Galectin Antagonist use in Mild Cases of SARS-CoV-2: Pilot Feasibility Randomised, Open Label, Controlled Trial

Importance: Novel SARS-CoV-2 virus has infected nearly 100 million people across the world and is highly\r\ncontagious. There is a need for a novel mechanism to block viral entry and stop its replication.\r\nBackground: Spike protein N Terminal Domain (NTD) of the novel SARS-CoV-2 is essential for viral entry and\r\nreplication in human cell. Thus the S1 NTD of human coronavirus family, which is similar to a galectin binding\r\nsite-human galactose binding lectins, is a potential novel target for early treatment in COVID-19.\r\nObjectives: To study the feasibility of performing a definitive trial of using galectin antagonist–Prolectin-M as\r\ntreatment for mild, symptomatic, rRT-PCR positive, COVID-19.\r\nMain outcomes and measures: Cycle threshold (Ct) value is number of cycles needed to express fluorescence,\r\non real time reverse transcriptase polymerase chain reaction. Ct values expressed for RNA polymerase (Rd/RP)\r\ngene+Nucleocapsid gene and the small envelope (E) genes determine infectivity of the individual. A digital droplet\r\nPCR based estimation of the Nucleocapid genes (N1+N2) in absolute copies/μL determines active viral replication.\r\nDesign and intervention: Pilot Feasibility Randomised Controlled Open-Label, parallel arm, study. Oral tablets of\r\nProlectin-M were administered along with the best practice, Standard of Care (SoC) and compared against SoC.\r\nVoluntarily, consenting individuals, age\u003e18 years, and able to provide frequent nasopharyngeal and oropharyngeal\r\nswabs were randomly allocated by REDCap software.\r\nThe intervention, Prolectin-M was administered as a multi dose regime of 4 gram tablets. Each tablet contained 2\r\ngrams of (1-6)-Alpha-D-mannopyranosil (galactomannan) mixed with 2 grams of dietary fibre. Each participant took\r\na single chewable tablet every hour, to a maximum of 10 hours in a day. Tablets were administered only during the\r\ndaytime, for total of 5 days.\r\nResults: This pilot trial demonstrated the feasibility to recruit and randomize participants. By day 7, following\r\ntreatment with Prolectin-M, Ct value of Rd/Rp+N gene increased by16.41 points, 95% (CI 0.3527 to 32.48,\r\np=0.047). Similarly, small envelope (E) gene also increased by 17.75 points (95% CI,-0.1321 to 35.63, p=0.05). The\r\nexpression of N1, N2 genes went below detectable thresholds by day 3 (Mann Whitney U=0.000, p\u003c0.029).\r\nrRT-PCR testing done in the clinic on day 1, 7, and 14 had 3 participants (60%) turn negative by day 7 and all\r\nturned negative by day 14 and stayed negative until day 28. In the SoC group 2 participants had zero detectable\r\nviral loads at baseline, 2 participants tested negative on day 14, and the last participant remained positive on day 28.\r\nThere were no serious adverse events, and all participants were clinically asymptomatic before day 28 with reactive\r\nimmunoglobulin G (IgG).\r\nTrial relevance: This pilot study proves that it is feasible and safe to perform a trial using a Galectin antagonist in\r\nCOVID-19. This is a novel mechanism for blocking viral entry and its subsequent replication.