Isoliquiritigenin for COVID-19

Background/Objectives: Coronavirus disease 2019 (COVID-19) has been a global pandemic since 2019, but effective therapeutic treatments for it remain limited. Shuqing Granule (SG) is a traditional Chinese medicine containing ingredients such as indirubin, shinpterocarpin, naringenin, and quercetin. It exhibits anti-inflammatory and antiviral activities as well as broad-spectrum antiviral effects, yet its potential role in the treatment of COVID-19 remains unclear. This study thus aimed to explore the therapeutic effects of SG on COVID-19, with a focus on its potential anti-SARS-CoV-2 activity linked to these bioactive ingredients. Methods: The potential therapeutic ability of SG was investigated by combining network pharmacology, molecular docking, and experimental verification. First, key ingredients in SG and their corresponding targets, as well as COVID-19-related targets, were identified. Then, enrichment analyses were performed to highlight potential key pathways. Additionally, molecular docking was conducted to assess the binding capacity of the key ingredients to ACE2. Finally, experiments such as Western blot and ELISA were conducted to verify the effect of SG. Results: The results showed that 15 key ingredients such as quercetin in SG could affect overlapping targets such as RELA. Molecular docking results showed that key ingredients in SG, such as isoliquiritigenin, formononetin, shinpterocarpin, indirubin, naringenin, kaempferol, and 7-Methoxy-2-methylisoflavone, might bind to angiotensin-converting enzyme II (ACE2)—a critical receptor in the process of COVID-19 infection—thereby exerting antiviral effects. Experiments such as Western blot and ELISA further demonstrated that SG could reduce inflammation induced by the SARS-CoV-2 S1 protein by 50%. This effect might be achieved by downregulating ACE2 expression by 1.5 times and inhibiting the NF-κB signaling pathway. Conclusions: This study confirmed that SG has potential as a candidate for COVID-19 treatment. It also provided a new approach for the application of traditional Chinese medicine in combating the virus.

Abstract The COVID-19 pandemic, caused by SARS-CoV-2, has intensified the search for effective antiviral agents. This study investigates the inhibitory potential of 473 flavonoids from the genus Erythrina against the key enzyme of SARS-CoV-2, RNA-dependent RNA polymerase (RdRp). Virtual screening campaign using molecular docking identified 128 flavonoids with stronger binding energies to RdRp than remdesivir, a WHO-endorsed drug. Lipinski’s Rule of Five and ADMET profiling suggested butein (119) as the promising RdRp inhibitor. Moreover, molecular dynamics simulations revealed that 119 binds effectively to RdRp and interacts with the RNA template and primer, suggesting a multi-faceted inhibitory mechanism. Our findings highlight the potential of Erythrina-derived flavonoids, particularly compound 119, as potent RdRp inhibitors, warranting further experimental studies.

Many inflammatory mechanisms are involved in the pathophysiology of COVID-19 infection. COVID-19 inhibits IFN antiviral responses, so we should expect an out-of-control viral replication. “Cytokine storms” occur due to the over-production of pro-inflammatory cytokines after an influx of neutrophils and monocytes/macrophages and may be responsible for the immunopathology of the lung involvement. Several cascades have been reported in the activation process of NF-κB. In this paper, to find new therapeutic options for COVID-19 infection, we reviewed some natural products that could potentially inhibit the NF-κB pathway. We found that sevoflurane, quercetin, resveratrol, curcumin, KIOM-C, bergenin, garcinia kola, shenfu, piperlongumine, wogonin, oroxylin, plantamajoside, naringin, ginseng, kaempferol, allium sativum L, illicium henryi, isoliquiritigenin, lianhua qingwen, magnoflorine, and ma Huang Tang might be effective in inhibiting the NF-KB pathway. These natural products could be helpful in the control of COVID-19 infections. However, larger clinical trials are needed to ascertain the efficacy of these products fully.