Galectin antagonist use in mild cases of SARS-CoV-2 cases; pilot feasibility randomised, open label, controlled trial

SIGAMANI, A.; KADAMBI, M.; RUTHRA, M.; SHIVAPRASAD, S.; CHUGANI, A.; CHEN-WALDEN, H.; ALUMPARAMBILL, T.; PLATT, D.

Importance Novel SARS-CoV-2 virus has infected nearly half a billion people across the world and is highly contagious. There is a need for a novel mechanism to block viral entry and stop its replication. Background Spike protein N terminal domain (NTD) of the novel SARS-CoV-2 is essential for viral entry and replication in human cell. Thus the S1 NTD of human coronavirus family, which is similar to a galectin human galactose binding lectins, is a potential novel target for early treatment in COVID-19. Objectives To study the feasibility of performing a definitive trial of using galectin antagonist Prolectin-M as treatment for mild, symptomatic, rRT-PCR positive, COVID-19. Main outcomes and measures Cycle threshold (Ct) value is number of cycles needed to express fluorescence, on real time reverse transcriptase polymerase chain reaction. Ct values expressed for RNA polymerase (Rd/RP) gene +Nucleocapsid gene and the small envelope (E) genes determine infectivity of the individual. A digital droplet PCR based estimation of the Nucleocapid genes (N1+N2) in absolute copies/L determines viral replication. Design and intervention Pilot Feasibility Randomised Controlled Open-Label, parallel arm, study. Oral tablets of Prolectin-M given was administered along with best practice standard of care (SoC) and compared against only SoC. Voluntarily, consenting individuals, aged >18 years, and able to provide frequent nasopharyngeal and oropharyngeal swabs were randomly allocated on REDCap The intervention, Prolectin-M was administered as a multi dose regime of 4gm tablets. Each tablet contained 2 grams of (1-6)-Alpha-D-mannopyranosil mixed with 2 grams of dietary fibre. Each participant took a single chewable tablet every hour, to a maximum of 10 hours in a day. Tablets were administered only during the day, for total of 5 days. Results This pilot trial demonstrated feasibility to recruit and randomize 10 participants. By day 7, following treatment with Prolectin-M, Ct value of Rd/Rp + N gene increased by16.41 points, 95% (CI 0.3527 to 32.48, p=0.047). Similarly, small envelope (E) gene also increased by 17.75 points (95% CI;-0.1321 to 35.63, p = 0.05). The expression of N1, N2 genes went below detectable thresholds by day 7, (Mann whitney U = 0.000, p<0.029). Three participants (60%) turned rRT-PCR negative by day 7, compared to none in the SoC alone group. There were no serious adverse events, and all participants were clinically asymptomatic before day 28 with reactive immunoglobulin G (IgG). Among the SoC alone arm, two participants had zero detectable viral loads even at baseline. Trial relevance This pilot study proves that it is feasible and safe to perform a trial, using Prolectin-M, as Galectin antagonist in COVID-19. A novel mechanism for blocking viral entry and its subsequent replication is reported here. Trial Registration Clinical Trials.gov identifier NCT04512027; CTRI ref. CTRI/2020/09/027833.