by researchers from University Hospital Zurich in Switzerland and Brigham and Women’s Hospital in Boston, Massachusetts, who observed SARS-Cov-2 in endothelial cells inside kidney tissue.

Clotting can also be affected by the virus effects, because in some people COVID-19 prompts immune cells to release a torrent of chemical signals that ramps up inflammation. As the virus appears to activate the complement system, it then sparks clotting which acts a defense mechanism. People with the COVID-19 disease who become hospitalized usually have a number of risk factors for clotting such as high blood pressure, diabetes and/or genetic predisposition to clotting.

While researchers initiate how clotting occurs in people with COVID-19, they’re hurrying to test new therapies meant at preventing and busting clots. Blood-thinning medications are usually the standard of care for patients in the intensive-care unit and patients with COVID-19 are no exception. Similar trials are planned for scientists at Beth Israel Deaconess Medical Center have started enrolment for a clinical trial to evaluate an even more powerful clot-busting medication, tissue plasminogen activator. TPK is a drug more potent that carries higher risks of serious bleeding than do blood thinners. Scientists anticipate that these trials and others will deliver the data required to help physicians to make difficult treatment decisions.



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