ImportanceNovel 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.BackgroundSpike 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 binding site - human galactose binding lectins, is a potential novel target for early treatment in COVID-19.ObjectivesTo 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 measuresCycle 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/μL determines active viral replication.Design and interventionPilot Feasibility Randomised Controlled Open-Label, parallel arm, study. Oral tablets of Prolectin-M were administered along with the best practice, Standard of Care (SoC) and compared against SoC. Voluntarily, consenting individuals, age >18 years, and able to provide frequent nasopharyngeal and oropharyngeal swabs were randomly allocated by REDCap software.The intervention, Prolectin-M was administered as a multi dose regime of 4 gram 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 daytime, for total of 5 days.ResultsThis pilot trial demonstrated the feasibility to recruit and randomize 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 3 (Mann Whitney U = 0.000, p<0.029).rRT-PCR testing done in the clinic on day 1, 7, and 14 had 3 participants (60%) turn negative by day 7 and all turned negative by day 14 and stayed negative until day 28. In the SoC group 2 participants had zero detectable viral loads at baseline, 2 participants tested negative on day 14, and the last participant tested remained positive on day 28. There were no serious adverse events, and all participants were clinically asymptomatic before day 28 with reactive immunoglobulin G (IgG).Trial relevanceThis pilot study proves that it is feasible and safe to perform a trial using a Galectin antagonist in COVID-19. This is a novel mechanism for blocking viral entry and its subsequent replication.Trial RegistrationClinical Trials.gov identifier NCT04512027; CTRI ref. CTRI/2020/09/027833