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 severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic and the multi-organ coronavirus disease 2019 (COVID-19) are keeping a firm grip on the world. Although most cases are mild, older patients and those with co-morbidities are at increased risk of developing a cytokine storm, characterized by a systemic inflammatory response leading to acute respiratory distress syndrome and organ failure. The present paper focuses on the small molecule MP1032, describes its mode of action, and gives rationale why it is a promising option for the prevention/treatment of the SARS-CoV-2-induced cytokine storm. MP1032 is a phase-pure anhydrous polymorph of 5-amino-2,3-dihydro-1,4-phthalazinedione sodium salt that exhibits good stability and bioavailability. The physiological action of MP1032 is based on a multi-target mechanism including localized, self-limiting reactive oxygen species (ROS) scavenging activities that were demonstrated in a model of lipopolysaccharide (LPS)-induced joint inflammation. Furthermore, its immune-regulatory and PARP-1-modulating properties, coupled with antiviral effects against SARS-CoV-2, have been demonstrated in various cell models. Preclinical efficacy was elucidated in LPS-induced endotoxemia, a model with heightened innate immune responses that shares many similarities to COVID-19. So far, during oral clinical development with three-month daily administrations, no serious adverse drug reactions occurred, highlighting the outstanding safety profile of MP1032.

A Study on the Planarian Model Confirms the Antioxidant Properties of Tameron against X-ray- and Menadione-Induced Oxidative Stress

“…During this process, Tameron is oxidized, generating a photon emission that can be detected by sensitive photon-counting devices—for example, by the ultra-weak photon emission (UPE) method [ 39 ]. Tameron has been described as an antiviral agent [ 16 ], boosting the cellular antioxidant stress defenses after viral infection by activation and stabilization of the redox-sensitive NF-E2-related transcription factor 2 (Nrf2) [ 13 , 15 ], which can ameliorate the devastating impact of immune reactions on viruses, including cytokine storm [ 40 , 41 , 42 ]. Similar effects were observed for Tameron on a model of Gulf War illness—a neurological condition induced by chemical damage to brain tissue [ 12 ].…”

“…Its action mechanism involved the stabilization of the Nrf2 transcription factor, a known anti-inflammatory and antioxidant protein [ 15 ]. It was also tested on a mouse model and human peripheral blood mononuclear cells as an immunomodulatory agent for preventing cytokine storm, a devastating condition of the COVID-19 disease [ 16 ].…”

Oxidative DNA Damage-induced PARP-1-mediated Autophagic Flux Disruption Contributes to Bupivacaine-induced Neurotoxicity During Pregnancy

“…Currently, no promising treatment options are available against COVID-19 that can be recommended globally. Published studies have shown that PARP-1 inhibition limits inflammation-induced tissue damage, including acute lung injury in animal models, and PARP-1 inhibitors have therefore been discussed as a potential treatment option for COVID-19 [ 47 ].…”

Efficacy of MP1032 in hospitalised patients with COVID-19

“…Previous experiments demonstrated MP1032 is a drug with antiviral and immunomodulatory effects. 1 Recently, Petra Sager et al. further evaluated the efficacy and safety of MP1032 in hospitalized patients with moderate to severe COVID-19.…”