LitCovid-sentences  

PMC:7291971 / 32286-34217 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T232 0-13 Sentence denotes 3 Conclusion
T233 14-166 Sentence denotes We synthesized 16 adenine dinucleosides which were designed as bisubstrate SAM analogs to mimic the transition state of 2′-O-methylation of the cap RNA.
T234 167-415 Sentence denotes Both adenosines were connected by various NH or N-substituted linkers between the 2′-O-position of the adenosine representing the 5′-end nucleoside of mRNA and the 5′-position of the adenosine mimicking the SAM cofactor in the methylation reaction.
T235 416-548 Sentence denotes None of these bisubstrate SAM analogs were found to inhibit 2′-O MTases of several flaviviruses, coronavirus or pox-virus at 200 μM.
T236 549-672 Sentence denotes Conversely, six of them inhibited SARS-CoV nsp14 N7-MTase in micromolar range concentration and one in submicromolar range.
T237 673-891 Sentence denotes Additionally, we also observed that these compounds barely inhibit the human RNA N7 MTase, an important feature given that the lack of antiviral specificity represents a common issue in coronavirus antiviral discovery.
T238 892-1026 Sentence denotes Indeed, the structural homology between viral and cellular MTases often impairs the discovery of specific inhibitors for CoV N7-MTase.
T239 1027-1325 Sentence denotes Nevertheless, our work did identify one dinucleoside (13) bearing a 4-chloro-3-nitrobenzenesulfonamide moiety in the N-linker between both adenosines, that blocks the activity of SARS-CoV nsp14 at the submicromolar concentration in the same range than sinefungin but with a significant specificity.
T240 1326-1489 Sentence denotes Thermal shift assays and molecular modeling indicate that the inhibitory activity is likely due to the binding of 13 to both SAM and mRNA binding pockets of nsp14.
T241 1490-1674 Sentence denotes It is quite interesting to note that all residues of SARS-CoV nsp14 involved in the binding of 13 are fully conserved in the SARS-CoV-2 nsp14 protein (Fig. S1, Supporting Information).
T242 1675-1787 Sentence denotes Indeed, the genome sequence of SARS-CoV-2 nsp14 exhibits about 95% sequence similarity with SARS-CoV nsp14 [38].
T243 1788-1931 Sentence denotes The lead compound 13 and the most potent derivatives will serve as starting building blocks for the development of SARS-CoV-2 nsp14 inhibitors.