Study of Ruxolitinib Plus Simvastatin in the Prevention and Treatment of Respiratory Failure of COVID-19.

Summary

COVID-19's mechanism to enter the cell is initiated by its interaction with its cellular receptor, the angiotensin-converting enzyme. As a result of this union, a clathrin-mediated endocytosis process begins. This route is one of the therapeutic targets for which available drugs are being investigated in order to treat COVID-19 infection. This is one of the mechanisms blocked by drugs like ruxolitinib and chloroquine. Various drugs approved for clinical use that block the clathrin-mediated endocytosis pathway have been explored. It has been found that the best in vitro and in vivo results were obtained with statins, which also allowed generating a greater potent adaptive immune response. Therefore, statins and specifically simvastatin make it possible to block the entry process used by COVID-19, block inflammation by various mechanisms and increase the adaptive immune response. All of these processes are desirable in patients infected with COVID-19. Statins have been proposed to have beneficial effects in patients infected with MERS-COV, another coronavirus similar to COVID-19, but there have been no randomized studies supporting the use of statins in patients with COVID-19 infection. In this project we propose the combined use of one of these drugs, ruxolitinib with simvastatin, looking for a synergistic effect in the inhibition of viral entry and in the anti-inflammatory effect.

Timeline

Start

2020-04-12

Primary completion

2021-01-31

Completion

2021-01-31

Publications

• Garcia-Donas J, Martinez-Urbistondo D, Velazquez Kennedy K, Villares P, Barquin A, Dominguez A, Rodriguez-Moreno JF, Caro E, Suarez Del Villar R, Nistal-Villan E, Yague M, Ortiz M, Barba M, Ruiz-Llorente S, Quiralte M, Zanin M, Rodriguez C, Navarro P, Berraondo P, Madurga R. Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution. Front Immunol. 2023 Apr 18;14:1156603. doi: 10.3389/fimmu.2023.1156603. eCollection 2023.
• Sultana J, Crisafulli S, Gabbay F, Lynn E, Shakir S, Trifiro G. Challenges for Drug Repurposing in the COVID-19 Pandemic Era. Front Pharmacol. 2020 Nov 6;11:588654. doi: 10.3389/fphar.2020.588654. eCollection 2020.

Drugs

Indications