论文标题
COVID-19
Old Drugs for JAK-STAT Pathway Inhibition in COVID-19
论文作者
论文摘要
Covid-19的大流行威胁，有超过3700万例病例，其中约有5％进入以细胞因子风暴和过度炎症状态为特征的关键阶段，该州常常导致死亡率迅速的重症监护病房。 JAK-1，JAK-2，JAK-3和TYK2的Janus激酶酶似乎是药物抑制在这种情况下控制细胞因子风暴的良好靶标。在目前的工作中，研究了不同镇痛药对这些靶标的抑制性能，以评估其从不同角度使用临床应用的能力。我们的对接结果表明，考虑到其较高的结合能，较低的能量方差和较高的疏水性，萘普生，美沙酮和阿米替林似乎对Janus激酶酶表达了比对批准的抑制剂（即Bariticinib和ruxolitinib）更大的抑制作用。因此，我们建议我们的广泛候选药物清单，包括吲哚美辛，雌激素，丁丙诺啡，Rofecoxib，Duloxetine，Valdecoxib，Valdecoxib，naproxen，chadadone和Amitriptilin和Amitriptilin对临床评估，以便在COVID-19治疗中有用，尤其是对现在的病例，对此有所批准。
The pandemic threat of COVID-19 with more than 37 million cases in which about 5 percent entering critical stage characterized by cytokine storm and hyperinflammatory condition, the state more often leads to admission to intensive care unit with rapid mortality. Janus kinase enzymes of Jak-1, Jak-2, Jak-3, and Tyk2 seem to be good targets for inhibition by medications to control cytokine storm in this context. In the present work, the inhibitory properties of different analgesic drugs on these targets are studied to assess their ability for clinical application from different points of view. Our docking results indicated that naproxen, methadone, and amitriptyline considering their higher binding energy, lower energy variance, and higher hydrophobicity, seem to express more inhibitory effects on Janus kinase enzymes than thats for approved inhibitors i.e. baricitinib and ruxolitinib. Accordingly, we suggest our wide list of candidate drugs including indomethacin, etodolac, buprenorphine, rofecoxib, duloxetine, valdecoxib, naproxen, methadone, and amitriptilin for clinical assessments for their usefulness in COVID-19 treatment, especially taking into account that up to now, there is no approved cure for this disease.
