Repurposing Levocetirizine + Montelukast for the Treatment of COVID-19
An Acute Care Therapeutic to Decrease Inflammation / Decrease Morbidity and Mortality
Levocetirizine + montelukast (IRR401) as an acute care therapeutic has the potential to reduce the inflammatory response produced by COVID-19 (a ssRNA virus), systemically as well as in the lung, and to significantly decrease the probability of patients progressing from mild symptoms, to intubation, to death. Combination therapy has the ability to decrease pulmonary vascular resistance and improve cardiac output, underscored by improvement in FEV1 from 15-23% depending upon the dose and frequency of administration.
Levocetirizine + montelukast has the ability to safely attenuate the inflammatory response in end-stage COVID-19 patient, e.g., the viral cardiomyopathy preceding death. The addition of the combination therapy to the existing treatment paradigm will also mitigate adverse reactions (ADR’s) precipitated by other acute and critical care medications administered during the illness, e.g., antibiotics, vasopressors, anxiolytics, blood products (packed red blood cells, plasma, etc.).
Levocetirizine + montelukast a part of the COVID-19 treatment paradigm has the remarkable potential to safely and synergistically downregulate multiple signaling proteins, transcription factors, and cells within the inflammatory pathways in addition to the potential to exhibit clinically relevant antiviral activity.
The molecular science surrounding a COVID-19 combination therapeutic has continued to evolve over the past decade in a very favorable manner:
In the wake of an evolving lethal family of coronaviruses, the NIH in 2014, in conjunction with the United States Army Medical Research Institute of Infectious Disease, screened 290 compounds for antiviral activity. Only 27 drugs were active against both SARS-CoV (2002) and MERS-CoV (2012). The list included astemizole, a second-generation antihistamine. By analogy, levocetirizine, as one arm of a potential combination COVID-19 therapeutic, is safer, titratable, and more potent than astemizole.
Davino-Chiovatto, JE, et. al., found that montelukast efficiently attenuated LPS-induced lung inflammation in a mouse mode with ARDS (acute respiratory distress syndrome), research that parallels the clinical presentation found in critically ill COVID-19 patients.
Chen, et. al., reported on the in vivio and in vitro antiviral properties of montelukast alone against Zika virus, Dengue fever virus, and Yellow fever virus. Like COVID-19, all are ssRNA viruses.