
METHYLENE BLUE INHIBITS THE INTERACTION BETWEEN HEPARAN SULFATE AND SARS-COV-2 SPIKE PROTEIN; A REVIEW OF EVIDENCE FOR A HYPOTHESIS.
Author(s) -
Neluwa-Liyanage R. Indika,
Nirmalie Gayathrie Fonseka
Publication year - 2021
Publication title -
malaysian journal of medical research
Language(s) - English
Resource type - Journals
ISSN - 2550-1607
DOI - 10.31674/mjmr.2021.v05i04.002
Subject(s) - heparan sulfate , methylene blue , chemistry , biophysics , glycosaminoglycan , heparin , sulfation , biochemistry , microbiology and biotechnology , biology , photocatalysis , catalysis
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.