Индометацин и коронавирус

[chuka_lis]

Индометацин показал противовирусный эффект в клеточной культуре, зараженной вирусом САРС2, и в экспериментах на собаках, инфицированных собачьим коронавирусом.

Surprisingly, indomethacin was found to possess a remarkable antiviral activity, reducing viral particle production dose-dependently with an IC50 (inhibitory concentration 50%) of 1 µM, and selective index of 500, and caused a dramatic reduction relative light unit to zero at 48 h p.i, in VERO E6 cells (Figure 1A). Oral administration of 50 mg of indomethacin generates a peak plasma concentration of the drug ranging from 7µM to 11µM, a concentration which is 10 times of the drug’s IC50

Аспирин не оказал никакого действия. Авторы предполагают, что индометацин влияет на репликаюцию вируса, а не оказывает эффект как противовоспалительное лекарство.

ndomethacin has been known to possess antiviral properties^12-14, and used for a long time as a potent anti-inflammatory drug, acting by blocking the activity of cyclooxygenase-1 and −2 (COXs), activity and inhibiting pro-inflammatory prostaglandin synthesis²³. Indomethacin reduces the synthesis of prostaglandin (PG) by inhibiting cyclooxygenase, and inhibiting the formation of painful nerve impulses in inflammatory tissues thus suppressing the inflammatory response¹⁰.In our experiments, we tested the COX inhibitors indomethacin and aspirin. Our results show that indomethacin has potent, direct antiviral activity against the SARS CoV-2 (reduce the relative light unit to zero) in VERO E6 cellsб while aspirin does not.
In our study of CCV-infected dogs, the results show that in items of anti-CCV efficacy, indomethacin can achieve a similar efficacy as treatment with anti-canine coronavirus serum, canine hemoglobin, canine blood immunoglobulin and interferon treatments effect (P =0.7784, Fig.2B), and superior efficacy than the treatment with ribavirin (P =0.0031, Fig.2A)
Although the underlying mechanism requires further investigation, the results of indomethacin anti-SARS-CoV show that indomethacin does not affect virus infectivity, binding or entry into target cells, but acts early on the coronavirus replication cycle, selectively blocking viral RNA synthesis¹². The only clear indomethacin antiviral mechanism is that, instead, triggers a cellular antiviral defense mechanism by rapidly and effectively activating PKR in an interferon- and dsRNA-independent manner¹³. PKR plays a critical role in the antiviral defense mechanism of the host, acting as a sensor of virus replication and²⁴, upon activation, leading to eIF2α phosphorylation and block of protein synthesis in virally infected cells²⁵.

Однако,  это в клеточной культуре, всего 2 дня после заражения, и с другим коронавирусом на собаках. Все же, вероятно, стоит провести больше исследований, чтоб разобраться.