The three-dimensional (3D) structure of Foot-and-Mouth Disease Virus (FMDV) RNA-dependent RNA polymerase (RRp) makes it possible to design its (RRp) inhibitors. Development of such agents will be useful in reducing the excretion of FMDV from infected pigs. The FMDV RRp was expressed by a Bac-toBac baculovirus expression system and was purified by affinity chromatography with Ni Sepharose. The 3D structure of FMDV RRp was estimated by software using basic data from an X-ray analysis of crystallized Poliovirus RRp. Since the 3D structure of RRp is known to have the same shape as other polymerases, Efavirenz, one of the non-nucleotide Reverse Transcriptase inhibitors of anti-HIV agents and T-1105, one of the Pyrazinecarboxamide derivatives, were selected as anti-FMDV agents. The antiviral activities of Efavirenz and T-1105 were determined to be 20-40μg/ml and 1.6μg/ml, respectively, by means of a 50% plaque reduction assay with FMDV O/JPN/2000.
(Research Team for Exotic Diseases, TEL +81-42-321-1441)
Reference:
Sakamoto et al. (2006) JARQ 40 : 271-276.
