Immune modulating drug MP1032 with SARS-CoV-2 antiviral activity in vitro: A potential multi-target approach for prevention and early intervention treatment of COVID-19

Abstract

At least since March 2020, the multiorgan disease COVID-19 has a firm grip on the world. Although most of the cases are mild, patients from risk populations could develop a cytokine storm, which is characterized by a systemic inflammatory response leading to acute respiratory distress syndrome and organ failure. The present paper will introduce the small molecule MP1032, describe its mode of action, and give rationale why it is a promising option for prevention/treatment of SARS-CoV-2-induced cytokine storm. MP1032 is a phase-pure anhydrous polymorph of 5-amino-2,3-dihydro-1,4-pthalazinedione sodium salt that exhibits good stability and bioavailability. The physiological action of MP1032 is based on a multi-target mechanism including localized, self- limiting antioxidant activities that were demonstrated in a model of lipopolysaccharide (LPS)-induced joint inflammation. Furthermore, immune-regulatory and PARP-1 modulating properties, coupled with antiviral effects against SARS-CoV-2 were shown in various cell models. Efficacy has been preclinically elucidated in LPS-induced endotoxemia, a model with excessively activated immune responses that shares many similarities to COVID-19. So far, during oral clinical development with three-months daily administrations, no serious adverse drug reactions occurred highlighting the outstanding safety profile of MP1032.

Intravenous immunoglobulin as an important adjunct in the prevention and therapy of coronavirus 2019 disease

“…As the mechanisms might suggest, one of the strongest targets for therapy could be aberrant immune response and cytokine-mediated inflammation, manageable with corticosteroids, passive immunization, immunotherapies -such as neutralizing antibodies to IL-6 and recombinant IL-1 receptor antagonist -convalescent plasma and intravenous immunoglobulin (IVIg). [10][11][12] Although immunosuppression might be a suggested solution, immunomodulation through IVIg offers a lower exposure to adverse effects and a safer therapeutic mechanism.…”

“…Even with the current understanding of new pathogenic mechanisms, questions remain what the specific pharmacological objective is. As the mechanisms might suggest, one of the strongest targets for therapy could be aberrant immune response and cytokine‐mediated inflammation, manageable with corticosteroids, passive immunization, immunotherapies – such as neutralizing antibodies to IL‐6 and recombinant IL‐1 receptor antagonist – convalescent plasma and intravenous immunoglobulin (IVIg) 10‐12 …”