Coronaviruses Vaccines Development Based on Chimeric Proteins

Abstract

The known antiviral vaccines based on ferritin-fused antigens are synthesized in the HEK (Human Embryonic Kidney cells) expression system, making them difficult for large-scale production. In this work, we present the potential vaccine based on Escherichia coli ferritin fused with a receptor-binding domain (RBD) of the spike glycoprotein from SARS-CoV-2 expressed and purified from E. coli cells. This chimeric protein is a potential perspective candidate for creating a platform for rapid development of vaccines against coronaviruses and other pathogens. Expression and purification from E. coli cells together with small-angle X-ray scattering experiments showed multimeric assemblies of these chimeric proteins. Additionally to characterize the nanoparticle we used computer molecular modeling, molecular dynamics simulations and quantum biochemical analysis which provide new information about the interaction driving the complex formation and stabilization as well as the type of interactions that support it. Besides, computational analysis may help in understanding of the best conformations and domains involved in the interactions which may help to engineer the enhanced complex.

Authors 12

1. Valentin Gordeliy corresponding

   Centre National de la Recherche Scientifique · Commissariat à l'Énergie Atomique et aux Énergies Alternatives · CEA Grenoble · Institut de Biologie Structurale · Université Grenoble Alpes

   Affiliation as printed

   Institut de Biologie Structurale (IBS), Université Grenoble Alpes, CEA, CNRS, 38000 Grenoble, France

2. Alexey Vlasov Aachen Institute of Crystallography

   Moscow Institute of Physics and Technology · Joint Institute for Nuclear Research · RWTH Aachen University

   Affiliation as printed

   Institute of Crystallography, RWTH Aachen University, 52066 Aachen, Germany

   Joint Institute for Nuclear Research, 141980 Dubna, Russia

   Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology

3. Anastasiia D. Vlasova

   Moscow Institute of Physics and Technology

   Affiliation as printed

   Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia

4. Sergey V. Bazhenov

   National Research University Higher School of Economics · Moscow Institute of Physics and Technology

   Affiliation as printed

   National Research University Higher School of Economics, 101000, Moscow, Russia

   Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia

5. Yury L. Ryzhykau

   Moscow Institute of Physics and Technology · Joint Institute for Nuclear Research

   Affiliation as printed

   Joint Institute for Nuclear Research, 141980 Dubna, Russia

   Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia

6. Nikolay A. Bondarev

   Moscow Institute of Physics and Technology

   Affiliation as printed

   Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia

7. Stepan D. Osipov

   Moscow Institute of Physics and Technology

   Affiliation as printed

   Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia

8. Vsevolod V. Sudarev

   Moscow Institute of Physics and Technology

   Affiliation as printed

   Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia

9. Jackson L. Amaral

   Universidade Federal do Ceará

   Affiliation as printed

   Department of Biochemistry and Molecular Biology, Federal University of Ceara, Fortaleza 60440-900, Brazil

10. Pedro Filho Noronha Souza

    Universidade Federal do Ceará

    Affiliation as printed

    Department of Biochemistry and Molecular Biology, Federal University of Ceara, Fortaleza 60440-900, Brazil

11. И. В. Манухов

    National Research University Higher School of Economics · Moscow Institute of Physics and Technology

    Affiliation as printed

    National Research University Higher School of Economics, 101000, Moscow, Russia

    Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia

12. Alexander I. Kuklin

    Moscow Institute of Physics and Technology · Joint Institute for Nuclear Research

    Affiliation as printed

    Joint Institute for Nuclear Research, 141980 Dubna, Russia

    Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia