Scientists from the Institute of Molecular Biology and Celular de Plantas (CSIC-UPV) obtain nanoparticles coated with antibodies against coronavirus from plant 'biofactories'. This method to produce antibodies, developed together with the Institute of Integrative Systems Biology (CSIC-UV), is economical and avoids contamination with human pathogens.

Use plants as 'biofactories' to produce nanoparticles as a drug vehicle. This is what a team from the Institute of Molecular and Cellular Biology of Plants (IBMCP), a mixed center of the Higher Council for Scientific Research (CSIC) and the Universitat Politècnica de València (UPV), in collaboration with the Instituto de Integrative Systems Biology (I2SySBio), from the CSIC and the Universitat de València. Specifically, they have created nanoparticles with small single-chain monoclonal antibodies (nanobodies) that act against the protein that surrounds the SARS-CoV-2 coronavirus. These nanoparticles could be used as a reagent in diagnostic tests and, after evaluation, as a drug to neutralize virus infection. The results are published in the journal Plant Biotechnology Journal.

The research group led by José Antonio Darós at the IBMCP used plants of the species Nicotiana benthamiana to produce nanoparticles coated with small single-chain monoclonal antibodies, also called 'nanobodies'. Antibodies are essential molecules of the immune system, capable of binding to any foreign structure to launch other mechanisms that destroy potentially dangerous elements for the body (viruses, bacteria, tumor cells...). Specifically, the nanobodies obtained in this work act against the S protein of SARS-CoV-2, the 'key' that allows the coronavirus to infect cells.

Obtaining drugs from plants dates back to the dawn of humanity. Now the process is modified, turning the plants into factories to produce compounds of interest. “In the same way that a compound produced naturally by a plant can be extracted, we induce the production of the molecule we want, in this case nanoparticles coated with nanobodies,” explains José Antonio Darós, CSIC research professor at the IBMCP. To do this, they use the ability of viruses to infect plants quickly and systemically, inserting into the virus genome the gene that encodes the antibody they want to produce.

“Instead of producing these nanobodies as individual molecules, in this project we develop the production of nanoparticles, molecular structures whose scale is nanometric, which serve as a support for the presentation of said antibodies,” reveals Darós. The nanoparticle they use is the viral particle itself, whose structural protein is fused to an antibody. “In this way, when these structural proteins self-assemble, we obtain multivalent macromolecules, which have hundreds of repetitions of the antibody in question,” he describes. This increases their capacity for action, since “multivalent nanobodies show a greater avidity towards their target and, therefore, are more powerful in neutralizing it.”

Advantages of using plants as biofactories

This system for producing multivalent nanoparticles in plant biofactories could be used to produce any nanobody of interest, the researchers say. "In particular, the nanoparticles developed in this work could be used as a reagent in coronavirus diagnostic tests, such as the widely marketed test strips. In a subsequent step, their ability to also be used as therapeutic agents capable of inhibiting viral spread could be evaluated," comments Fernando Merwaiss, postdoctoral researcher at the IBMCP and co-principal investigator of the study.

Regarding the advantages of using plants as biofactories to generate compounds of interest pharmacological, in addition to the low production cost (plants only need sunlight, water, carbon dioxide and some inorganic nutrients to grow), “it has other advantages such as the unlikelihood of contamination with human pathogens, the ease of scaling production and the ability to carry out post-translational modifications similar to those of mammalian cells,” Merwaiss highlights. Furthermore, the method developed by the IBMCP and I2SysBio team adds the possibility of producing hundreds of nanobodies grouped in the same multivalent macromolecule, which significantly increases their capacity for action.

Reference:

Merwaiss, F., Lozano-Sanchez, E., Zulaica, J., Rusu, L., Vazquez-Vilar, M., Orzáez, D., Rodrigo, G., Geller, R. and Daròs, J.-A. (2023), Plant virus-derived nanoparticles decorated with genetically encoded SARS-CoV-2 nanobodies display enhanced neutralizing activity. Plant Biotechnol. J. DOI: https://doi.org/10.1111/pbi.14230

Source: CSIC