Alben Sigamani*, Mathu Ruthra, Sudhishma, Samarth Shetty, Madhavi, Anup Chugani, Hana Chen-Walden, David Platt, Thomas Kutty
Importance: Novel SARS-CoV-2 virus has infected nearly 100 million 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 binding site-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/μL determines active viral replication.
Design and intervention: Pilot 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 (galactomannan) 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.
Results: This 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).
在第 1、7 和 14 天在诊所进行的 rRT-PCR 检测中，3 名参与者（60%）在第 7 天转为阴性，所有参与者在第 14 天转为阴性并保持阴性直到第 28 天。在 SoC 组中，2 名参与者在基线时可检测到的病毒载量为零，2 名参与者在第 14 天的检测结果为阴性，最后一名参与者在第 28 天仍然呈阳性。没有严重不良事件，所有参与者在第 28 天之前均无临床症状，且具有反应性免疫球蛋白 G (IgG)。
试验相关性：这项先导研究证明，在 COVID-19 中使用 Galectin 拮抗剂进行试验是可行且安全的。这是一种阻止病毒进入及其随后复制的新机制。