Heteromultivalent topology-matched nanostructures as potent and broad-spectrum influenza A virus inhibitors

被引:27
作者
Nie, Chuanxiong [1 ,2 ]
Stadtmueller, Marlena [2 ]
Parshad, Badri [1 ,3 ]
Wallert, Matthias [1 ]
Ahmadi, Vahid [1 ]
Kerkhoff, Yannic [1 ]
Bhatia, Sumati [1 ]
Block, Stephan [1 ]
Cheng, Chong [4 ]
Wolff, Thorsten [2 ]
Haag, Rainer [1 ]
机构
[1] Free Univ Berlin, Inst Chem & Biochem Organ Chem, Takustr 3, D-14195 Berlin, Germany
[2] Robert Koch Inst, Unit 17, Influenza & Other Resp Viruses, Seestr 10, D-13353 Berlin, Germany
[3] Univ Cambridge, Dept Chem Engn & Biotechnol, Cambridge CB3 0AS, England
[4] Sichuan Univ, Coll Polymer Sci & Engn, State Key Lab Polymer Mat Engn, Chengdu 610065, Peoples R China
基金
国家重点研发计划;
关键词
SUPPORTED LIPID-BILAYERS; INFECTION; NEURAMINIDASE; OSELTAMIVIR; HEMAGGLUTININ; NANOPARTICLES; RESISTANCE; SAFE;
D O I
10.1126/sciadv.abd3803
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Here, we report the topology-matched design of heteromultivalent nanostructures as potent and broad-spectrum virus entry inhibitors based on the host cell membrane. Initially, we investigate the virus binding dynamics to validate the better binding performance of the heteromultivalent moieties as compared to homomultivalent ones. The heteromultivalent binding moieties are transferred to nanostructures with a bowl-like shape matching the viral spherical surface. Unlike the conventional homomultivalent inhibitors, the heteromultivalent ones exhibit a half maximal inhibitory concentration of 32.4 +/- 13.7.g/ml due to the synergistic multivalent effects and the topology-matched shape. At a dose without causing cellular toxicity, >99.99% reduction of virus propagation has been achieved. Since multiple binding sites have also been identified on the S protein of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), we envision that the use of heteromultivalent nanostructures may also be applied to develop a potent inhibitor to prevent coronavirus infection.
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页数:9
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