chuka_lis (chuka_lis) wrote,
chuka_lis
chuka_lis

Индометацин и коронавирус


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 properties12-14, 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.
Tags: коронавирус, статья
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