Repurposing Astragalus Polysaccharide PG2 for Inhibiting ACE2 and SARS-CoV-2 Spike Syncytial Formation and Anti-Inflammatory Effects

Abstract

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global public health. In an effort to develop novel anti-coronavirus therapeutics and achieve prophylactics, we used gene set enrichment analysis (GSEA) for drug screening and identified that Astragalus polysaccharide (PG2), a mixture of polysaccharides purified from Astragalus membranaceus, could effectively reverse COVID-19 signature genes. Further biological assays revealed that PG2 could prevent the fusion of BHK21-expressing wild-type (WT) viral spike (S) protein and Calu-3-expressing ACE2. Additionally, it specifically prevents the binding of recombinant viral S of WT, alpha, and beta strains to ACE2 receptor in our non-cell-based system. In addition, PG2 enhances let-7a, miR-146a, and miR-148b expression levels in the lung epithelial cells. These findings speculate that PG2 has the potential to reduce viral replication in lung and cytokine storm via these PG2-induced miRNAs. Furthermore, macrophage activation is one of the primary issues leading to the complicated condition of COVID-19 patients, and our results revealed that PG2 could regulate the activation of macrophages by promoting the polarization of THP-1-derived macrophages into an anti-inflammatory phenotype. In this study, PG2 stimulated M2 macrophage activation and increased the expression levels of anti-inflammatory cytokines IL-10 and IL-1RN. Additionally, PG2 was recently used to treat patients with severe COVID-19 symptoms by reducing the neutrophil-to-lymphocyte ratio (NLR). Therefore, our data suggest that PG2, a repurposed drug, possesses the potential to prevent WT SARS-CoV-2 S-mediated syncytia formation with the host cells; it also inhibits the binding of S proteins of WT, alpha, and beta strains to the recombinant ACE2 and halts severe COVID-19 development by regulating the polarization of macrophages to M2 cells.

Complementary and alternative medicine: A narrative review of nutritional approaches for cancer-related fatigue

“…The injection of PG2, suggested to possess properties that are anti-inflammatory, immune-regulating, and beneficial for hematopoiesis, has been reported to have a notable positive impact on both fatigue and quality of life. [ 51 , 52 ] It has been shown that PG2 helps to improve the neutrophil-to-lymphocyte ratio in lung cancer patients treated with immunotherapy. [ 53 ] All 3 RCTs examined patients with advanced cancer.…”

The Mechanisms of Polysaccharides from Tonic Chinese Herbal Medicine on the Enhancement Immune Function: A Review

“…However, no research has discovered that the tonic Chinese herbal medicine polysaccharides can result in a cytokine storm, which may be connected to the advantages of Chinese medicine, including alleviating the effect, various targets, and overall regulation. The production of antiinflammatory cytokines and M2 macrophage polarization by PG2 have been demonstrated to be effective treatments for cytokine storms caused by COVID-19 lung injury [111].…”