COVID-19 Nanobodies Found-Illinois News Today

Washington [US], June 22 (ANI): Ohio State University scientists are new in the long-term fight against the SARS-CoV-2 virus by designing Nanobodies that can neutralize viral variants in two different ways. I am studying strategy. I am pursuing.

A preview of the article accelerated by this study was published online in the journal Nature.

In a lab study, researchers identified two groups of molecules that were effective against viral variants. Using different mechanisms, each group of Nanobodies evaded mutations and disabled the ability of the virus to bind to receptors that allow it to invade host cells.

While vaccination has made it possible to resume pre-pandemic activity in parts of the world, SARS-CoV-2 is rapidly working to avoid the vaccine by mutating itself. In this study, Nanobodies neutralized three new variants: alpha, beta, and gamma.

Kaishu, an assistant professor of veterinary and biological sciences at Ohio State University and co-lead author of the study, said: Therefore, multiple mechanisms must be used to control the spread of the virus. Nanobodies are antibodies derived from the immunity of camelids. Camels, llamas, alpaca-these can be redesigned into small molecules that mimic the structure and function of human antibodies.

In this study, researchers immunized the llama to produce a single-chain antibody against SARS-CoV-2. They also immunized “Nanomike” transgenic mice with a camel gene designed by researcher Jianliang Xu in the laboratory of Rafael Casellas, a senior researcher at the National Institute of Arthritis, Musculoskeletal and Dermatology (NIAMS). Manufactures Nanobodies. For camelids.

The team strengthens the power of Nanobodies by first immunizing the animal with a receptor binding domain (RBD) that is part of the viral surface peplomer, and then immunizing the animal with a booster shot that includes the entire peplomer. did.

“By using this continuous immune strategy, we have generated Nanobodies that can capture virions by recognizing receptor-binding domains with very high affinity,” said Xu.

Scientists have tested the neutralizing abilities of various Nanobodies, mapped the surface of RBDs, performed functional and structural analyzes, and discovered the strength of affinity to narrow down candidate molecules from a large library to six. did. I measured it.

Coronavirus is highly infectious because it binds very strongly to the ACE2 receptor, accesses human lung and nasal cells, and makes a copy of itself to infect other cells. The receptor binding domain of peplomer is the basis for successful binding to ACE2.

“The RBD-ACE2 interface is on top of the receptor-binding domain, which is the primary target of protective human antibodies produced by vaccination or previous infection to block the invasion of the virus,” said Xu. .. Mr. says. “But it is also a region that is frequently mutated in mutants.” So far, the method by which mutants have emerged is for current vaccines, as antibody efficacy is highly influenced by interface mutants. It’s long term. Researchers say it suggests that addiction will eventually endanger.

“We have discovered that certain Nanobodies can recognize the conserved regions of the receptor binding domain, which is a hidden place that is too narrow for human antibodies to reach,” says Xu. Also, if you connect to this location, it will work as intended, even if the RBD is a short distance away from where it connects to ACE2. That is, it blocks SARS-CoV-2 from invading the host cell.

Other groups of Nanobodies attracted to the RBD-ACE2 interface were unable to neutralize certain variants in their original form. However, when researchers designed this group to be homotrimers (three copies linked in tandem), Nanobodies achieved strong neutralization of the virus. Similarly, their effectiveness was improved by modifying the structure of Nanobodies connected to the RBD storage area.

More studies are available in the future, but findings suggest that Nanobodies may be a promising tool for preventing COVID-19 mortality when vaccines are at risk. Suggests.

“Our future plan is to find better solutions to vaccines by further isolating antibodies specifically against new mutants and learning from those antibodies for the development of treatments. ” He said.

Prior to entering Ohio, NIH HIV vaccine researcher Xu collaborated with several laboratories on this study. NIAMS’s Jianliang Xu and Rafael Casellas, and the National Institute of Allergy and Infectious Diseases Peter Kwong have contributed equally to this study. In addition to many NIH institutions, co-authors include Rockefeller University, Columbia University’s Aaron Diamond AIDS Research Center, and Frederick National Cancer Institute. (ANI)