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


Alben Sigamani, Kevin H Mayo, Hana Chen-Walden, Surender Reddy, David Platt



SARS-CoV-2 vaccines play an important role in reducing disease severity, hospitalization, and death, although they failed to prevent the transmission of SARS-CoV-2 variants. Therefore, an effective antiviral such as a Galectin-3 (Gal-3) antagonist might have the potential to prevent viral transmission. ProLectin-M (PL-M), a Gal-3 antagonist, has been shown to have anti-SARS-CoV-2 activity in previous studies.


The present study aimed to further evaluate the antiviral effect of PL-M tablets in 34 subjects with COVID-19 disease, in addition to determining the antiviral mechanisms of PL-M by NMR studies.


The efficacy of PL-M was evaluated in a randomized, double-blind, placebo-controlled clinical study in patients with mild to moderately severe COVID-19. Primary endpoints included changes in absolute RT-PCR Ct values of the nucleocapsid and open reading frame (ORF) genes from baseline to days 3 and 7. The incidence of adverse events, changes in blood biochemistry, inflammatory biomarkers, and levels of antibodies against COVID-19 were also evaluated as part of the safety evaluation. In vitro 1H-15N HSQC NMR spectroscopy studies were also performed to determine the interactions of PL-M with Gal-3 and the S1 spike protein of SARS-CoV-2.


PL-M treatment significantly (p = 0.001) increased RT-PCR cycle counts for N and ORF genes on days 3 (Ct values 32.09 and 30.69 +/-3.38, respectively) and 7 (Ct values 34.91 +/-0.39 and 34.85 +/-0.61, respectively) compared to placebo. All subjects were RT-PCR negative for both genes in the PL-M treatment group from day 3 onwards. The Ct values in the placebo group were consistently less than 29 (target cycle count 29) for both genes until day 7, and no placebo subjects were negative by RT-PCR. 1H-15N HSQC NMR spectroscopy revealed that PL-M specifically binds Gal-3 in the same way as the structurally similar NTD of the SARS-CoV-2 S1 subunit.


PL-M is safe and effective for clinical use in reducing viral load and promoting rapid viral clearance in COVID-19 patients by inhibiting SARS-CoV-2 entry into cells through inhibition of Gal-3.