With the COVID-19 pandemic continuing to rage on, researchers continue to hunt for therapies to treat the virus and its myriad associated symptoms. With a study titled “A Novel Strategy to Mitigate the Hyperinflammatory Response to COVID-19 by Targeting Leukotrienes” (published in peer-reviewed journal Frontiers in Pharmacology), a research team reveals a potential cause for one of more insidious conditions plaguing patients with severe COVID-19 cases.
The strategy is co-authored by Novateur Ventures founder and managing director Ali Ardakani and Colin Funk of Queen’s University in Kingston. It analyzes lipid mediators, or leukotrienes, as the cause behind the hyperinflammatory response found in severe cases, frequently leading to multi-organ dysfunction.
“Globally the race to develop new therapeutics or repurpose existing drugs to cultivate an effective therapeutic treatment for COVID- 19 is urgent; at Novateur, our research has been well underway since the first cases were discovered,” Ardakani said. “I am very pleased today to announce a strategy we believe can potentially impact COVID-19 patients in a safe and effective manner.”
Outsourcing-Pharma (OSP) recently discussed the study with Ardakani (AA), and what the implications of the study might be for future COVID-19 research and treatment.
OSP: Could you please how your researchers landed upon targeting leukotrienes as a strategy to deal with the hyperinflammatory response to COVID-19?
AA: Dr. Funk (co-author of the study and Scientific Lead at Novateur) has spent a large part of his career studying leukotrienes and their ability to induce inflammation. After researching the mechanism of COVID-19 and understanding the disease and studying multiple publications and case reports about the progression of disease severity in COVID-19, it became clear that these lipid mediators of inflammation could be intricately involved.
OSP: Could you please share what you feel are the highlights of the study?
AA: Leukotrienes are potent mediators of inflammation that promote the directed movement of certain white blood cells to active sites of infection/inflammation and induce vascular leakage. There is a hyperinflammatory response in patients with severe forms of COVID-19 that includes both of the steps above.
There are two generic drugs (Zyflo and Singulair) that block leukotriene synthesis and signal transduction that are used to treat inflammatory symptoms in mild-moderate asthmatics. These two drugs together could be used to potentially prevent the severe form of COVID-19; the drugs will only work before severe symptoms arise.
OSP: The study suggests a combination of two generics to treat COVID-19 patients. Could you please tell us a bit about the two drugs, and what are the benefits of using these particular drugs?
AA: Zyflo (zileuton) is a 5-lipoxygenase inhibitor. 5-Lipoxygenase initiates the synthesis of leukotrienes. Singulair (montelukast) is a leukotriene receptor antagonist (blocker).
By blocking the synthesis of leukotrienes, it should be feasible to stop all the inflammatory symptoms evoked by these lipid mediators. However, zileuton is a rather weak drug and requires twice a day dosing. If it were a better drug, in theory, only one drug in this class would be necessary.
Since montelukast blocks vascular leakage, is potent, and is only required once daily, this drug is ideal for blocking vascular leakage, preventing edema (fluid buildup) in the lungs and possibly also preventing viral dissemination into the vasculature where the virus causing COVID-19, SARS-CoV-2, wreaks havoc causing blood clots and injury to other organs in the body (heart, kidneys). The combination of both drugs would be best for treating COVID-19.
OSP: How do you see the findings of this study being applied and possibly leading down the road to an effective therapy for patients with the virus?
AA: There is a need to conduct a clinical trial, one that is randomized, double-blinded and placebo-controlled to see for sure if this hypothesis is valid. There are multiple inflammatory mediators in our bodies. Leukotrienes are one of many, so we need to assess their importance by blocking their formation and actions.
This trial should be started as soon as possible in a place where COVID-19 cases are high such as in the southern US.
OSP: What are the next steps?
AA: To prepare and launch a clinical trial to test the efficacy of this hypothesis on COVID-19 patients.