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Interferon in viral infection treatment. Broad-spectrum antivirals in COVID-19. (7)
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Your immunology work is renowned for discovery of the broad-spectrum antiviral medications. You study how interferon (a major immune molecule) helps to treat SARS, coronavirus, Ebola. Recently you research treatment for coronavirus COVID-19. How does interferon help to treat viral infections? Let me step back here and first of all say there is an incredible interest in finding therapies to treat coronavirus COVID-19 cases. And to find medications specifically targeting coronavirus COVID-19. What we’ve learned over many years of research is this. If you make what we call a pathogen-specific antiviral, it targets a facet of the virus. Viruses mutate so you might spend approximately two billion dollars bringing a drug to market. And I absolutely guarantee you that over time that virus will mutate to become resistant to that drug. So it’s not really a very appropriate approach to make a drug for every newly emerging pathogen. A better strategy might be to ask this question. What do we as the human host do to counteract infection? How do we clear viruses? It transpires that in response to any and all viruses, the very first thing we do Is this. In the context of an immune response we produce a soluble factor called interferon. It doesn’t matter what the virus is. It doesn’t matter where the virus targets. If it’s a respiratory virus like influenza or coronavirus COVID-19. If it’s a virus that you get through the mosquito bite, for example, Zika virus. If it’s a virus that infects through your your gastrointestinal system, through your mouth. It really doesn’t matter. We always mount that interferon response. Interestingly, viruses have co-evolved to encode their genomes factors that very specifically block that interferon production. So if nothing else that should tell us that that interferon response is very important. Because to survive interferon block viruses face problems. I’ve spent many decades working on understanding how interferon effectively inhibits virus replication. And we’ve learned that different stages of the virus replication cycle are affected by interferon treatment. Also interferons are very effective at boosting the immune response. So there’s a direct inhibition of different viruses. Interferon will target different viruses differently. At the same time interferon will boost the immune response to clear the virus. So knowing that we have a broad-spectrum antiviral medication. It doesn’t distinguish which virus it’s going to target. But broad-spectrum antiviral drug will be effective against all viruses. You can override the block that the virus puts on interferon production. You do it by treating with interferon. So we did this during the SARS outbreak in 2003 in Toronto. We treated patients in a hospital. We saw a rapid resolution of their lung pathology during the Ebola outbreak in West Africa. We treated patients in Guinea. Again we saw that there was an advantage of therapeutic benefit to treatment with interferon. Most recently with this new coronavirus COVID-19 SARS disease we also used interferon. We were fortunate to undertake an exploratory study in Wuhan, China. Again we looked at the effects of a therapeutic intervention with inhaled interferon. The preliminary data show us that perhaps we accelerated viral clearance from the upper respiratory tract. We also reduce some of inflammatory markers that are associated with the lung pathology in coronavirus COVID-19. So this has prompted us to move forward with randomized control trials. But the take-home message are that we have already good understanding of this broad-spectrum antiviral. We understand importance of interferon for clearing of virus. Because all viruses encode factors to block interferon production. So regardless of the virus, I would argue it’s important to consider interferon in that treatment strategy. You can use interferon in combination with other medications or as a sole agent. Interferon should be a consideration.When our clinical trial was undertaken in Wuhan it was of the peak of the coronavirus COVID-19 outbreak. The decision was made by the local authorities to use an inhaled interferon. You take the liquid interferon, you put it in a medicine cup. You do what’s called nebulizer treatment. You vaporize interferon. You use a mask to inhale the interferon. The downside of that method is a lot of the interferon is actually ingested. It is not necessarily directed into the lungs. So in the clinical trials that we propose the goal is to compare subcutaneous interferon, intravenous interferon, and another way to inhale interferon. This would ensure much more effective interferon delivery to the lungs. We don’t know the best route of interferon delivery. But that’s why one does randomized controlled clinical trials. We explore just that. That certainly applies to many other medications used in coronavirus COVID-19. There are so many case series. There are so many non-randomized clinical trials in coronavirus COVID-19. People report a treatment, then it gets hyped by the media. But it’s really really important to conduct the proper clinical trials. Often the results could be very different. Yes, that’s really important stuff. We did just an exploratory clinical trial. It suggests that there may be a therapeutic advantage of interferon in coronavirus COVID-19. But until we actually do the clinical trials, it’s early days. The point is that the World Health Organization has this huge trial. This global mega trial identified four specific therapeutic interventions. This trial includes interferon amongst them. So it was certainly based on our clinical studies that we published in 2003 in SARS epidemic. Because tour interferon clinical trials in SARS made people aware. It made the whole scientific community aware of the potential of interferon treatment for a coronavirus COVID-19. We will see now what results will show in the coming months.