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

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.

Galectin approach to lower covid transmission - Drug Development for clinical use

“…Additionally, no major adverse effects or abnormalities in vital signs, haematological, or biochemical parameters were identified after 7 days of PL-M administration. Our findings were consistent with those of earlier in vitro and clinical studies [23,24].…”

“…In our previous pilot study on 10 patients with COVID-19 infection, we found that oral administration of PL-M (chewable tablets) increased PCR cycle threshold, indicating the elimination of SARS-CoV-2 as well as a reduction in viral load in patients [23]. Further in vitro studies on SARS-CoV-2-infected Vero cells, followed by NMR analysis, revealed that PL-M strongly binds to human Gal-3, resulting in a reduction in viral load in Vero cells [24]. In this study, we further share the results of a clinical trial on CODID-19 patients and an NMR experiment with the extracted spike proteins.…”

“…As previously mentioned, human Gal-3 is crucial to the entry of SARS-CoV-2, and its blockage may prevent the progression of the disease. In an early in vitro study, we showed that PL-M lowered viral load and increased its clearance from Vero cells by inhibiting the entry of SARS-CoV-2 into Vero cells following PL-M binding to the NTD of the Gal-3 molecule [24]. Furthermore, in a small clinical study of 10 COVID-19 patients, we found that PL-M treatment resulted in a quick reduction in viral load and increased viral clearance without eliciting any serious adverse effects [23].…”

“…Binding of PL-M to Gal-3 using HSQC NMR. Having established the in vitro and in vivo effectiveness of PL-M against SARS-CoV-2 infectivity [23,24], we sought insight on the molecular level. We hypothesized that PL-M functions in situ by binding to and antagonizing Gal-3, which is known to interact with SARS-CoV-2 to promote viral entry into cells [24].…”

“…Having established the in vitro and in vivo effectiveness of PL-M against SARS-CoV-2 infectivity [23,24], we sought insight on the molecular level. We hypothesized that PL-M functions in situ by binding to and antagonizing Gal-3, which is known to interact with SARS-CoV-2 to promote viral entry into cells [24]. To validate this proposal, we used NMR spectroscopy to assess binding interactions between PL-M and Gal-3, as well as between Gal-3 and SARS-CoV-2 S1 spike protein.…”