首页|NS1 protein as a novel anti-influenza target: Map-and-mutate antiviral rationale reveals new putative druggable hot spots with an important role on viral replication
NS1 protein as a novel anti-influenza target: Map-and-mutate antiviral rationale reveals new putative druggable hot spots with an important role on viral replication
扫码查看
点击上方二维码区域，可以放大扫码查看
原文链接
NSTL
Elsevier
Influenza NS1 is a promising anti-influenza target, considering its conserved and druggable structure, and key function in influenza replication and pathogenesis. Notwithstanding, target identification and validation, strengthened by experimental data, are lacking.Here, we further explored our previously designed structure-based antiviral rationale directed to highly conserved druggable NS1 regions across a broad spectrum of influenza A viruses.We aimed to identify NS1mutated viruses exhibiting a reduced growth phenotype and/or an altered cell apoptosis profile. We found that NS1 mutations Y171A, K175A (consensus druggable pocket 1), W102A (consensus druggable pocket 3), Q121A and G184P (multiple consensus druggable pockets) - located at hot spots amenable for pharmacological modulation -significantly impaired A(H1N1)pdm09 virus replication, in vitro. This is the first time that NS1-K175A,-W102A, and-Q121A mutations are characterized. Our map-and-mutate strategy provides the basis to establish the NS1 as a promising target using a rationale with a higher resilience to resistance development.
Antiviral strategyAntiviral targetDruggable pocketsInfluenza A virusNS1Viral replicationINFLUENZA-A-VIRUSEFFECTOR DOMAINVIRULENCEPATHWAYP85-BETASUBUNIT
Trigueiro-Louro, Joao、Santos, Luis A.、Almeida, Filipe、Correia, Vanessa、Brito, Rui M. M.、Rebelo-de-Andrade, Helena
展开 >
Universidade de Lisboa,Univ Lisbon
Instituto Nacional de Saude Dr. Ricardo Jorge,Inst Nacl Saude Doutor Ricardo Jorge IP
NSTL
Elsevier
