Antiviral activity of merimepodib against foot and mouth disease virus in vitro and in vivo

Abstract

Foot and mouth disease virus (FMDV), a member of family Picornaviridae, belongs to the genus Aphthovirus, which causes foot and mouth disease (FMD), a highly transmissible disease that affects cloven-hoof animals. In spite of the fact that efficient vaccines are available, effective antiviral molecules for FMD are needed to reduce viral infection during early stages of infection. In this study, merimepodib was found to efficiently inhibit FMDV replication in a dose-dependent manner. The 50% inhibitory concentration (IC 50 ) of merimepodib antiviral activity against two distinct FMDV strains (O/MYA98/BY/2010 and A/GD/MM/CHA/2013) was estimated to be 7.859 and 2.876 μM, respectively, while the 50% cytotoxic concentration (CC 50 ) of merimepodib was found to be 47.74 μM. Furthermore, treatment with 30 μg merimepodib efficiently prolonged the survival time of suckling mice infected with FMDV. Taken together, these results suggested that merimepodib has the potential to be a novel antiviral agent against FMDV.

A highly sensitive cell-based luciferase assay for high-throughput automated screening of SARS-CoV-2 nsp5/3CLpro inhibitors

“…These molecules include merimepodib/VX-497, an inhibitor of the human inosine monophosphate dehydrogenase initially developed as an immunosuppressor ( Jain et al, 2001 ). Merimepodib was later found to have antiviral activity against several DNA and RNA viruses including HCV, Zika, Ebola and FMDV viruses ( Li et al, 2019 ; Marcellin et al, 2007 ; Markland et al, 2000 ; Tong et al, 2018 ). In the early phase of the COVID-19 pandemic, oral merimepodib was investigated in combination with intravenous remdesivir administration in a phase 2 clinical trial as a potential treatment for severe COVID-19.…”

A highly sensitive cell-based luciferase assay for high-throughput automated screening of SARS-CoV-2 nsp5/3CLpro inhibitors

“…These molecules include merimepodib/VX-497, an inhibitor of the human inosine monophosphate dehydrogenase initially developed as an immunosuppressor [45]. Merimepodib was later found to have antiviral activity against several DNA and RNA viruses including HCV, Zika, Ebola and FMDV viruses [46][47][48][49]. In the early phase of the COVID-19 pandemic, oral merimepodib was investigated in combination with intravenous remdesivir administration in a phase 2 clinical trial as a potential treatment for severe COVID-19.…”

Advanced Foot-And-Mouth Disease Vaccine Platform for Stimulation of Simultaneous Cellular and Humoral Immune Responses

“…Currently, FMD vaccine studies using an inactivated vaccine, modified virus inactivated vaccine (DIVA vaccine) [ 24 ], viral vector vaccine [ 25 ], adenovirus [ 26 , 27 , 28 ], virus-like particle (VLP) vaccine (bacterial) [ 29 ], baculovirus [ 30 , 31 ], plant-produced empty capsids [ 32 , 33 ], peptide vaccine (Poly(I:C)) [ 34 ], CpG [ 35 ], plant based recombinant vaccine (alfalfa [ 36 ], chloroplast of tobacco [ 37 ]), RNA vaccine [ 38 ], DNA vaccine (cDNA [ 39 , 40 ], electroporation [ 41 ], T cell [ 42 , 43 , 44 ], B cell [ 45 , 46 ] epitope, APC targeting [ 47 ]), live attenuated vaccine [ 48 , 49 , 50 , 51 ], and antiviral agent [ 52 , 53 ] are underway. However, no high-quality FMD vaccines that surpass the efficacy of the inactivated vaccine have been successfully developed to date.…”