Carbohydrate prolectin-M, a galectin-3 antagonist, blocks SARS-CoV-2 activity

https://doi.org/10.53730/ijhs.v6nS4.10033

Authors

  • Alben Sigamani Research Consultancy, Senior Consultant, Clinical Research, Bangalore, India
  • Hana Chen-Walden Medical officer, Bioxytran
  • Jayeeta Pahan Murli Krishna Pharma Pvt. Ltd., Deputy General Manager, Ranjangaon, Maharashtra, India
  • Michelle C. Miller Department of Biochemistry, Molecular Biology & Biophysics, University of Minnesota, 6-155 Jackson Hall, Minneapolis, MN 55101 USA
  • Kevin H. Mayo Department of Biochemistry, Molecular Biology & Biophysics, University of Minnesota, 6-155 Jackson Hall, Minneapolis, MN 55101 USA
  • David Platt Chief Chemist, Bioxytran,

Keywords:

carbohydrate prolactin, blocks SARS-CoV-2 activity, COVID-19 disease

Abstract

The SARS-COV-2 (severe acute respiratory syndrome coronavirus 2) virus binds to human lectins to gain entry into cells to replicate. Blocking the virus’s entry using a complex polysaccharide component of [a (1-6)- D-mannopyranose termed “ProLectin M” has an effect on viral replication as a therapeutic tool and a safe alternative to existing antiviral therapies. Little is known about how galectin-3 inhibits viral entry into cells and its impact on the course of viral infection. Here, we investigated the effect of these non-cytotoxic polysaccharides on Vero cells infected with SARS-CoV-2 and demonstrated a dose-dependent reduction in viral load over a 48-hour viral incubation period. A pilot clinical study in five patients with laboratory-confirmed COVID-19 disease was treated with an oral formulation of ProLectin M, and all patients achieved complete disease remission with zero hospitalization or need for oxygen support. Moreover, the viral load was significantly lowered within 2 days of drug administration. On the viral envelope, glycans often play a crucial role in enabling pathogen transmission and/or entry into susceptible target cells. On the molecular level, our NMR spectroscopic studies show that ProLectin M binds relatively strongly to galectin-3, supporting the idea of an antagonist effect on the lectin. 

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References

References

Cui, J., Li, F. & Shi, Z.-L. Origin and evolution of pathogenic coronaviruses. Nature Reviews Microbiology 17, 181-192 (2019).

Mousavizadeh, L. & Ghasemi, S. Genotype and phenotype of COVID-19: Their roles in pathogenesis. J Microbiol Immunol Infect 54, 159-163, doi:10.1016/j.jmii.2020.03.022 (2021).

Khandia, R. et al. Emergence of SARS-CoV-2 Omicron (B.1.1.529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic. Environ Res 209, 112816, doi:10.1016/j.envres.2022.112816 (2022).

Gong, Y., Qin, S., Dai, L. & Tian, Z. The glycosylation in SARS-CoV-2 and its receptor ACE2. Signal Transduction and Targeted Therapy 6, 396, doi:10.1038/s41392-021-00809-8 (2021).

Casalino, L. ACS Cent. Sci. 6, doi:10.1021/acscentsci.0c01056 (2020).

Gobeil, S. M. C. Science, doi:10.1126/science.abi6226 (2021).

Díaz-Alvarez, L. & Ortega, E. The Many Roles of Galectin-3, a Multifaceted Molecule, in Innate Immune Responses against Pathogens. Mediators Inflamm 2017, 9247574, doi:10.1155/2017/9247574 (2017).

Sato, S., St-Pierre, C., Bhaumik, P. & Nieminen, J. Galectins in innate immunity: dual functions of host soluble beta-galactoside-binding lectins as damage-associated molecular patterns (DAMPs) and as receptors for pathogen-associated molecular patterns (PAMPs). Immunol Rev 230, 172-187, doi:10.1111/j.1600-065X.2009.00790.x (2009).

Zhang, C., Wu, Z., Li, J. W., Zhao, H. & Wang, G. Q. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents 55, 105954, doi:10.1016/j.ijantimicag.2020.105954 (2020).

England, J. T. et al. Weathering the COVID-19 storm: Lessons from hematologic cytokine syndromes. Blood Rev 45, 100707, doi:10.1016/j.blre.2020.100707 (2021).

Wang, J., Jiang, M., Chen, X. & Montaner, L. J. Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts. J Leukoc Biol 108, 17-41, doi:10.1002/jlb.3covr0520-272r (2020).

Okamoto, M., Hidaka, A., Toyama, M. & Baba, M. Galectin-3 is involved in HIV-1 expression through NF-κB activation and associated with Tat in latently infected cells. Virus Res 260, 86-93, doi:10.1016/j.virusres.2018.11.012 (2019).

Zhou, W. et al. Galectin-3 activates TLR4/NF-κB signaling to promote lung adenocarcinoma cell proliferation through activating lncRNA-NEAT1 expression. BMC Cancer 18, 580, doi:10.1186/s12885-018-4461-z (2018).

De Biasi, S. et al. Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia. Nat Commun 11, 3434, doi:10.1038/s41467-020-17292-4 (2020).

Kalfaoglu, B., Almeida-Santos, J., Tye, C. A., Satou, Y. & Ono, M. T-Cell Hyperactivation and Paralysis in Severe COVID-19 Infection Revealed by Single-Cell Analysis. Front Immunol 11, 589380, doi:10.3389/fimmu.2020.589380 (2020).

Liu, X. et al. Single-Cell Analysis Reveals Macrophage-Driven T Cell Dysfunction in Severe COVID-19 Patients. medRxiv, 2020.2005.2023.20100024, doi:10.1101/2020.05.23.20100024 (2020).

Tortorici, M. A. et al. Structural basis for human coronavirus attachment to sialic acid receptors. Nat Struct Mol Biol 26, 481-489, doi:10.1038/s41594-019-0233-y (2019).

Behloul, N., Baha, S., Shi, R. & Meng, J. Role of the GTNGTKR motif in the N-terminal receptor-binding domain of the SARS-CoV-2 spike protein. Virus Res 286, 198058, doi:10.1016/j.virusres.2020.198058 (2020).

Milanetti, E. et al. In-Silico Evidence for a Two Receptor Based Strategy of SARS-CoV-2. Front Mol Biosci 8, 690655, doi:10.3389/fmolb.2021.690655 (2021).

Caniglia, J. L., Asuthkar, S., Tsung, A. J., Guda, M. R. & Velpula, K. K. Immunopathology of galectin-3: an increasingly promising target in COVID-19. F1000Res 9, 1078, doi:10.12688/f1000research.25979.2 (2020).

Ippel, H. et al. Intra- and intermolecular interactions of human galectin-3: assessment by full-assignment-based NMR. Glycobiology 26, 888-903, doi:10.1093/glycob/cww021 (2016).

Delaglio, F. et al. NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J Biomol NMR 6, 277-293, doi:10.1007/BF00197809 (1995).

Johnson, B. A. & Blevins, R. A. NMR View: A computer program for the visualization and analysis of NMR data. J Biomol NMR 4, 603-614, doi:10.1007/BF00404272 (1994).

Sigamani, A. et al. Galectin antagonist use in mild cases of SARS-CoV-2; pilot feasibility randomised, open label, controlled trial. medRxiv, 2020.2012.2003.20238840, doi:10.1101/2020.12.03.20238840 (2020).

Williamson, M. P. Using chemical shift perturbation to characterise ligand binding. Prog Nucl Magn Reson Spectrosc 73, 1-16, doi:10.1016/j.pnmrs.2013.02.001 (2013).

Di Lella, S. et al. When galectins recognize glycans: from biochemistry to physiology and back again. Biochemistry 50, 7842-7857, doi:10.1021/bi201121m (2011).

Organization, W. H. COVID-19 vaccine tracker and landscape, 2022).

Harvey, W. T. et al. SARS-CoV-2 variants, spike mutations and immune escape. Nature Reviews Microbiology 19, 409-424, doi:10.1038/s41579-021-00573-0 (2021).

Lam, S. D., Waman, V. P., Orengo, C. & Lees, J. Insertions in the SARS-CoV-2 Spike N-Terminal Domain May Aid COVID-19 Transmission. bioRxiv, 2021.2012.2006.471394, doi:10.1101/2021.12.06.471394 (2021).

Lee, Y.-K. et al. Carbohydrate Ligands for COVID-19 Spike Proteins. Viruses 14, doi:10.3390/v14020330 (2022).

Suryasa, I. W., Rodríguez-Gámez, M., & Koldoris, T. (2021). The COVID-19 pandemic. International Journal of Health Sciences, 5(2), vi-ix. https://doi.org/10.53730/ijhs.v5n2.2937

Suryasa, I. W., Rodríguez-Gámez, M., & Koldoris, T. (2022). Post-pandemic health and its sustainability: Educational situation. International Journal of Health Sciences, 6(1), i-v. https://doi.org/10.53730/ijhs.v6n1.5949

Khidoyatova, M. R., Kayumov, U. K., Inoyatova, F. K., Fozilov, K. G., Khamidullaeva, G. A., & Eshpulatov, A. S. (2022). Clinical status of patients with coronary artery disease post COVID-19. International Journal of Health & Medical Sciences, 5(1), 137-144. https://doi.org/10.21744/ijhms.v5n1.1858

Published

30-06-2022

How to Cite

Sigamani, A., Chen-Walden, H., Pahan, J., Miller, M. C., Mayo, K. H., & Platt, D. (2022). Carbohydrate prolectin-M, a galectin-3 antagonist, blocks SARS-CoV-2 activity. International Journal of Health Sciences, 6(S4), 6671–6683. https://doi.org/10.53730/ijhs.v6nS4.10033

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Section

Peer Review Articles