Friday, August 14, 2020

Scientists Say They Developed a 'Nanobody' That Protects Against COVID-19

A group of around 50 scientists have developed a synthetic molecule that they say can be aerosolized and used to protect against COVID-19. The molecule is based on a tiny antibody originally found in llamas, camels, and alpacas.

The effort is a collaboration between different labs at University of California San Francisco and other labs across the country, in addition to one lab in France. The scientists have dubbed their synthetic molecule AeroNabs, and have shared their findings in a paper recently posted to the Biorxiv preprint server and a website for Walter Lab. The work has not yet appeared in a journal, and a statement from a school spokesperson said the decision to publish online first was made due to the urgency of the COVID-19 pandemic. 

“This work was done by an amazing collection of trainees and students who essentially worked tirelessly over the past four months and it's really their dedication that made this possible,” said Aashish Manglik, an assistant professor of pharmaceutical chemistry and one of the researchers in the project.

In the paper, the authors explain how AeroNabs can be used to protect against COVID-19 by preventing SARS-CoV-2, the virus that causes COVID-19, from attaching itself to cells found within the human body. According to the paper, this could be used as a prophylactic or a therapeutic agent in the early stages of infection. 

As part of the coronavirus viral family, SARS-CoV-2 relies on the spiked proteins that cover its surface to interact with ACE2 receptors, a protein found on the surface of several different cells including those of the lungs. Once the coronavirus has interacted with an ACE2 receptor, it can enter the cell and force the cell to reproduce more viruses in the body.

“Disruption of this interaction confers potent neutralization of viral entry, providing an avenue for vaccine design and for therapeutic antibodies,” the researchers write in their paper.

The result of their efforts is a synthetic “nanobody,” called AeroNabs, that they say can bind to the spiked protein of a coronavirus, locking it in an inaccessible down-state, and thus preventing it from interacting with ACE2 receptors and infecting the cell. Nanobodies are tiny antibodies originally found in llamas and camels that are about a tenth of the size of a regular antibody found in human blood. As a result, they have become great tools for a whole host of problems in biotechnology. In their research the scientists tested 2 billion different synthetic nanobodies against SARS-CoV-2 before coming up with AeroNabs.

“We clearly need drugs and vaccines to combat the pandemic, and likely a number of each, so interesting and promising approaches to new drugs are what we need—hopefully some will lead to effective therapies,” Jeffrey Kahn, director of the Johns Hopkins Berman Institute of Bioethics, told Motherboard in an email.

Manglik said AeroNabs could be used on people who live in the home of someone who has tested positive, or be administered to high-risk individuals like health care workers, nursing home staff, or nursing home residents, in addition to someone in the early stages of infection.

“For someone who just learned that they're PCR positive, that they're positive for the infection, we basically tell them to go home and quarantine until they develop symptoms. So for those people, we think that this would be really a unique solution and especially if you're high risk,” Manglik said.

For early stage infections, researchers envision AeroNabs binding to newly manufactured viruses and preventing them from infecting nearby cells, helping to ensure a person doesn’t get sicker. “AeroNabbed” viruses exhaled by an infected person also wouldn’t be capable of infecting other people since they would still be bound by the synthetic nanobody even when exhaled.

Manglik said the AeroNabs can be made very cheaply using either bacteria or yeast, and that they can also be dried down into a powder for shipping. He also said it is stable enough to be put into a nebulizer that would allow the molecule to be aerosolized. This suggests it could be self-administered through something like a nasal spray. He said the research team is currently in discussions with commercial partners to increase manufacturing and clinical testing to bring the synthetic nanobody outside an academic setting.

As research continues and scientists work to develop a vaccine for COVID-19, the containment of the disease’s spread will continue to depend a lot on policy and behavior. Until AeroNabs has gone through clinical trials it is too soon to determine what kind of impact it will have, but it’s a novel and interesting approach to tackling the pandemic.



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