Ramatroban as a Novel Immunotherapy for COVID-19.

Abstract

SARS-CoV-2 virus suppresses host innate and adaptive immune responses, thereby allowing the virus to proliferate, and cause multiorgan failure, especially in the elderly. Respiratory viruses stimulate cyclooxygenase-2 (COX-2) to generate prostanoids including Prostaglandin D₂ (PGD₂) and thromboxane A₂. Furthermore, PGD₂ concentrations in the airways increase with aging. PGD₂ action mediated via DP₂ receptors suppresses both innate and adaptive immune responses, by inhibiting interferon-λ and stimulation of myeloid monocyte-derived suppressor cells respectively. PGD₂ and thromboxane A₂ actions via the TP receptors activate platelets leading to a prothrombotic state. Ramatroban, a small-molecule antagonist of DP₂ and TP receptors, reverses viremia-associated proinflammatory, immunosuppressive5 and prothrombotic processes which are similar to those induced by SARS-Cov-2. Ramatroban, used for the treatment of allergic rhinitis in Japan for the past 20 years has an excellent safety profile. Therefore, Ramatroban merits investigation as a novel immunotherapy for the treatment of COVID-19 disease.