title: DNA-AuNP networks on cell membranes as a protective barrier to inhibit viral attachment, entry and budding.
abstract: Viral infections have caused numerous diseases and deaths worldwide. Due to the emergence of new viruses and frequent virus variation, conventional antiviral strategies that directly target viral or cellular proteins are limited because of the specificity, drug resistance and rapid clearance from the human body. Therefore, developing safe and potent antiviral agents with activity against viral infection at multiple points in the viral life cycle remains a major challenge. In this report, we propose a new modality to inhibit viral infection by fabricating DNA conjugated gold nanoparticle (DNA-AuNP) networks on cell membranes as a protective barrier. The DNA-AuNPs networks were found, via a plaque formation assay and viral titers, to have potent antiviral ability and protect host cells from human respiratory syncytial virus (RSV). Confocal immunofluorescence image analysis showed 80 ± 3.8% of viral attachment, 91.1 ± 0.9% of viral entry and 87.9 ± 2.8% of viral budding were inhibited by the DNA-AuNP networks, which were further confirmed by real-time fluorescence imaging of the RSV infection process. The antiviral activity of the networks may be attributed to steric effects, the disruption of membrane glycoproteins and limited fusion of cell membrane bilayers, all of which play important roles in viral infection. Therefore, our results suggest that the DNA-AuNP networks have not only prophylactic effects to inhibit virus attachment and entry, but also therapeutic effects to inhibit viral budding and cell-to-cell spread. More importantly, this proof-of-principle study provides a pathway for the development of a universal, broad-spectrum antiviral therapy.
authors.affiliation: Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, PR China.
authors.forename: Chun Mei
authors.initials: CM
authors.lastname: Li
authors.affiliation: Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, PR China.
authors.forename: Lin Ling
authors.initials: LL
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, PR China.
authors.forename: Xiao Xi
authors.initials: XX
authors.lastname: Yang
authors.affiliation: Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, PR China.
authors.forename: Xiao Yan
authors.initials: XY
authors.lastname: Wan
authors.affiliation: Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, PR China.
authors.forename: Wen Bi
authors.initials: WB
authors.lastname: Wu
authors.affiliation: Chongqing Key Laboratory of Biomedical Analysis (Southwest University), Chongqing Science & Technology Commission, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China.
authors.forename: Shu Jun
authors.initials: SJ
authors.lastname: Zhen
authors.affiliation: Chongqing Key Laboratory of Biomedical Analysis (Southwest University), Chongqing Science & Technology Commission, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China.
authors.forename: Yuan Fang
authors.initials: YF
authors.lastname: Li
authors.affiliation: College of Life Sciences, Southwest University, Chongqing 400715, PR China.
authors.forename: Ling Fei
authors.initials: LF
authors.lastname: Luo
authors.affiliation: Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, PR China; Chongqing Key Laboratory of Biomedical Analysis (Southwest University), Chongqing Science & Technology Commission, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China. Electronic address: chengzhi@swu.edu.cn.
authors.forename: Cheng Zhi
authors.initials: CZ
authors.lastname: Huang
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000821:virology*; D002470:Cell Survival; D003588:Cytopathogenic Effect, Viral; D004247:DNA / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000821:virology; D017979:Gold Colloid / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000473:pathology; D058726:Nanoconjugates / Q000008:administration & dosage*; D053758:Nanoparticles / Q000008:administration & dosage*; D012136:Respiratory Syncytial Viruses / Q000187:drug effects* / Q000502:physiology; D010948:Viral Plaque Assay; D053585:Virus Attachment / Q000187:drug effects*; D053586:Virus Internalization / Q000187:drug effects*; D057074:Virus Release / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D017979:Gold Colloid; D058726:Nanoconjugates; D004247:DNA
keywords: Cell membrane; DNA-AuNP networks; Inhibition; Viral infection