In vitro antiviral efficacy of pleconaril and ribavirin on foot-and-mouth disease virus replication

Abstract

Antiviral therapy is a promising strategy to control acute viral infections. FMDV causes an acute infection and the vaccination provides a protective immunity 7 days post immunization. If the infection is uncontained, then it affects the entire herd. In such circumstances, if antiviral drug is administered the infection can be checked in a herd. Ribavirin is known to cure persistently infected BHK21 cells with FMD virus. However, there have been no systematic studies on antiviral activity of ribavirin against FMDV at different time points with the application of ELISA, PCR or real-time PCR. Pleconaril is known to inhibit enteroviruses and rhinoviruses but has not been explored on FMDV. Hence, the present study evaluates the in vitro antiviral efficacy of pleconaril and ribavirin on FMDV replication. The maximum non-toxic concentrations (MNTC) of pleconaril and ribavirin for BHK21 cells respectively were 7.81 lg/50 lL and 15.62 lg/50 lL. Thus, drug concentrations below MNTC were tested for their antiviral activity against serial tenfold diluted FMDV O, A and Asia 1 serotypes. Pleconaril did not inhibit FMDV serotype O replication at 7.5 lg/50 lL based on CPE inhibition assay and this was further confirmed using sandwich ELISA, PCR/real-time PCR. On the other hand, ribavirin at 15.62 lg/50 lL inhibited the in vitro replication of FMDV O, A and Asia 1 and the inhibition was confirmed by serotype specific sandwich ELISA, PCR and real-time PCR assays. The inhibition was directly proportional to the concentration of ribavirin. Therefore, ribavirin could be explored for its in vivo efficacy as a potential therapeutic in the prevention of early spread of FMDV infection in a herd.

Beyond the Magic of Moringa oleifera: Its Potential to Control Indonesian Serotype of Footand-Mouth-Disease Virus Replication through Inhibition of 3-Cysteine Protease

“…Based on binding affinity with the target protein 3CP, M. oleifera's bioactives exhibited a low energy affinity, ranging from -9.1 to -5.2 kcal/mol (Table 1). Several compounds also displayed lower binding affinities compared to Ribavirin, a standard therapy to inhibit FMDV replication [29]. Among all of the best performing compounds, Baicalin, Chlorogenic Acid, and Rutin served as the top three compounds with low binding affinity values at -9.1, -8.1, and -8.1 kcal/mol, respectively (Table 1).…”

“…Compounds were prepared by optimizing their conformations using Open Babel in PyRx 0.8 [28]. The inhibitor compound used as a positive control is Ribavirin, which is a drug that targets the 3C protease protein [29]. Molecular docking was performed using AutoDock Vina on PyRx 0.8 interface [30,31] with the protein treated as rigid structure and the compounds as the flexible entity [32].…”

Drug Repositioning for Hand, Foot, and Mouth Disease

“…Compared with monotherapy, combination drug therapy is also a promising strategy for treating virus infection. The combination uses of pleconaril and ribavirin have been reported against picornavirus, including type 1 diabetes-associated type B coxsackieviruses and foot and mouth disease [ 91 , 92 ]. Efavirenz, a non-nucleoside reverse transcriptase inhibitor, is widely used against HIV.…”