Carbohydrate ProLectin-M, a Galectin-3 Antagonist, Blocks SARS-CoV-2 Activity

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 pectin [α (1–6)- D -mannopyranose termed “ProLectin M” and Rhamnogalacturonan-II (RG-II)] that has an effect on viral replication as a therapeutic tool and a safe alternative to existing anti-viral therapies. Little is known about antagonizing galectin-3 viral-blocking activity by inhibiting viral entry into cells and subsequent viral replication, and its impact on the course of infection. Here, we investigated the effect of these non-cytotoxic polysaccharides on Vero cells infected with SARS-CoV-2 virus and demonstrated a dose-dependent reduction in viral load over a 48-hour incubation period with the virus. A pilot clinical study in five patients with laboratory-confirmed COVID-19 disease were treated with an oral formulation of α(1–6)- D -mannopyranose (ProLectin M). All patients achieved complete disease remission with zero hospitalisation or need for oxygen support. Moreover, viral load was significantly lowered within 2 days of drug administration. On the viral envelope, glycans often play a crucial role in enabling transmission of the pathogen and/or entry into its susceptible target cells. In this regard, our NMR spectroscopic studies showed on the molecular level that ProLectin M binds relatively strongly to galectin-3, supporting the idea of an antagonist effect on the lectin. Overall, our study demonstrates that blocking the viral envelope glycans can compromise entry of the virus into susceptible target cells that may translate into a positive clinical effect on the course of infection.