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

Background 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 inhibitor of galectin-3 (Gal-3) could be used to treat and prevent transmission of COVID-19. ProLectin-M (PL-M), a Gal-3 antagonist, has been shown to interact with Gal-3 and thus prevent cellular entry of SARS-CoV-2 in previous studies. Aim The present study aimed to further evaluate the therapeutic effect of PL-M tablets in 34 subjects with COVID-19 disease, in addition to determining the mechanism of PL-M in preventing SARS-CoV-2 cell entry by NMR studies. Methods 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. Results 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. On day 3, 14 subjects in the PL-M group had cycle counts for the N gene above the cut-off of 29 (target cycle count 29), while on day 7 all subjects had cycle counts above the cut-off. Ct values in placebo subjects were consistently less than 29, and no placebo subjects were RT-PCR negative, until day 7. 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. Conclusion 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. ### Competing Interest Statement All the authors have received funding from Pharmalectin, a unit of Bioxytran Inc. Pharmalectin has copyrights to the molecule and Murlikrishna Pharmaceuticals have taken a contract to manufacture the product. The corresponding author receives a consultation fee from Pharmalectin. ### Clinical Trial CTRI/2022/03/040757 ### Funding Statement This study was funded by Pharmalectin, a unit of Bioxytran Inc. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Ethics Committee (IEC) of ESIS Medical College and Hospital, Sanath Nagar, Hyderabad, India (ESIC Registration No: ECR/1303/Inst/TG/2019; Protocol ID: SRSD2001/01/01 and approval date: 01 Feb 2022). As per regulatory standards, the study was registered with the Clinical Trials Registry-India (CTRI/2022/03/040757) on March 3, 2022. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data supporting this study are provided in the main article, supplementary information files, and upon request to the corresponding author.