LitCovid-sentences  

PMC:7291971 / 25171-28031 JSONTXT 9 Projects

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Id Subject Object Predicate Lexical cue
T184 0-48 Sentence denotes 2.5 Thermal shift DSF assays for SARS-CoV nsp14
T185 49-249 Sentence denotes SARS-CoV nsp14-inhibitor interactions were further investigated by monitoring the thermal stability of the protein using differential scanning fluorimetry (DSF) (Supporting Information, Fig. S3) [34].
T186 250-462 Sentence denotes The change in thermal stability of SARS-CoV nsp14 was monitored in response to binding of the natural cofactor substrate SAM, sinefungin and the 9 most active and specific compounds 6 and 9–16 with IC50 < 100 μM.
T187 463-672 Sentence denotes As expected, SARS-CoV nsp14 displayed an increased melting temperature (T m) value with SAM (+6.5 °C) and sinefungin (+4.4 °C) whose structure only differs by a C–NH2 in place of S+-CH3 group in SAM (Fig. 2 ).
T188 673-888 Sentence denotes The binding experiments with the bisubstrate inhibitors showed that all dinucleosides stabilized the SARS-CoV nsp14 protein (T m > 40 °C) with a T m shift from +4.6 °C to +10.8 °C (Supporting Information, Table S1).
T189 889-1023 Sentence denotes Eight of the 9 examined compounds increased the stability of SARS-CoV nsp14 more efficiently than the well-known inhibitor sinefungin.
T190 1024-1226 Sentence denotes More interestingly, T m values for SARS-CoV nsp14 were larger in the presence of five compounds 10 and 12–15 than with the natural enzyme substrate SAM, suggesting strong protein-inhibitor interactions.
T191 1227-1548 Sentence denotes Remarkably, the highest T m was observed with the most efficient inhibitor 13 (IC50 0.6 ± 0.1 μM) that stabilizes SARS-CoV nsp14 against thermal denaturation with a ΔT m +10.8 °C and exhibits notable binding affinity (apparent KD 1.3 ± 0.87 μM), as deduced from TSA performed with increasing concentration of compound 13.
T192 1549-1645 Sentence denotes This demonstrates a favorable interaction and highlights the inhibitor potential of compound 13.
T193 1646-1851 Sentence denotes The T m comparison of compounds 16, 15 and 13 showed a respective increase in SARS-CoV nsp14 stability, settling the importance of the sulfone group, the Cl and NO2 substituents in protein binding with 13.
T194 1852-1962 Sentence denotes Thus the N-(4-Cl-3-NO2-phenylsulfonamide) moiety is notably preferred for optimal SARS-CoV nsp14 interactions.
T195 1963-2168 Sentence denotes Another highlight is the thermal shift (+5.4 °C) for SARS-CoV nsp14 observed in the presence of compound 10 compared to 11, both only differ by the position of OCH3 and NO2 substituents in the phenyl ring.
T196 2169-2295 Sentence denotes A higher stability and inhibition of SARS-CoV nsp14 was observed when the OCH3 group is in “para” position in dinucleoside 10.
T197 2296-2429 Sentence denotes Fig. 2 Thermal shifts (ΔTm) of SARS-CoV nsp14 in the absence or presence of SAM, sinefungin and 9 dinucleoside inhibitors 6 and 9–16.
T198 2430-2537 Sentence denotes Thermal stability of SARS-CoV nsp14 upon ligand binding was monitored by differential scanning fluorimetry.
T199 2538-2738 Sentence denotes Assays were carried out in reaction mixture [20 mM HEPES (pH 7.5), 150 mM NaCl, 1x SYPRO orange dye] in the presence of 5 μM SARS-CoV nsp14 protein and 1 mM compound previously dissolved in 100% DMSO.
T200 2739-2860 Sentence denotes The bars and error bars correspond to the mean values from three independent measurements and their s.d.’s, respectively.