An approach to inhibition of viral replication: inhibition of mRNA methylation.

Abstract

Several eukaryotic viral and cellular mRNAs contain at their 5′ terminus blocked methylated structures (often referred to as a “cap”) of the type m7GpppN′mpN″mp...(Fig. 1). Additional methylation of several mRNAs occurs internally between their 5′ cap and the 3′-poly(A) end, yielding 6-methyladenosine or 5-methylcytosine (Shatkin 1976). The 5′-terminal 7-methylguanosine in mRNAs is apparently required for their efficient translation in vitro (Both et al. 1975; Muthukrishnan 1978), and is also implicated in protection of mRNA against degradation by exonucleases. The enzymatic mechanisms involved in the synthesis of the cap structure have been worked out in detail by Moss and his co-workers with vaccinia virus (Moss et al. 1976) and by others (Furuichi et al. 1976). It involves (a) the transfer of a GMP residue from GTP to the 5′-diphosphate end of mRNA by GTP:mRNA guanylyltransferase to form the blocked structure GpppN..., (b) methylation of the 5′-terminal guanosine in the 7 position by mRNA (gua-nine-7-)-methyltransferase to form m7GpppN . . ., and (c) subsequent methylation of the penultimate nucleoside by mRNA(nucleoside-2′-)-methyltransferase to form m7GpppNm. All three enzymatic activities have been purified from vaccinia virus.KeywordsVaccinia VirusPolio VirusGuanine MethylatedVaccinia mRNABroad Spectrum Antiviral AgentThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.