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Site-selective proteolytic cleavage of plant viruses by photoactive chiral nanoparticles

Nature Catalysis volume 5, pages 694–707 (2022)Cite this article

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Abstract

Viral diseases of plants are associated with large health and economic costs. Antiviral agents developed for mammalian organisms have had limited success for plants, necessitating alternative strategies to address this biological and sustainability problem. Here we show that chiral 3 nm Cu1.96S nanoparticles can site-selectively cleave capsid in tobacco mosaic virus under sunlight. With d-penicillamine as surface ligands, the nanoparticles display high affinity to the Gln 99 to Ala 105 segment in the capsid via a network of supramolecular bonds and 3,000–10,000 times lower affinity to capsids of other viruses. Illumination with green light leads to polarization-dependent, protease-like hydrolysis of the amide bond between Asn 101 and Pro 102. Nanoparticles inhibited viral infectivity by 98.7% in protoplasts and 92.6% in plants while avoiding hypersensitive response and large environmental impact. These findings show that nanoparticles combining proteolytic activity due to metal ions and site selectivity due to nanoscale chirality can be used as effective antiviral agents.

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Fig. 1: Synthesis of Pen-modified chiral nanoparticles.
Fig. 2: Circularly polarized light-response interaction between chiral nanoparticles and virus.
Fig. 3: Cleavage site analysis.
Fig. 4: Mechanism of the selective photocleavage of CP by chiral NPs.
Fig. 5: Photocleavage of virus by d-NPs in protoplasts and plants.

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Data availability

The data that support the findings of this study are available from the corresponding authors upon reasonable request. The simulation data of the optimized models of Fig. 4 and the raw data of Table 2 are provided at https://doi.org/10.6084/m9.figshare.20045621. Source data are provided with this paper.

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Acknowledgements

This work is financially supported by the National Key R&D Program (2021YFA1200300), and is also supported by the National Natural Science Foundation of China (32071400, 21925402, 21977038). N.A.K is grateful to NSF 1463474 and NSF 1566460 for support. We are grateful to the Brazilian funding agencies CAPES (Finance Code 001), CNPq (process 311353/2019-3) and FAPESP (processes 2012/15147-4 and 2013/07296-2) for financial support and the HPC resources provided by the SDumont supercomputer at the National Laboratory for Scientific Computing (LNCC/MCTI, Brazil, http://sdumont.lncc.br) and by the Cloud@UFSCar.

Author information

Author notes

  1. These authors contributed equally: Rui Gao, Liguang Xu, Maozhong Sun, Manlin Xu.

Authors and Affiliations

  1. State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China

    Rui Gao, Liguang Xu, Maozhong Sun, Changlong Hao, Xiao Guo, Chuanlai Xu & Hua Kuang

  2. International Joint Research Laboratory for Biointerface and Biodetection, Jiangnan University, Wuxi, China

    Rui Gao, Liguang Xu, Maozhong Sun, Changlong Hao, Xiao Guo, Chuanlai Xu & Hua Kuang

  3. The Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi, China

    Liguang Xu

  4. Shandong Peanut Research Institute, Qingdao, China

    Manlin Xu

  5. Brazilian Biorenewables National Laboratory (LNBR), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Brazil

    Felippe Mariano Colombari

  6. Department of Chemistry, University of Illinois at Chicago, Chicago, IL, USA

    Xin Zheng & Petr Král

  7. Department of Chemistry, Federal University of São Carlos, São Carlos, Brazil

    André F. de Moura

  8. Tobacco Research Institute of Chinese Academy of Agricultural Sciences, Qingdao, China

    Jinguang Yang

  9. Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA

    Nicholas A. Kotov

  10. Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA

    Nicholas A. Kotov

  11. Michigan Institute for Translational Nanotechnology, Ypsilanti, MI, USA

    Nicholas A. Kotov

  12. Science Center for Future Foods, Jiangnan University, Wuxi, China

    Hua Kuang

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  1. Rui Gao
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Contributions

H.K., N.A.K. and C.X. conceived the project and designed the experiments. J.Y. was responsible for the antiviral experiments on tobacco and plant cells. R.G. was responsible for the synthesis and characterization of the chiral NPs and studied their photoinduced cleavage properties. R.G., L.X. and M.S. carried out the CD, western blot, XPS, X-ray diffraction, LC–MS–MS and ROS experiments. M.X. performed the test on antiviral activity in TMV plants. C.H. and X.G. helped to synthesis, characterize and analyse the mechanism. F.M.C., X.Z., P.K. and A.F.M. performed the MD, QM and DFT simulations, and analysed the results. H.K. and N.A.K. conceptualized the work. C.X. supervised the study. H.K., N.A.K. and C.X. analysed and discussed the results and wrote the manuscript

Corresponding authors

Correspondence to Chuanlai Xu, Jinguang Yang, Nicholas A. Kotov or Hua Kuang.

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Nature Catalysis thanks Fabienne Schwab, Lixia Zhao, Vladimir Lobaskin and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary methods, Figs. 1–42, Tables 1–6, notes 1–14 and references.

Reporting Summary

Supplementary Video 1

Isosurfaces for average electrostatic polarizations of D-NPs and L-NPs interacting with multiple QANPTTA segments of CP monomer in TMV capsid being illuminated with the light in the spectral window from 300 to 1000 nm.

Supplementary Video 2

Polarization maps according to the change in the electronic population for Ala100-Asn101-Pro102-Thr103 fragment (ANPT) interacting with D-NP, upon excitation at 533-534 nm.

Supplementary Video 3

Polarization maps according to the change in the electronic population for Ala100-Asn101-Pro102-Thr103 fragment (ANPT) interacting with L-NP, upon excitation at 533-534 nm.

Source data

Source Data Fig. 5

Statistical Source Data

Source Data Table 1

Statistical Source Data

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Gao, R., Xu, L., Sun, M. et al. Site-selective proteolytic cleavage of plant viruses by photoactive chiral nanoparticles. Nat Catal 5, 694–707 (2022). https://doi.org/10.1038/s41929-022-00823-1

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