Oxalic acid blocked the binding of spike protein from SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variants to human angiotensin-converting enzymes 2.

An epidemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. Moreover, the emergence of SARS-CoV-2 variants of concern, such as Delta and Omicron, has seriously challenged the application of current therapeutics including vaccination and drugs. Relying on interaction of spike protein with receptor angiotensin-converting enzymes 2 (ACE2), SARS-CoV-2 successfully invades to the host cells, which indicates a strategy that identification of small-molecular compounds to block the entry is of great significance for COVID-19 prevention. Our study evaluated the potential efficacy of natural compound oxalic acid (OA) as an inhibitory agent against SARS-CoV-2 invasion, particular on the interaction of the receptor binding domain (RBD) of Delta and Omicron variants to ACE2. By employing a competitive binding assay in vitro, OA significantly blocked the binding of RBDs from Delta B.1.617.2 and Omicron B.1.1.529 to ACE2, but has no effect on the wide-type SARS-CoV-2 strain. Furthermore, OA inhibited the entries of Delta and Omicron pseudovirus into ACE2 high expressing-HEK293T cells. By surface plasmon resonance (SPR) assay, the direct bindings of OA to RBD and ACE2 were analyzed and OA had both affinities with RBDs of B.1.617.2 and B.1.1.529 and with ACE2. Molecular docking predicted the binding sites on the RBD-ACE2 complex and it showed similar binding abilities to both complex of variant Delta or Omicron RBD and ACE2. In conclusion, we provided a promising novel small-molecule compound OA as an antiviral candidate by blocking the cellular entries of SARS-CoV-2 variants.

Luteolin inhibits spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) binding to angiotensin-converting enzyme 2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a respiratory illness that poses a serious threat to global public health. In an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike (S) protein to engage with angiotensin-converting enzyme 2 (ACE2) in host cells. Chinese herbal medicines and their active components exhibit antiviral activity, with luteolin being a flavonoid that can significantly inhibit SARS-CoV infection. However, whether it can block the interaction between the S-protein RBD of SARS-CoV-2 and ACE2 has not yet been elucidated. Here, we investigated the effects of luteolin on the binding of the S-protein RBD to ACE2. By employing a competitive binding assay in vitro, we found that luteolin significantly blocked the binding of S-protein RBD to ACE2 with IC50 values of 0.61 mM, which was confirmed by the neutralized infection with SARS-CoV-2 pseudovirus in vivo. A surface plasmon resonance-based competition assay revealed that luteolin significantly affects the binding of the S-protein RBD to the ACE2 receptor. Molecular docking was performed to predict the binding sites of luteolin to the S-protein RBD-ACE2 complex. The active binding sites were defined based on published literature, and we found that luteolin might interfere with the mixture at residues including LYS353, ASP30, and TYR83 in the cellular ACE2 receptor and GLY496, GLN498, TYR505, LEU455, GLN493, and GLU484 in the S-protein RBD. These residues may together form attractive charges and destroy the stable interaction of S-protein RBD-ACE2. Luteolin also inhibits SARS-CoV-2 spike protein-induced platelet spreading, thereby inhibiting the binding of the spike protein to ACE2. Our results are the first to provide evidence that luteolin is an anti-SARS-CoV-2 agent associated with interference between viral S-protein RBD-ACE2 interactions.

Potential treatment of COVID-19 with traditional chinese medicine: What herbs can help win the battle with SARS-CoV-2?

Traditional Chinese medicine (TCM) has been successfully applied worldwide in the treatment of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the pharmacological mechanisms underlying this success remain unclear. Hence, the aim of this review is to combine pharmacological assays based on the theory of TCM in order to elucidate the potential signaling pathways, targets, active compounds, and formulas of herbs that are involved in the TCM treatment of COVID-19, which exhibits combatting viral infections, immune regulation, and amelioration of lung injury and fibrosis. Extensive reports on target screening are elucidated using virtual prediction via docking analysis or network pharmacology based on existing data. The results of these reports indicate that an intricate regulatory mechanism is involved in the pathogenesis of COVID-19. Therefore, more pharmacological research on the natural herbs used in TCM should be conducted in order to determine the association between TCM and COVID-19 and account for the observed therapeutic effects of TCM against COVID-19.

Network pharmacology analysis on mechanisms of xuanfei baidu prescription in treatment of SARS, MERS and COVID-19

Objective: To explore the effective components, target and signal pathway of Xuanfei Baidu Prescription in treatment of coronavirus infection, and to explain its mechanism of action. Methods A network of Character, taste, and meridian of Xuanfei Baidu Prescription was constructed using Cytoscape. Effective components and related targets of Xuanfei Baidu Prescription were selected by using TCMSP database, SwissADME database, and Swiss Target Prediction database. Disease targets of SARS, MERS and COVID-19 were collected using GeneCards database and CTD database. Drug targets and disease targets were intersected, and Cytoscape software was used to construct the network diagram. Using String database, the network model of protein-protein interaction (PPI) was constructed for potential targets. Metascape database was used for GO and KEGG enrichment analysis of potential targets, and Cytoscape was used to construct the network diagram. Results The results showed that 10 ingredients in Xuanfeibaidu Prescription are associated with the Lung meridian. 167 active components and 242 potential targets were screened out. The core drugs were Glycyrrhiza uralensis Fisch.,Ephedrae Herba, Artemisia annua L, Verbena officinalis L., Polygonum cuspidatum Sieb. et Zucc.. The core components were quercetin, stigmasterol, kaempferol, luteolin, isorhamnetin. The core targets were AKT1, IL-6, TP53, VEGFA, TNF. The possible mechanism of action is related to several signaling pathways such as PI3K-Akt signaling pathway, HIF-1 signaling pathway, TNF signaling pathway, and so on. Conclusion This study explored the potential common mechanism of Xuanfei Baidu Prescription on SARS, MERS and COVID-19, reflecting the multi-component, multi-target and multi-pathway characteristics of TCM.

Prevention of Cyclophosphamide-Induced Immunosuppression in Mice With Traditional Chinese Medicine Xuanfei Baidu Decoction.

Background and aims: Xuanfei Baidu decoction (XFBD), a traditional Chinese medicine formulation, was designed and successfully applied for COVID-19 disease treatment in China, while the mechanism is still not clear. Methods: To evaluate the protective effect of XFBD on immunosuppression in cyclophosphamide (CY)-treated mice, XFBD was orally administrated, the body weight was measured, and the immune organ index was calculated. HE staining was performed to analyze the pathological structures of the liver, spleen, and thymus. The levels of cytokines and immunoglobulin in the serum and spleen were evaluated by ELISA and RT-PCR. Splenic lymphocytes were isolated, and LPS-stimulated cell proliferation and the number of CD4+ and CD8+ T lymphocytes were evaluated. Results: XFBD significantly suppressed body weight loss and increased the indices of spleen and thymus. The pathological alteration was much improved after XFBD administration. The reductions of TNF-α, IFN-γ, IgG, and IgM levels in serum and IL-2, IL-4, and IL-6 expressions in the spleen were all significantly alleviated by XFBD. Splenic lymphocyte proliferation in response to LPS was further enhanced after treatment with XFBD. The reduction of CD4+ and CD8+ T lymphocytes in CY-treated mice was also highly increased in XFBD groups. Conclusion: Our findings suggested that XFBD played a crucial role in protection against immunosuppression in CY-treated mice and could be a potential candidate for immune modification and therapy.

Tracking social media during the COVID-19 pandemic: The case study of lockdown in New York State.

Facing the COVID-19 pandemic, governments have implemented a wide range of policies to contain the spread of the virus. During the pandemic, large amounts of COVID-19-related tweets emerge every day. Real-time processing of daily tweets may offer insights for monitoring public opinion about intervention measures implemented. In this work, lockdown policy in New York State has been set as a target of public opinion research. This task includes two stages, stance detection and opinion monitoring. For the stance detection stage, we explored several combinations of different text representations and classification algorithms, finding that the combination of Long Short-Term Memory (LSTM) with Global Vectors for Word Representation (GloVe) outperforms others. Due to the shortage of labeled data, we adopted the data distillation method for the training data augmentation. The augmentation of the training data allows to improve the performance of the model with a very small amount of manually-labeled data. After applying the distillation method, the accuracy of the model has been significantly improved. Utilizing the enhanced model, automatically classified tweets are analyzed over time to monitor the public opinion. By exploring the tweets in New York from January 22nd until September 30th, 2020, we show the correlation of public opinion with COVID-19 cases and mortality data, and the effect of government responses on the opinion shift. These results demonstrate the capability of the presented method to effectively and efficiently monitor public opinion during a pandemic.

[Recent advances in treatment of viral pneumonia using Chinese patent medicine].

Viral pneumonia is caused by a spreading of lung infection caused by respiratory viruses. Some virus infections were found to be highly aggressive, leading to lung inflammation and severe damage in respiratory system with high fatality rate. Currently, there is no effective therapeutic drugs in the clinic. The common clinical symptoms of viral pneumonias include fever, rhinitis, runny nose, nonproductive cough, fatigue, myalgias and headaches after the immune system being tricked by driving cytokines and overactivated immune response induced by cytokine storms. Patients with severe symptoms could get persistent high fever, dysfunctional breathing, consciousness disorders and even respiratory failure, post-inflammatory pulmonary fibrosis, multi-organ damages, shock and so on. Most clinical treatments are used to inhibit virus replication, relieve symptoms, inhibit excessive inflammatory response, regulate immune balance and protect organs. Both applied and basic research demonstrate that Chinese patent medicine has certain anti-viral effects, effectively inhibiting viral pneumonia transiting from mild to severe, rapid relieving of patient symptoms because of their multi-component and multi-target integrated roles. This review has summarized the reports on the treatment of viral pneumonia. Based on the pathogenic characteristics of viral pneumonia, this paper summarizes the diverse roles of the marketed Chinese patent medicine, such as their effects in inhibiting the progress of viral replication and overactivated inflammatory response, regulating immune balance, attenuating pulmonary fibrosis and so forth. Our paper summarizes the advantages of Chinese patient medicine in the treatment of viral pneumonia, based on which improvements of clinical therapy are expected to be made soon.