tetano
Editor, Senior Moderator
Virology. 2019 Apr 27. pii: S0042-6822(19)30109-6. doi: 10.1016/j.virol.2019.04.009. [Epub ahead of print]
[h=1]To hit or not to hit: Large-scale sequence analysis and structure characterization of influenza A NS1 unlocks new antiviral target potential.[/h] Trigueiro-Louro JM[SUP]1[/SUP], Correia V[SUP]2[/SUP], Santos LA[SUP]2[/SUP], Guedes RC[SUP]3[/SUP], Rebelo-de-Andrade H[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza NS1 protein is among the most promising novel druggable anti-influenza target, based on its structure; multiple interactions; and global function in influenza replication and pathogenesis. Notwithstanding, drug development guidance based on NS1 structural biology is lacking. Here, we design a promising strategy directed to highly conserved druggable regions as a result of an exhaustive large-scale sequence analysis and structure characterization of NS1 protein across human-infecting influenza A subtypes, over the past 100 years. We have identified 3 druggable pockets and 8 new potential hot spot residues in the NS1 protein, not described before, additionally to other 16 sites previously identified, which represent attractive targets for pharmacological modulation. This study provides a rationale towards structure-function studies of NS1 druggable sites, which have the potential to accelerate the NS1 target validation. This research also contributes to a deeper comprehension and insight into the evolutionary dynamics of influenza A NS1 protein.
Copyright ? 2019 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] Anti-influenza strategy; Consensus druggable pocket; Conservation; Druggability; Influenza; Non-structural protein 1
PMID: 31104825 DOI: 10.1016/j.virol.2019.04.009
[h=1]To hit or not to hit: Large-scale sequence analysis and structure characterization of influenza A NS1 unlocks new antiviral target potential.[/h] Trigueiro-Louro JM[SUP]1[/SUP], Correia V[SUP]2[/SUP], Santos LA[SUP]2[/SUP], Guedes RC[SUP]3[/SUP], Rebelo-de-Andrade H[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza NS1 protein is among the most promising novel druggable anti-influenza target, based on its structure; multiple interactions; and global function in influenza replication and pathogenesis. Notwithstanding, drug development guidance based on NS1 structural biology is lacking. Here, we design a promising strategy directed to highly conserved druggable regions as a result of an exhaustive large-scale sequence analysis and structure characterization of NS1 protein across human-infecting influenza A subtypes, over the past 100 years. We have identified 3 druggable pockets and 8 new potential hot spot residues in the NS1 protein, not described before, additionally to other 16 sites previously identified, which represent attractive targets for pharmacological modulation. This study provides a rationale towards structure-function studies of NS1 druggable sites, which have the potential to accelerate the NS1 target validation. This research also contributes to a deeper comprehension and insight into the evolutionary dynamics of influenza A NS1 protein.
Copyright ? 2019 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] Anti-influenza strategy; Consensus druggable pocket; Conservation; Druggability; Influenza; Non-structural protein 1
PMID: 31104825 DOI: 10.1016/j.virol.2019.04.009