Even though it’ll soon be a year since SARS-CoV-2 started wreaking havoc across the world, there is still no approved cure or vaccine for the COVID-19 infection. Cost-effective and efficient therapies for COVID-19 are urgently needed, especially seeing the recent surge in the number of new infections across the world.
While scientists and research institutes are still conducting thorough trials to develop vaccines, a group of researchers at the University of Pittsburgh School of Medicine may have found an effective therapeutic option to neutralise SARS-CoV-2 using llama nanobodies. llamas are domesticated animals from the camelid family and native to South America.
Neutralising antibodies, nanobodies and blocking COVID-19
This new study, published in the journal Science, starts by explaining why llama nanobodies may be very effective in treating COVID-19 patients. Like most coronavirus es, SARS-CoV-2 also expresses surface spike proteins or S proteins that use angiotensin-converting enzyme-2 (ACE2) receptors to gain entry into the human body. Investigations into the serum derived from recovering COVID-19 patients have shown the presence of potent neutralising antibodies (NAbs) that block the binding of S proteins with ACE2 receptors, thereby making the SARS-CoV-2 virus ineffective.
High-quality NAbs are therefore a potential method of blocking the novel coronavirus from infecting a human body – the reason why the plasma of recovered COVID-19 patients is so in demand all over the world right now. The research by Pitt scientists, on the other hand, uses llama nanobodies. Llama nanobodies, also known as VHH antibodies, are actually minimal and monomeric antigen-binding domains derived from llama antibodies. These nanobodies are tiny, highly soluble, stable, and can be readily bioengineered.
Deriving potent nanobodies from llamas
The study also suggests that since these llama nanobodies have strong and durable physicochemical properties, their stability can be utilised to produce low-cost and efficient inhalable therapeutics that can neutralize respiratory viruses like SARS-CoV-2.
To test if this can indeed be done, the researchers injected a black llama by the name of Wally with SARS-CoV-2 S proteins. Two months later, the scientists were able to isolate and derive the strongest nanobodies the llama’s body had produced using a mass spectrometry-based technique. These nanobodies were then injected into live SARS-CoV-2 samples at the Pittsburgh Centre for Vaccine Research. The researchers found that even a fraction of a nanogram of these llama nanobodies could neutralise enough of the SARS-CoV-2 virus to make it ineffective.
The researchers concluded that, to their knowledge, the llama nanobodies they isolated and used to eliminate their SARS-CoV-2 samples are the most potent neutraliser to date. They recommend that the flexible and efficient administration of these nanobodies through inhalation may further improve their antiviral efficacy, while at the same time this method would minimise the dose, cost and potential toxicity of the treatment as well. They further suggest that given the high sequence similarity between llama nanobodies and human immunoglobulins, the adoption of this method is likely to contribute immensely to curb the current pandemic as well as devise a potential therapy for any future outbreaks.
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