Inhibition of host inosine monophosphate dehydrogenases 1 and 2 (IMPDH1, IMPDH2) and subsequent depletion of cellular GTP pools is proposed to be a mechanism of action of IMPDH inhibitors (ribavirin, thioguanine, mycophenolic acid). IMPDH tetramers catalyzes the rate-limiting step where inosine 5′-monophosphate is converted to xanthine monophosphate during guanosine monophosphate (GMP) synthesis. GMP is later converted to guanosine triphosphate (GTP). IMPDH inhibitors mimic inosine 5′-monophosphate and act as competitive inhibitors of IMPDH (Nelson et al. 1990, Vethe et al. 2008, Elgemeie 2003, Te et al. 2007). Inhibited de novo synthesis of guanine nucleotides and decreased intracellular GTP pools leads to a decline in viral protein synthesis and limit replication of viral genomes (Mori et al. 2011).
Bremer, S, Bergan, S, Vethe, NT
Allison, AC, Nelson, PH, Wang, CC, Eugui, E
Ariumi, Y, Dansako, H, Kato, N, Ikeda, M, Wakita, T, Mori, K
Te, HS, Randall, G, Jensen, DM
Elgemeie, GH
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