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Article

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

1
MetrioPharm Deutschland GmbH, Am Borsigturm 100, 13507 Berlin, Germany
2
Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
3
Meluna Research, Department of Biophotonics, Koppelsedijk 1A, 4191 LC Geldermalsen, The Netherlands
4
Institute of Virology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
5
MetrioPharm AG, Bleicherweg, 10 8002 Zurich, Switzerland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(22), 8803; https://doi.org/10.3390/ijms21228803
Received: 9 October 2020 / Revised: 18 November 2020 / Accepted: 19 November 2020 / Published: 20 November 2020
(This article belongs to the Special Issue COVID-19 and Molecular Studies in Biology and Chemistry)
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. View Full-Text
Keywords: COVID-19; SARS-CoV-2; oxidative stress; inflammation; cytokine storm; drug development; COVID-19 drugs COVID-19; SARS-CoV-2; oxidative stress; inflammation; cytokine storm; drug development; COVID-19 drugs
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MDPI and ACS Style

Schumann, S.; Kaiser, A.; Nicoletti, F.; Mangano, K.; Fagone, P.; van Wijk, E.; Yan, Y.; Schulz, P.; Ludescher, B.; Niedermaier, M.; von Wegerer, J.; Rauch, P.; Setz, C.; Schubert, U.; Brysch, W. 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. Int. J. Mol. Sci. 2020, 21, 8803. https://doi.org/10.3390/ijms21228803

AMA Style

Schumann S, Kaiser A, Nicoletti F, Mangano K, Fagone P, van Wijk E, Yan Y, Schulz P, Ludescher B, Niedermaier M, von Wegerer J, Rauch P, Setz C, Schubert U, Brysch W. 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. International Journal of Molecular Sciences. 2020; 21(22):8803. https://doi.org/10.3390/ijms21228803

Chicago/Turabian Style

Schumann, Sara, Astrid Kaiser, Ferdinando Nicoletti, Katia Mangano, Paolo Fagone, Eduard van Wijk, Yu Yan, Petra Schulz, Beate Ludescher, Michael Niedermaier, Joerg von Wegerer, Pia Rauch, Christian Setz, Ulrich Schubert, and Wolfgang Brysch. 2020. "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" International Journal of Molecular Sciences 21, no. 22: 8803. https://doi.org/10.3390/ijms21228803

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