LitCovid-sentences  

PMC:7291971 / 5993-7814 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T42 0-275 Sentence denotes With the aim of enhancing specificity of MTase inhibitors, we developed an approach of bisubstrate inhibitors that display a suitable linker between two adenosines that mimic the transition state of the methyl transfer reaction at 2′-O position of the RNA cap structure [12].
T43 276-399 Sentence denotes One adenosine is supposed to target the SAM binding site and another adenosine would target the RNA binding site (Fig. 1 ).
T44 400-536 Sentence denotes Recently, we described the synthesis of a first series of bisubstrate adenine dinucleosides with various sulfur-containing linkers [14].
T45 537-723 Sentence denotes Unexpectedly, such compounds tested at 50 μM or 200 μM concentration failed to inhibit several RNA 2′O-MTases of SARS-CoV, Zika, West Nile, Dengue and Pox viruses such as vaccinia virus.
T46 724-894 Sentence denotes Their potential of inhibition toward N7-MTases of SARS-CoV and vaccinia virus was also explored and none of the S-linked dinucleosides was active against these N7-MTases.
T47 895-1025 Sentence denotes From these data, in the present work we replaced the sulfur atom (S) by a nitrogen atom (N) in the linker between both adenosines.
T48 1026-1272 Sentence denotes This modification presents the advantage of increasing the chemical stability of the linker and offers a possible variability of compounds due to the N-substitution by any chain susceptible to interact with additional protein residues (Scheme 1).
T49 1273-1485 Sentence denotes It is noteworthy that bisubstrate dinucleosides with N-containing linkers have already been reported in transition state analogs of DNA methylation [15] and of RNA methylation at N6 position of adenosine [16,17].
T50 1486-1599 Sentence denotes However, till our work, none viral 2′O-MTase or N7-MTase have been targeted by bisubstrate adenine dinucleosides.
T51 1600-1712 Sentence denotes This observation led us to explore the impact of N-linkers on the antiviral activity of bisubstrate SAM analogs.
T52 1713-1821 Sentence denotes Fig. 1 Rationale for designing a library of bisubstrate compounds for targeting RNA 2′-O-methyltransferases.