Nanobody Cocktail Prevents SARS-CoV-2 from Infecting Mice

Small immune proteins, known as Nanobodies, can interfere with the SAR-CoV-2 virus and prevent it from latching into host cells. This exciting potential has been demonstrated by several research groups in studies using in vitro assays almost exclusively. However, new studies show that Nanobodies may prevent COVID-19 in vivo. In addition, a new study reports on the effectiveness of nanobody cocktails.

The new study was led by Dr. Wyhontam, an associate professor of infectious diseases at the Walter and Eliza Hall Institute (WEHI) in Australia. Tham and her WEHI team, in collaboration with scientists at the Doherty Institute and Kirby Institute, have created a nanobody cocktail consisting of two non-competitive Nanobodies with the involvement of angiotensin converting enzyme 2 (ACE2) with a receptor binding domain (RBD) variant. I found that I could block. It exists in a group of humans. The cocktail strongly neutralized both wild-type SARS-CoV-2 and N501YD614G variants at low concentrations.

Details posted online on April 23 Minutes of the National Academy of Sciences (((PNAS), In an article titled “Nanobody Cocktail Strongly Neutralizes SARS-CoV-2 D614G N501Y Mutant and Protects Mice”.

“Epitope mapping, X-ray crystallography, and cryo-electron microscopy revealed two different antigenic sites, showing two neutralized Nanobodies of different epitope classes that simultaneously bound to spike trimmers,” the article said. The author writes. “Prophylactic administration as a single Nanobody-Fc or mixture reduced viral load by up to 10.^Four-Fold in mice infected with the N501Y D614GSARS-CoV-2 virus. “

In essence, by mapping Nanobodies, scientists were able to identify Nanobodies that recognized the SARS-CoV-2 virus, including new global mutations of concern. Nanobodies also recognize the original SARS-CoV virus (which causes SARS) and show that it may provide cross-protection against these two human coronaviruses. The authors show that these results indicate that Nanobodies can provide an alternative to conventional antibody therapy for COVID-19.

Antibody-based therapies take advantage of the ability of antibodies to bind tightly and specifically to other proteins, disease-related proteins. Small antibodies, known as Nanobodies, are naturally produced by alpaca in response to infection.

As part of the current study, WEHI researchers oversaw immunization of a group of alpaca in Victoria with a non-infectious portion of the synthesis of SARS-CoV-2 “peplomer” protein.

“Synthetic peplomer is not infectious and does not cause alpaca to develop disease,” said Tam. “But it allows alpaca to develop Nanobodies. Next, we extract the sequence that encodes the Nanobodies and use them to generate millions of Nanobodies in the laboratory into spike proteins. You can choose the one that binds best. “

Next, we combined the major Nanobodies that block the invasion of viruses into a “Nanobody Cocktail.”

“By combining two major Nanobodies with this Nanobody cocktail, we were able to block SARS-CoV-2 from invading cells and test its viral load-reducing effect in preclinical models.” Explained Than.

By mapping Nanobodies, the research team was able to identify Nanobodies that recognized the SARS-CoV-2 virus. Nanobodies are also effective against the original SARS virus (SARS-CoV), demonstrating that they may provide cross-protection against these two globally important human coronaviruses.

“There has been a lot of debate about preparing for a pandemic in the wake of COVID-19,” Tam pointed out. “Nanobodies that can bind to other human betacoronaviruses such as SARS-CoV-2, SARS-CoV, and MERS may prove effective against future coronaviruses.”