Sigamani Alben, Mayo Kevin H, Miller Michelle C, Chen-Walden Hana, Reddy Surendar, Platt David
Carmel Research Consultancy Pvt. Ltd., Bengaluru 560025, Karnataka, India.
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, 6-155 Jackson Hall, 321 Church Street, Minneapolis, MN 55455, USA.
Vaccines (Basel). 2023 Mar 25;11(4):731. doi: 10.3390/vaccines11040731.
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 the transmission of COVID-19. ProLectin-M (PL-M), a Gal-3 antagonist, was shown to interact with Gal-3 and thereby prevent cellular entry of SARS-CoV-2 in previous studies.
The present study aimed to further evaluate the therapeutic effect of PL-M tablets in 34 subjects with COVID-19.
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 the 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.
PL-M treatment significantly (p = 0.001) increased RT-PCR cycle counts for N and ORF genes on days 3 (Ct values 32.09 ± 2.39 and 30.69 ± 3.38, respectively) and 7 (Ct values 34.91 ± 0.39 and 34.85 ± 0.61, respectively) compared to a placebo treatment. On day 3, 14 subjects in the PL-M group had cycle counts for the N gene above the cut-off value of 29 (target cycle count 29), whereas on day 7, all subjects had cycle counts above the cut-off value. Ct values in placebo subjects were consistently less than 29, and no placebo subjects were RT-PCR-negative until day 7. Most of the symptoms disappeared completely after receiving PL-M treatment for 7 days in more patients compared to the placebo group.
PL-M is safe and effective for clinical use in reducing viral loads and promoting rapid viral clearance in COVID-19 patients by inhibiting SARS-CoV-2 entry into cells through the inhibition of Gal-3.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）疫苗在降低疾病严重程度、住院率和死亡率方面发挥着重要作用，尽管它们未能预防SARS-CoV-2变体的传播。因此，一种有效的半乳糖凝集素-3（Gal-3）抑制剂可用于治疗和预防2019冠状病毒病（COVID-19）的传播。在先前的研究中，半乳糖凝集素-3拮抗剂ProLectin-M（PL-M）被证明可与Gal-3相互作用，从而阻止SARS-CoV-2进入细胞。
本研究旨在进一步评估PL-M片对34例COVID-19患者的治疗效果。
在一项针对轻至中度严重COVID-19患者的随机、双盲、安慰剂对照临床研究中评估PL-M的疗效。主要终点包括从基线到第3天和第7天核衣壳和开放阅读框（ORF）基因的绝对逆转录聚合酶链反应（RT-PCR）Ct值的变化。作为安全性评估的一部分，还评估了不良事件的发生率、血液生化指标的变化、炎症生物标志物以及抗COVID-19抗体水平。
与安慰剂治疗相比，PL-M治疗在第3天（N基因和ORF基因的Ct值分别为32.09±2.39和30.69±3.38）和第7天（N基因和ORF基因的Ct值分别为34.91±0.39和34.85±0.61）显著（p = 0.001）增加了N基因和ORF基因的RT-PCR循环数。在第3天，PL-M组中有14名受试者的N基因循环数高于临界值29（目标循环数29），而在第7天，所有受试者的循环数均高于临界值。安慰剂组受试者的Ct值始终低于29，直到第7天没有安慰剂组受试者的RT-PCR检测呈阴性。与安慰剂组相比，更多患者在接受PL-M治疗7天后大多数症状完全消失。
PL-M通过抑制Gal-3来抑制SARS-CoV-2进入细胞，从而在降低COVID-19患者的病毒载量和促进病毒快速清除方面临床使用安全有效。
