Abstract
The evolution of the SARS-CoV-2 virus during the COVID-19 pandemic was accompanied by the emergence of new heavily mutated viral variants with increased infectivity and/or resistance to detection by the human immune system. To respond to the urgent need for advanced methods and materials to empower a better understanding of the mechanisms of virus’s adaptation to human host cells and to the immuno-resistant human population, we suggested using recombinant filamentous bacteriophages, displaying on their surface foreign peptides termed “mimotopes”, which mimic the structure of viral receptor-binding sites on the viral spike protein and can serve as molecular probes in the evaluation of molecular mechanisms of virus infectivity. In opposition to spike-binding antibodies that are commonly used in studying the interaction of the ACE2 receptor with SARS-CoV-2 variants in vitro, phage spike mimotopes targeted to other cellular receptors would allow discovery of their role in viral infection in vivo using cell culture, tissue, organs, or the whole organism. Phage mimotopes of the SARS-CoV-2 Spike S1 protein have been developed using a combination of phage display and molecular mimicry concepts, termed here “phage mimicry”, supported by bioinformatics methods. The key elements of the phage mimicry concept include: (1) preparation of a collection of p8-type (landscape) phages, which interact with authentic active receptors of live human cells, presumably mimicking the binding interactions of human coronaviruses such as SARS-CoV-2 and its variants; (2) discovery of closely related amino acid clusters with similar 3D structural motifs on the surface of natural ligands (FGF1 and NRP1), of the model receptor of interest FGFR and the S1 spike protein; and (3) an ELISA analysis of the interaction between candidate phage mimotopes with FGFR3 (a potential alternative receptor) in comparison with ACE2 (the authentic receptor).
| Original language | English |
|---|---|
| Article number | 384 |
| Journal | Viruses |
| Volume | 14 |
| Issue number | 2 |
| DOIs | |
| State | Published - 14 Feb 2022 |
Bibliographical note
Publisher Copyright:© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
Funding
Funding: Development of anticancer cell-targeted landscape phages was funded by NIH grants to V.A.P.: 5R01CA125063-01-05, 1R01CA193246-01-05 and NIH (NCI) 1U54CA151881. Project support was provided by the College of Veterinary Medicine (Dean Calvin M. Johnson, DVM, PhD) through the Auburn University Research Initiative in Cancer (AURIC) award to V.A.P. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding organizations.
| Funders | Funder number |
|---|---|
| National Institutes of Health | 1R01CA193246-01-05 |
| National Cancer Institute | R01CA125063, 1U54CA151881 |
| Auburn University | |
| College of Veterinary Medicine, Purdue University |
Keywords
- Alternative receptors
- Landscape phage
- Mimotope
- Molecular mimicry
- Phage display
- SARS-CoV-2 virus
- Spike protein
- Virus receptors
