Alfacyte: the surprise protein that could train the immune system to fight coronavirus

In anticipation of an effective vaccine, the challenge of finding Covid-19 treatments has proven to be considerable. And while there are encouraging signs that a vaccine could be on the way with the latest Pfizer/BioNTech trials, it will still take time for this to reach all those who need it most.

In the meantime, an 11,000-patient trial conducted by the WHO last month has yielded disappointing results that cast doubts on the efficacy of the Remdesivir drug in helping patients with severe illness caused by the SARS-CoV-2 virus.

Still, the hunt goes on, undeterred, for better treatments to combat the most severe Covid infections. Among the range of possible remedies are a set of proteins called “interferons”. Occurring naturally in the human body, these immune-signalling molecules are suppressed by the coronavirus when it attacks the body.

The WHO trial examined one such interferon, beta 1a, and found that use had “little to no effect” on patient mortality. But Professor Bill Stimson, chief scientific officer at ILC Therapeutics in Lanarkshire, Scotland, has engineered an interferon-led fightback. His labs have developed an artificial interferon, Alfacyte, which is at least fifteen times more effective at fighting the virus than beta 1a.

“No, Alfacyte wasn’t intended for Covid-19 specifically”, Stimson tells Reaction. “We didn’t know that it would be active against Covid-19 until I gave it to Catherine Adamson [at the School of Biology at the University of St. Andrews]. She tried it and went ‘Wey-hey!’, and I said, ‘Do it again!’, and she said ‘Wey-hey!’, and I said, ‘Do it again!’”

Multiple experiments comparing Alfacyte with natural interferons confirmed the results, announced last month. But Dr Catherine Adamson, who ran the tests, warns us not to get too excited. “There are always more experiments to do”, and clinical trials early next year will be the true test of Alfacyte’s efficacy as a treatment.

What is striking about the results, however, is their debt to one of science’s (informal) founding doctrines – “have a go and see what happens”.

Professor Stimson and his team had been experimenting with natural interferons for over twenty years, to produce something that could fight respiratory viruses like HIV and SARS. “What we’ve been doing is looking at the structure of the molecule and altering it, trying to see how we can enhance various gene responses and diminish other gene responses.”

Those years of chemical re-engineering now seem to have paid off – thanks to the opportunity presented by the category 3 laboratories at the University of St. Andrews, about a 90-minute drive away.

“I wasn’t particularly primed by the company, in terms of what to expect [from Alfacyte]”, says Dr Catherine Adamson, who put her name forward to take on the experiments. “It was a simple case of being given the test samples and having a go.”

Have a go they did – and Alfacyte seems to be a proven viral inhibitor. “This interferon does a lot more than just kill the virus”, Stimson says, comparing the agent to popular treatments like Remdesivir. “It prepares the environment of the tissue and helps to regenerate it… [and] activates a series of cytokines which activate both the innate and the adaptive immune responses.”

Further experiments could determine if a combination of Alfacyte and Remdesivir produces an enhanced anti-viral effect in cell culture. Stimson hopes that, pending clinical trials, a “cocktail” drug administered by aerosol could strengthen the immune response in patients before early after diagnosis.

Covid-19 threatens vulnerable patients by blocking the release signalling proteins such as interferons, which trigger the immune response. The immune system later over-compensates, triggering a “cytokine storm” which endangers vital organs, seriously threatening the patient’s life.

Now that Alfacyte’s Eureka moment has passed, the next stage begins: the painstaking process of trial-and-error that will accompany animal and human trials over the coming months. But we can at least take solace in the knowledge that, amid the frustration and disappointment of our current situation, the imperative of scientific enquiry remains solid: “have a go”. Wey-hey.