Spike protein crosses the blood-brain barrier

Summary:-  In a new study, researchers found that the spike protein, often depicted as the red arms of the virus, can cross the blood-brain barrier in mice. The spike proteins alone can cause brain fog. 

https://blog-yard-garden-news.extension.umn.edu/2020/03/covid-19-can-virus-be-transmitted-on.html

And researchers are discovering why. The SARS-CoV-2 virus, like many viruses before it, is bad news for the brain. during a study published Dec.16 in Nature Neuroscience, researchers found that the spike protein, often depicted because the red arms of the virus, can cross the barrier in mice.

This strongly suggests that SARS-CoV-2, the explanation for COVID-19, can enter the brain.

The spike protein, often called the S1 protein, dictates which cells the virus can enter. Usually, the virus does an equivalent thing as its binding protein, said corresponding author William A. Banks, a professor of drugs at the University of Washington School of drugs and a Puget Sound Veterans Affairs Healthcare System physician and researcher. Banks said binding proteins like S1 usually by themselves cause damage as they detach from the virus and cause inflammation.

“The S1 protein likely causes the brain to release cytokines and inflammatory products,” he said.

In science circles, the extreme inflammation caused by the COVID-19 infection is named a cytokine storm. The system , upon seeing the virus and its proteins, overreacts in its plan to kill the invading virus. The infected person is left with brain fog, fatigue and other cognitive issues.

Banks and his team saw this reaction with the HIV virus and wanted to ascertain if an equivalent was happening with SARS CoV-2.

Banks said the S1 protein in SARS-CoV2 and therefore the gp 120 protein in HIV-1 function similarly. they’re glycoproteins — proteins that have tons of sugars on them, hallmarks of proteins that bind to other receptors. Both these proteins function because the arms and hand for his or her viruses by grabbing onto other receptors. Both cross the barrier and S1, like gp120, is probably going toxic to brain tissues.

“It was like reminder ,” said Banks, who has done extensive work on HIV-1, gp120, and therefore the barrier .

The Banks’ lab studies the barrier in Alzheimer’s, obesity, diabetes, and HIV. But they put their work on hold and every one 15 people within the lab started their experiments on the S1 protein in April. They enlisted long-time collaborator Jacob Raber, a professor within the departments of Behavioral Neuroscience, Neurology, and Radiation Medicine, and his teams at Oregon Health & Science University.

The study could explain many of the complications from COVID-19.

“We know that once you have the COVID infection you’ve got trouble breathing and that is because there’s infection in your lung, but a further explanation is that the virus enters the respiratory centers of the brain and causes problems there also ,” said Banks.

Raber said within the ir experiments transport of S1 was faster in the neural structure and kidney of males than females. This observation might relate to the increased susceptibility of men to more severe COVID-19 outcomes.

As for people taking the virus lightly, Banks features a message:

“You don’t want to mess with this virus,” he said. “Many of the consequences that the COVID virus has might be accentuated or perpetuated or maybe caused by virus getting into the brain and people effects could last for a really while .”

This study was partially supported by a National Institute on Aging-funded COVID-19 supplement to a shared RF1 grant of Banks and Raber.

Mini antibodies against COVID-19 from a llama

Summary: Researchers have isolated a group of promising, tiny antibodies, or ‘nanobodies,’ against SARS-CoV-2 that were produced by a llama named Cormac. Preliminary results suggest that a minimum of one among these nanobodies, called NIH-CoVnb-112, could prevent infections and detect virus particles by grabbing hold of SARS-CoV-2 spike proteins. additionally , the nanobody seemed to work equally well in either liquid or aerosol form, suggesting it could remain effective after inhalation.

Photo by Jessica Knowlden on Unsplash

National Institutes of Health researchers have isolated a group of promising, tiny antibodies, or “nanobodies,” against SARS-CoV-2 that were produced by a llama named Cormac.

Preliminary results published in Scientific Reports suggest that a minimum of one among these nanobodies, called NIH-CoVnb-112, could prevent infections and detect virus particles by grabbing hold of SARS-CoV-2 spike proteins. additionally , the nanobody seemed to work equally well in either liquid or aerosol form, suggesting it could remain effective after inhalation. SARS-CoV-2 is that the virus that causes COVID-19.


The study was led by a pair of neuroscientists, Thomas J. “T.J.” Esparza, B.S., and David L. Brody, M.D., Ph.D., who add a brain imaging lab at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS).

“For years TJ and that i had been testing out the way to use nanobodies to enhance brain imaging. When the pandemic broke, we thought this was a once during a lifetime, all-hands-on-deck situation and joined the fight,” said Dr. Brody, who is additionally a professor at Uniformed Services University for the Health Sciences and therefore the senior author of the study. “We hope that these anti-COVID-19 nanobodies could also be highly effective and versatile in combating the coronavirus pandemic.”

A nanobody may be a special sort of antibody naturally produced by the immune systems of camelids, a gaggle of animals that has camels, llamas, and alpacas. on the average , these proteins are a few tenth the load of most human antibodies.

This is often because nanobodies isolated within the lab are essentially free-floating versions of the ideas of the arms of heavy chain proteins, which form the backbone of a typical Y-shaped human IgG antibody. The following pointers play a critical role within the immune system’s defenses by recognizing proteins on viruses, bacteria, and other invaders, also referred to as antigens.

Because nanobodies are more stable, less costly to supply , and easier to engineer than typical antibodies, a growing body of researchers, including Mr. Esparza and Dr. Brody, are using them for medical research. as an example , a couple of years ago scientists showed that humanized nanobodies could also be simpler at treating an autoimmune sort of thrombotic idiopathic thrombocytopenic purpura , a rare blood disease , than current therapies.

Since the pandemic broke, several researchers have produced llama nanobodies against the SARS-CoV-2 spike protein which will be effective at preventing infections. within the current study, the researchers used a rather different strategy than others to seek out nanobodies which will work especially well.

“The SARS-CoV-2 spike protein acts sort of a key. It does this by opening the door to infections when it binds to a protein called the angiotensin converting enzyme 2 (ACE2) receptor, found on the surface of some cells,” said Mr. Esparza, the lead author of the study. “We developed a way that might isolate nanobodies that block infections by covering the teeth of the spike protein that bind to and unlock the ACE2 receptor.”

To do this, the researchers immunized Cormac five times over 28 days with a purified version of the SARS-CoV-2 spike protein. After testing many nanobodies they found that Cormac produced 13 nanobodies which may be strong candidates. Initial experiments suggested that one candidate, called NIH-CoVnb-112, could work alright.

Test Tube studies showed that this nanobody sure to the ACE2 receptor 2 to 10 times stronger than nanobodies produced by other labs. Other experiments suggested that the NIH nanobody stuck on to the ACE2 receptor binding portion of the spike protein.
Then the team showed that the NIH-CoVnB-112 nanobody might be effective at preventing coronavirus infections.

To mimic the SARS-CoV-2 virus, the researchers genetically mutated a harmless “pseudo virus” in order that it could use the spike protein to infect cells that have human ACE2 receptors. The researchers saw that relatively low levels of the NIH-CoVnb-112 nanobodies prevented the pseudo virus from infecting these cells in petri dishes.

Importantly, the researchers showed that the nanobody was equally effective in preventing the infections in petri dishes when it had been sprayed through the type of nebulizer, or inhaler, often wont to help treat patients with asthma.


“One of the exciting things about nanobodies is that, unlike most regular antibodies, they will be aerosolized and inhaled to coat the lungs and airways,” said Dr. Brody.
The team has applied for a patent on the NIH-CoVnB-112 nanobody.