@article{MRA, author = {Michelle Miller and Alben Sigamani and David Platt and Kevin Mayo}, title = { Carbohydrate PL-M binds galectin-3 to inhibit SARS-CoV-2 viral entry into cells}, journal = {Medical Research Archives}, volume = {12}, number = {8}, year = {2024}, keywords = {}, abstract = {Galectin-3 (Gal-3) binds to glycans on the spike protein S1 domain of the SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) virus, thereby facilitating viral entry into cells. Because little is known about how to antagonize Gal-3 to block viral activity, we developed a pectin-derived polysaccharide of a(1-6)-D-mannopyranose (termed “ProLectin M” or PL-M) and studied its effect on Vero cells being infected with SARS-CoV-2 virus. Using this novel glycovirology approach, we demonstrated a significant reduction in viral load with no demonstrable cytotoxicity. We also evaluated the efficacy of PL-M in a randomized, double-blinded, placebo-controlled clinical study in 34 patients with mild to moderately severe COVID-19. Overall, treatment with PL-M significantly (p = 0.001) increased RT-PCR cycle counts for N and ORF genes on days 3 (Ct values 32.09 ± 2.39 and 30.69 ± 3.38, respectively) and 7 (Ct values 34.91 ± 0.39 and 34.85 ± 0.61, respectively) compared to placebo. From day 3 post-treatment, all subjects were RT-PCR negative for both genes in the PL-M treatment group, whereas placebo subjects remained positive. On the molecular level, our NMR studies show that PL-M binds relatively strongly to Gal-3, supporting the idea of an antagonist effect on the lectin. Gal-3 also binds strongly to sugar binding sites on the SARS-CoV2 virus spike protein S1 domain as evidenced by competitive lactose binding. In this regard, PL-M competes with the spike protein for binding to Gal-3 and thereby compromises viral entry into susceptible target cells, thus helping to explain our positive clinical effect from PL-M on the course of viral infection. This report provides a brief review of what is already known about PL-M and its effects on SARS-CoV2 virus, as well as new results on an expanded clinical trial with PL-M and NMR studies on the molecular mechanism of action of PL-M, Gal-3, and the SARS-CoV2 viral spike protein S1 from the Omicron variant.}, issn = {2375-1924}, doi = {10.18103/mra.v12i8.5616}, url = {https://esmed.org/MRA/mra/article/view/5616} }