Old Drugs for JAK-STAT Pathway Inhibition in COVID-19

Abstract

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.