PMC:7600245 / 45713-47805
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7600245","sourcedb":"PMC","sourceid":"7600245","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7600245","text":"Considering activity against coronaviruses, in vitro studies demonstrated that indomethacin has a potent direct antiviral activity against the SARS coronavirus as determined in monkey Vero E6 cells and human lung epithelial A549 cells as well as against the canine coronavirus as determined in A72 canine cells. Indomethacin blocked the viral RNA synthesis, but not the viral adhesion/entry into the host cells. This effect is independent of the cyclooxygenase inhibition. At a dose rate of 1 mg/kg, indomethacin resulted in more than 1000-fold reduction in the virus yield in coronavirus-infected dogs [143]. Likewise, indomethacin has been reported to be a potent inhibitor of SARS CoV-2 replication in Vero E6 cells with an IC50 value of 1 µM, which is 10-fold less than its peak plasma concentration, and a selective index of 500-fold. Using a dose of 1 mg/kg in canine coronavirus-infected dogs, indomethacin accelerated the symptoms relieve and saved all infected animals, relative to ribavirin or anti-canine coronavirus serum/canine hemoglobin/canine blood immunoglobulin/INF regimen [144]. Previously, indomethacin also showed antiviral activity against rotavirus infection and vesicular stomatitis virus infection [145,146]. The antiviral activity of indomethacin was proposed to be a result of its binding to peroxisome proliferator activated receptor-γ, aldose reductase, and/or the viral NSP7/NSP8 complex [144]. The inhibition of the NSP7/NSP8 complex has been relatively verified and happened by indomethacin potentially targeting the interface between the host prostaglandin E synthase 2 and the viral NSP7/NSP8. In fact, prostaglandin E synthase 2 itself is inhibited by indomethacin in Vero cells with an IC50 value of 750 nM [144]. Lastly, in addition to the inhibition of the pro-inflammatory prostaglandin biosynthesis, indomethacin was also found to halt the increase in IL-6 expression caused by lipopolysaccharide-treated U937 cells [147]. 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