tetano
Editor, Senior Moderator
J Biomol Struct Dyn. 2019 Oct 15:1-10. doi: 10.1080/07391102.2019.1680436. [Epub ahead of print] [h=1]Structure-based methoxyflavone derivatives with potent inhibitory activity against various influenza neuraminidases.[/h]
Zang Y[SUP]1[/SUP], Hao D[SUP]1[/SUP], Wang H[SUP]1[/SUP], Yang Z[SUP]1,[/SUP][SUP]2[/SUP], Liu H[SUP]2[/SUP], Zhang S[SUP]1[/SUP].
[h=3]Author information[/h] 1 School of Science, MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, Xi'an Jiaotong University , Xi'an 710049, China. 2 School of Life Science and Technology, Xi'an Jiaotong University , Xi'an 710049, China.
[h=3]Abstract[/h] Inhibition of neuraminidase has been considered as a promising way for the treatment of influenza. While the significant resistance to available commercial drugs highlights the development of new antiviral compounds and novel immunomodulatory agents. In this work, we studied a series of methoxyflavone (MF) analogues in contrast to the existing neuraminidase inhibitors (NAIs). The results revealed that the top 4 compounds share a couple of common functional groups of MF, and their binding patterns seem to be comparable to the case of oseltamivir, with some distinct binding profiles. Compound 7, with the replacement of carboxyl and guanidino groups at R7 and R5 of MF, presents the highest interaction energy among the selected derivatives. The molecular mechanics/generalized Born surface area (MM-GBSA) analysis further revealed that compound 7 has stronger nonpolar interactions in contrast to those of oseltamivir, with weaker polar interactions. What's more, compound 7 exerts tolerable binding affinities across the oseltamivir-resistant mutants, and binds well with various neuraminidases. Therefore, compound 7 should be an ideal lead compound with the potential broad-spectrum activities. We hope that these results are benefit for the development of next generation anti-influenza drugs.
PMID: 31612780 DOI: 10.1080/07391102.2019.1680436
Zang Y[SUP]1[/SUP], Hao D[SUP]1[/SUP], Wang H[SUP]1[/SUP], Yang Z[SUP]1,[/SUP][SUP]2[/SUP], Liu H[SUP]2[/SUP], Zhang S[SUP]1[/SUP].
[h=3]Author information[/h] 1 School of Science, MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, Xi'an Jiaotong University , Xi'an 710049, China. 2 School of Life Science and Technology, Xi'an Jiaotong University , Xi'an 710049, China.
[h=3]Abstract[/h] Inhibition of neuraminidase has been considered as a promising way for the treatment of influenza. While the significant resistance to available commercial drugs highlights the development of new antiviral compounds and novel immunomodulatory agents. In this work, we studied a series of methoxyflavone (MF) analogues in contrast to the existing neuraminidase inhibitors (NAIs). The results revealed that the top 4 compounds share a couple of common functional groups of MF, and their binding patterns seem to be comparable to the case of oseltamivir, with some distinct binding profiles. Compound 7, with the replacement of carboxyl and guanidino groups at R7 and R5 of MF, presents the highest interaction energy among the selected derivatives. The molecular mechanics/generalized Born surface area (MM-GBSA) analysis further revealed that compound 7 has stronger nonpolar interactions in contrast to those of oseltamivir, with weaker polar interactions. What's more, compound 7 exerts tolerable binding affinities across the oseltamivir-resistant mutants, and binds well with various neuraminidases. Therefore, compound 7 should be an ideal lead compound with the potential broad-spectrum activities. We hope that these results are benefit for the development of next generation anti-influenza drugs.
PMID: 31612780 DOI: 10.1080/07391102.2019.1680436