ML390 inhibits enterovirus 71 replication by targeting de novo pyrimidine biosynthesis pathway

Enterovirus 71 (EV71), a little, single-stranded, positive-sense RNA virus of the enterovirus genus in the household Picornaviridae, causes hands, feet, and mouth disease. Although EV71 seriously threatens to public health, no effective antiviral drugs are for sale to treating this ailment. Within this study, we discovered that ML390, a dihydroorotate dehydrogenase inhibitor, has potential anti-EV71 activity. ML390 dose-dependently inhibited EV71 replication with IC50 and selectivity index values of .06601 ┬ÁM and 156.5, correspondingly. The use of the downstream product orotate considerably covered up ale ML390 to hinder EV71 replication. Furthermore, an sufficient way to obtain exogenous uridine and cytosine covered up the anti-EV71 activity of ML390. Thus, the antiviral activity of ML390 is mediated through the inhibition from the pyrimidine synthesis path. Within an EV71-infected mouse model, ML390 reduced the burden of EV71 within the brain, liver, heart, spleen, front legs, and hind legs, and considerably elevated the rate of survival from the rodents infected by EV71. ML390 shows potential to treat hands, feet, and mouth disease brought on by EV71 infection.

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