METHYLENE BLUE INHIBITS THE INTERACTION BETWEEN HEPARAN SULFATE AND SARS-COV-2 SPIKE PROTEIN; A REVIEW OF EVIDENCE FOR A HYPOTHESIS.

Authors

  • Neluwa-Liyanage Ruwan Indika Department of Biochemistry, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka.
  • Nirmalie Gayathrie Fonseka National Blood Centre, Colombo 05, Sri Lanka

DOI:

https://doi.org/10.31674/mjmr.2021.v05i04.002

Abstract

The addition of methylene blue to the standard treatment protocol has been shown to improve respiratory rate and oxygen saturation in COVID-19 patients, reducing morbidity and mortality. Evidence to date suggests that methylene blue inhibits protein-protein interactions between SARS-CoV-2 Spike protein and angiotensin-converting enzyme 2, which in turn inhibits the cell entry of SARS-CoV-2. However, the methylene blue dye-binding characteristics of sulfated glycosaminoglycans suggest additional inhibitory effects of the spike protein-heparan sulfate interaction. We hypothesize that the binding of cationic methylene blue neutralizes polyanionic heparan sulfate molecules on the host cell surface. As a consequence, electrostatic interactions between negatively charged heparan sulfate and the positively charged receptor binding domain of SARS-CoV-2 spike protein will be inhibited. Thus, methylene blue will exhibit a "shielding effect" on the heparan sulfate proteoglycans, inhibiting viral attachment to the cell surface. The proposed mechanism corroborates the possible broad-spectrum antiviral activity of methylene blue against multiple human coronaviruses that exploit the electrostatic interactions with sulfated glycosaminoglycans for virus entry. Methylene blue would exhibit the same anti-adhesive activity at the blood-brain-barrier and olfactory neuroepithelium, corroborating potential benefits in ameliorating post-COVID-19 neurological impairment. However, as cationic dyes can bind to both free glycosaminoglycans in circulation as well as proteoglycans attached to the cell surface, co-administration of intravenous heparin could possibly antagonize the proposed antiviral activity. This critical review focuses on empirical evidence to support the hypothesized heparan sulfate-dependent antiviral activity of MB.

Keywords:

Methylene blue, SARS-CoV-2, COVID-19, Heparan sulfate, Proteoglycans, Antiviral

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Published

2021-10-01

How to Cite

Neluwa-Liyanage Ruwan Indika, & Nirmalie Gayathrie Fonseka. (2021). METHYLENE BLUE INHIBITS THE INTERACTION BETWEEN HEPARAN SULFATE AND SARS-COV-2 SPIKE PROTEIN; A REVIEW OF EVIDENCE FOR A HYPOTHESIS. Malaysian Journal of Medical Research (MJMR), 5(4), 4-11. https://doi.org/10.31674/mjmr.2021.v05i04.002