Analgesics Candidates for JAK-STAT Pathway Inhibition as a Probable Treat for COVID-19, Bioinformatics Study

The pandemic threat of COVID-19 with more than 160 million cases and with about 5 percent critical cases characterized by cytokine storm and hyperinflammatory conditions. The disease more often leads to intensive care unit admission with a high rate of mortality. Janus kinase enzymes of Jak-1, Jak-2, Jak-3, and Tyk2 seem to be good targets for inhibition and cytokine storm management in these patients. In the present work, the binding ability and the probable inhibitory potential of different analgesics were studied by molecular docking to assess their applicability for clinical traits from different points of view. Our docking results indicated that naproxen, methadone, and amitriptyline considering their higher binding energy, lower variance in binding energy, and higher hydrophobicity, seem to express more inhibitory effects on Janus kinase enzymes than approved inhibitors for these enzymes, i.e. baricitinib and ruxolitinib. Accordingly, we suggest our wide list of candidate analgesics including indomethacin, etodolac, buprenorphine, rofecoxib, duloxetine, valdecoxib, naproxen, methadone, and amitriptyline for clinical assessments to investigate their tentative usefulness for COVID-19 treatment.