Hump day for blocking coronavirus

Engineered camelid nanobodies sheath coronavirus spikes

Original source: Materials Today

Nanobodies that might be formulated into an oral inhaler or a nasal spray could be administered by an individual to disable the protein spikes on the surface of viral particles. Such spikes are a key feature of the SARS-CoV-2 virus that causes Covid-19. The nanoparticles would act like a synthetic vaccine crippling the virus and preventing it from infecting human cells and so replicating. The research has not yet been peer-reviewed but is available for independent assessment by others on the bioRxiv preprint server [Schoof, M. et al; BioRxiv (2020) DOI: 10.1101/2020.08.08.238469]

Much effort is being put into the search for a vaccine for the coronavirus disease in which humanity finds itself engulfed in 2020. Unfortunately, as many experts have pointed out, we have no vaccines for other coronaviruses. It might be that humans can never develop a persistent immune response to this disease through naturally acquired immunity in those who have survived infection. More worryingly, it might be that we can never develop a vaccine that triggers a strong response and raises antibodies to disease in the way that familiar vaccines for polio, tuberculosis, measles, and other diseases do.

Michael Schoof of the University of California at San Francisco and colleagues describe their putative anti-Covid inhaler as a form of molecular PPE (personal protection equipment) that might be used as a preventer in the same way that people with asthma or allergic rhinitis might use their preventer inhalers to ward off symptoms of those conditions. Indeed, in the absence of persistent immunity or access to a vaccine, a manufactured product of this sort could become de rigeur in the new normal in which we find ourselves, acting as chemical PPE against infection.

Intriguingly, the team’s long-term research, which began before the current pandemic, took inspiration from immune proteins discovered in the late 1980s in camelids, the group of animals that includes the camel and the llama, where they are part of the animals’ natural defenses against disease. These proteins are much smaller than antibodies, nanoscopically small in fact, but still have many of their characteristics of antibodies and so were dubbed nanobodies. The UCSF team and their collaborators searched a previously created database of more than two billion engineered nanobodies to find ones that might block the infecting spikes on the SARS-CoV-2 viral particles and preclude it from interacting with its target receptor in the body.

Their search plucked out just 21 nanobodies from the database, which they then examined in the laboratory using cryo-electron microscopy. This technique revealed that the successful nanobodies could sheath the spikes on the SARS-CoV-2 virus, which might ultimately prove to be the downfall of the virus. Further tests on the three most promising of the 21 nanobodies against “live” virus showed them to be extremely potent at deactivating it even at very low doses. The strongest of the nanobodies not only sheaths the spikes but clamps shut on the inactive spike before it ever becomes activated on the viral particle surface, doubling up the PPE effect, as it were.

The next stage was to create mutant versions of the most potent of the nanobodies. The team swapped out each amino acid in the active region of the nanobody, the sequence that sheaths the viral spikes, and found one particular mutant that was 500 times stronger still than the best of those found in the database. However, the team did not stop there, they found, as with face masks with multiple layers of different fabrics, that they could boost efficacy still further by using three of the nanobodies simultaneously. Indeed, a 200,000 times boost was seen with this approach using any of the potent nanobodies, but when the most potent of all were combined, the effect was so strong that the team’s tests could not obtain a reading as it was “off the chart”, according to the researchers.

The researchers have named their technology AeroNabs, have applied for patents, and are now in discussions with commercial partners. In vivo tests, toxicity and other safety tests, and finally clinical trials will ultimately follow.