The Mode of Inhibition of TMV‐ and PVX‐Induced RNA‐Dependent RNA Polymerases by some Antiphytoviral Drugs

Abstract

Six nucleobase and nucleoside analogues (6‐aminouracil [6‐AU], 6‐aminothymin [6‐AT], 6‐fluorothymin [6‐FT], 2,4‐dioxohexahydro‐1,3,5‐triazine [DHT], 9‐(2,3‐dihydroxypropyl) adenine [DHPA] and 1‐β‐D‐ribofuranosyl‐1,2,4‐triazol‐3‐carboxamid [ribavirin]) with potential antiphytoviral activity were tested in an in vitro replication system for their effect on tobacco mosaic virus (TMV)‐and potato virus X(PVX)‐induced RNA dependent RNA polymerase. 6‐AU, 6‐AT, 6‐FT, and DHPA inhibited both polymerases which may be a target of these compounds. A Putative noncompetitive mode of inhibition is discussed. Whereas ribavirin did not affect the in vitr RNA synthesis in the established systems, the uracil‐derivative DHT inhibited only the PVX‐specific enzyme.

Selective chemotherapy on Grapevine leafroll-associated virus-1 and -3

“…The therapeutic effect of RB on grapevines infected by GLRaV-3 was very low compared with other published results (Barba et al 1990;Guta et al 2010), probably due to the use of variant plant material. Effects of IMPDH or purine biosynthesis inhibitors on efficient virus eradication from infected grapevine could be through inhibiting viral nucleic acid replication, as reported for RB (Lozoya-Saldana et al 1984) or nucleobase or nucleoside analogues (Schulze and Kluge 1994) administration in plants. Otherwise, mechanism of action of neuraminidase inhibitor in plants is unknown, even if high sanitation rates reported in this paper confirm the effectiveness of OS reported by Guta et al (2010).…”

Review. Elimination of viruses in plants: twenty years of progress

“…The inhibition of replication of TMV was reported using nucleobase or nucleoside analogues (Schulze & Kluge, 1994), bitriazolyl compounds (Xia et al, 2006), tylophorine B (Xi et al, 2006), and derivatives of thiadiazoleacetamide (Zhao et al, 2006). Several groups of antiviral drugs, that have shown significant therapeutic potential against plant viru-ses, belong to inosine monophosphate dehydrogenase (IMPDH) inhibitors, S-adenosylhomocysteine hydrolase (SAH) inhibitors, neuraminidase (NA) inhibitors.…”

“…In fact, the principal target of antiviral activity of these molecules is the inosine monophosphate dehydrogenase, an enzyme that catalyzes the conversion of inosine 5'-monophosphate (IMP) in xantosine 5'-monophosphate and is able to alter the pathway for the production of guanosine mono-di-and triphosphate. The presence of its inhibitor acts on this Weiland et al, 2004;Panattoni et al, 2006Panattoni et al, , 2007aSkiada et al, 2009bJames et al, 1997;Cieslinska, & Zawadzka, 1999;Cieslinska, 2002;O'Herlihy et al, 2003Janeckova, 1993Gabova, 1995;Chen & Li, 2001;Chen & Lu, 2000Kolbanova et al, 2004Iwanami & Ieki, 1994Cieslinska, 2003Conrad, 1991Green et al, 1992;Park et al, 1994;Kim et al, 1996;Truskinov & Rogozina, 1997;Faccioli & Zoffoli, 1998;Horackova, 1998;Nascimento et al, 2003;Fang et al, 2005Loi et al, 1991Schulze & Kluge, 1994Kim et al, 1994Xu & Niimi, 1999;Xu et al, 2000Ram et al, 2005Bertaccini et al, 2004Ramírez-Malagón et al, 2006Xu et al, 2004Lim et al, 1993;Toussaint et al, 1993;Fletcher et al, 1998;Freitas & Rezende, 1998;Yap et al, 1999;Fletcher & Fletcher, 200...…”

An X-ray crystallographic study of C-5 and C-6 substituted 1,3-dimethyl-6-aminouracil architectures

“…AZT, DDI, DDC, BVDU), there is a renewed interest in the synthesis and design of heteroaromatic species of uracil origin having biological significances [9]. Several patents have been reported describing the synthesis of such heterocycles, derivatives of which are useful as vasodilators, bronchodilators [10], antiallergic [10,11], antihypertensive [12,13], antiphytoviral drugs [14] and anticancer [10] agents. Many drug candidates have been modeled on these compounds, particularly for cancer and virus research.…”