Laboratory of Experimental Pharmacology (LAFE), Department of Physiology and Pharmacology, Biomedical Institute, Fluminense Federal University (UFF), Room 204-A, 24420-210 Niterói, RJ, Brazil.
Laboratory of Experimental Pharmacology (LAFE), Department of Physiology and Pharmacology, Biomedical Institute, Fluminense Federal University (UFF), Room 204-A, 24420-210 Niterói, RJ, Brazil.
Int Immunopharmacol. 2021 Mar;92:107336. doi: 10.1016/j.intimp.2020.107336. Epub 2020 Dec 28.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) that has emerged and rapidly spread across the world. The COVID-19 severity is associated to viral pneumonia with additional extrapulmonary complications. Hyperinflammation, dysfunctional immune response and hypercoagulability state are associated to poor prognosis. Therefore, the repositioning of multi-target drugs to control the hyperinflammation represents an important challenge for the scientific community. Cilostazol, a selective phosphodiesterase type-3 inhibitor (PDE-3), is an antiplatelet and vasodilator drug, that presents a range of pleiotropic effects, such as antiapoptotic, anti-inflammatory, antioxidant, and cardioprotective activities. Cilostazol also can inhibit the adenosine uptake, which enhances intracellular cAMP levels. In the lungs, elevated cAMP promotes anti-fibrotic, vasodilator, antiproliferative effects, as well as mitigating inflammatory events. Interestingly, a recent study evaluated antiplatelet FDA-approved drugs through molecular docking-based virtual screening on viral target proteins. This study revealed that cilostazol is a promising drug against COVID-19 by inhibiting both main protease (M) and Spike glycoprotein, reinforcing its use as a promising therapeutic approach for COVID-19. Considering the complexity associated to COVID-19 pathophysiology and observing its main mechanisms, this article raises the hypothesis that cilostazol may act on important targets in development of the disease. This review highlights the importance of drug repurposing to address such an urgent clinical demand safely, effectively and at low cost, reinforcing the main pharmacological actions, to support the hypothesis that a multi-target drug such as cilostazol could play an important role in the treatment of COVID-19.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）引起的 2019 年冠状病毒病（COVID-19）已经出现并在全球迅速传播。COVID-19 的严重程度与病毒性肺炎有关，还有其他肺外并发症。过度炎症、免疫功能失调和高凝状态与预后不良有关。因此，重新定位多靶点药物以控制过度炎症是科学界面临的重要挑战。西洛他唑是一种选择性磷酸二酯酶 3 抑制剂（PDE-3），具有抗血小板和血管扩张作用，具有多种多效作用，如抗凋亡、抗炎、抗氧化和心脏保护作用。西洛他唑还可以抑制腺苷摄取，从而提高细胞内 cAMP 水平。在肺部，升高的 cAMP 可促进抗纤维化、血管舒张、抗增殖作用，并减轻炎症事件。有趣的是，最近的一项研究通过对病毒靶蛋白进行基于分子对接的虚拟筛选，评估了抗血小板的 FDA 批准药物。这项研究表明，西洛他唑通过抑制主要蛋白酶（M）和 Spike 糖蛋白，是一种有前途的抗 COVID-19 药物，这加强了它作为 COVID-19 有前途的治疗方法的使用。考虑到 COVID-19 病理生理学的复杂性，并观察到其主要机制，本文提出了一个假设，即西洛他唑可能作用于疾病发展的重要靶点。这篇综述强调了药物再利用的重要性，以安全、有效和低成本的方式应对这一紧迫的临床需求，强调主要的药理作用，以支持这样一种假设，即西洛他唑等多靶点药物可能在 COVID-19 的治疗中发挥重要作用。
