Engineered Nanobodies Offer Hope in the Long Run Against COVID-19 and its Variants

Since COVID-19 appears to be a long and protracted battle for mankind with its continuously emerging variants, researchers are looking into engineered nanobodies to give us a fighting chance.

Studies are looking into the use of these engineered nanobodies that can potentially disable the  SARS-CoV-2 coronavirus and its variants in two different ways. Previous laboratory studies revealed that two groups of molecules were particularly effective against virus variants. By utilizing different mechanisms, nanobodies in each of the two groups were able to bypass mutations, disabling the SARS-CoV-2 ability to bind to our receptor proteins, which in turn allow them to enter and infect the host cells.

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LONDON, ENGLAND - JUNE 14: Coronavirus safety posters are displayed in the window of the Sondheim Theatre on June 14, 2021, in London, England. Prime Minister Boris Johnson has confirmed a four-week delay to the final easing of coronavirus restrictions following concern over the virus's Delta variant and rising infection rates.

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An Extended Crusade Against COVID-19

While vaccination is helping mankind ease back into the life before the pandemic in some parts of the world, other areas are already facing new versions of the disease. Caused by mutations in the SARS-CoV-2 virus, some of these region-specific variants are posing problems by rendering existing vaccines ineffective. In the study presented in the latest Nature journal, titled "Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants," researchers conducted tests on three emerging COVID-19 variants: Alpha, Beta, and Gamma. The engineered nanobodies were able to neutralize these variants.

These engineered nanobodies are antibodies that are derived from the immunization of members of the camelid family - camels, alpacas, llamas, guanacos, and the like. The naturally occurring antibodies are then re-designed into fabricated molecules that can copy human antibodies in terms of structure and function.

In the new study, researchers had llamas undergo immunization to allow them to create single-chain antibodies against SARS-CoV-2. They also conducted the same process for "nanomice," or transgenic mice that had camelid genes inserted into them by research fellow Jianliang Xu, senior investigator from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). The genetic modification conducted on the nanomice allowed them to synthesize the same nanobodies as those from other camelids in the study.

The team then increased the potency of these nanobodies by first immunizing animals with the receptor-binding domain (RBD), which is a segment of the viral surface spike protein. They then followed it with booster shots containing the rest of the spike protein.

"By using this sequential immunization strategy, we generated nanobodies that can capture the virion by recognizing the receptor-binding domain with very high affinity," Xu said in a news release from the Ohio State University.

Engineered Nanobodies Fight Off SARS-CoV-2 Variants

Researchers then tested the capacity of these engineered nanobodies against SARS-CoV-2 and its variants by mapping the RBD surface, conducting structural and functional analyses, and measuring the strength of the nanobodies' respective affinities to narrow candidate molecules from a large library down to six.

What made COVID-19 highly contagious is that it binds tightly to the ACE2 receptor, gaining access to nasal cavity cells and lung cells in humans where it replicates and spreads. The infection begins with the response of the receptor-binding domain on the spike protein, which determines its ability to attach itself and later replicate.

While there are more processes needed to successfully utilize these engineered nanobodies, the new study shows their promising capabilities in ensuring our safety against the evolving SARS-CoV-2.

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