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Comparative investigation of the efficacy of Cortexin®, Pineamine®, levilimab, adalimumab, and dexamethasone on cytokine storm models


A.V. Kalatanova(1), E.I. Trofimets(2), A.N. Afanasieva(1), V.B. Saparova(1), K.L. Kryshen(2), I.E. Makarenko(1) 1-ZAO «Pharm-Holding», 34A, Svyaz St., Strelna, Saint Petersburg 198515, Russian Federation; 2-PHARMACY HOUSE Research and Production Association, 245, Kuzmolovsky Settlement, Vsevolozhsky District, Leningrad Region 188663, Russian Federation

Introduction. During the coronavirus infection pandemic, there remains relevant to search for drugs that have a therapeutic effect on the cytokine storm as the main cause of complications in this disease in humans. Objective: to evaluate the efficiency of in vitro and in vivo administration of Cortexin® and Pineamine® versus levilimab, adalimumab, and dexamethasone against proinflammatory cytokines. Material and methods. In an in vitro experiment, a model of a lipopolysaccharide (LPS)-induced cytokine storm was created using the RAW 264.7 cell line, followed by measuring the level of TNFα in the culture medium. In an in vivo experiment, a murine model of septic shock was formed by a single intraperitoneal injection of LPS. The clinical condition and mortality of animals and their plasma level of proinflammatory cytokines IL-6 and TNFα were evaluated. Results. The in vitro study showed that Cortexin® and Pineamine® had a therapeutic effect on the level of TNFα in the culture medium. In the in vivo experiment, Cortexin® and Pineamine® decreased the severity of clinical signs of the disease and mortality in animals, exerted a therapeutic effect on IL-6 and TNFα levels in a cytokine storm, exceeding that for the comparison drug levilimab. Conclusion. Cortexin® and Pineamine® versus the comparison drug levilimab have shown a comparable or higher therapeutic activity in in vitro and in vivo models of cytokine storm. The results of the investigation and consideration of the safety profile and low cost of organic preparations have led to the conclusion that Cortexin® and Pineamine® are promising drug candidates for further design as an element of combination therapy or prevention of complications of diseases, the pathogenetic mechanism of which involves the overexpression of proinflammatory cytokines (including complications of the novel coronavirus infection COVID-19).

cytokine storm

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