The IMPDH inhibitors, ribavirin and mycophenolic acid, inhibit peste des petits ruminants virus infection
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Peste des petits ruminants virus (PPRV) causes highly contagious diseases in domestic and particular wild small ruminants, leading to substantial economic loss. The development of effective and cheap antiviral medications shall help to circumvent this emerging burden. In this study, we found that ribavirin, a competitive inosine-5’-monophosphate dehydrogenase (IMPDH) inhibitor, significantly inhibits the replication of PPRV. As IMPDH is a key enzyme in purine nucleotide synthesis, supplementation of exogenous guanosine attenuate the anti-PPRV effect of ribavirin. Interestingly, an uncompetitive IMPDH inhibitor, mycophenolic acid (MPA), exerted more potent antiviral effect again PPRV. Similarly, this effect was largely restored upon supplementation of guanosine. Thus, we have demonstrated that the IMPDH inhibitors ribavirin and MPA combat PPRV infection through purine nucleotide depletion. Because both regimens have been widely used in the clinic for treating viral infection or organ rejection in transplantation patients for decades, respectively, repurposing these existing safe and cheap medications may provide a new avenue for combating PPRV infection.
The authors would like to thank Dr. Qiuwei Pan (Erasmus MC-University Medical Center) for helpful technical assistance. This study was funded by Key science and Technology Foundation of Gansu Province (1504WKCA094), Characteristic discipline of bioengineering construction for the special guide project of the world class universities and world-class disciplines of Northwest Minzu University(10018703), and National Natural Science foundation of China (No.31302100).
Compliance with ethical standards
In this study, all experiments have carried out without any humans or animals.
Conflict of interest
All authors have no conflict of interest in this study.
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