Geraniin as a potential inhibitor of SARS-CoV-2 3CLpro.

Geraniin is a polyphenolic compound first isolated from Geranium thunbergii. The major protease (Mpro), namely 3 C-like protease (3CLpro), of coronaviruses is considered an attractive drug target as it is essential for the processing and maturation of viral polyproteins. Thus, our primary goal is to explore the efficiency of geraniin on 3CLpro of SARS-CoV-2 using the computational biology strategy. In this work, we studied the anti-coronavirus effect of geraniin in vitro and its potential inhibitory mode against the 3CLpro of SARS-CoV-2. We found that geraniin inhibited HCoV-OC43 coronavirus-infected cells during the attachment and penetration phases. Molecular docking and dynamics simulations exhibited that geraniin had a strong binding affinity and high stable binding to 3CLpro of SARS-CoV-2. Geraniin showed a strong inhibitory activity on coronavirus and may be a potential inhibitor of SARS-CoV-2 3CLpro.

Puerarin reduces impairment of intestinal and adipose immune responses to influenza virus infection in mice.

Influenza is an acute viral respiratory disease that can also cause gastroenteritis-like symptoms, such as abdominal pain, nausea, vomiting, and diarrhea. Immune dysfunction of adipose tissue is involved in the occurrence and prognosis of influenza viral pneumonia. In this study, we analyzed intestinal and adipose immune responses in mice infected with influenza virus and found that the impairment of intestinal and adipose immunity to influenza virus infection could be reversed by treatment with puerarin, a medicinal compound isolated from Pueraria lobata (called "gegen" in Chinese). We found that the lungs, small intestines (duodenum, ileum, jejunum) and large intestines (colon and rectum) of infected mice showed obvious inflammatory lesions, with significantly increased levels of virus, inflammatory cytokines (interleukin [IL]-6, IL-17, and tumor necrosis factor-α), Toll-like receptors 3, 4, and 9, and integrin αvß3 and α4, and a decreased level of secreted IgA compared to the normal control group (NC) (P < 0.05-0.001). Influenza virus infected mesenteric lymph nodes and adipose tissue, and adipokines (leptin, visfatin, "chemerin", and adiponectin) of lung and mesenteric adipose tissue were dysregulated. Puerarin treatment reversed the impairment of the intestinal and adipose immune responses in mice infected with influenza virus. Our findings suggest that influenza virus can infect adipose tissue and lead to intestinal adipose immune dysfunction in normal-weight mice and that the impairment of the intestinal and adipose immune response to influenza virus infection can be reversed by puerarin treatment.

A potential antiviral activity of Esculentoside A against binding interactions of SARS-COV-2 spike protein and angiotensin converting enzyme 2 (ACE2).

The recent emergence of the novel coronavirus (SARS-CoV-2) has resulted in a devastating pandemic with global concern. However, to date, there are no regimens to prevent and treat SARS-CoV-2 virus. There is an urgent need to identify novel leads with anti-viral properties that impede viral pathogenesis in the host system. Esculentoside A (EsA), a saponin isolated from the root of Phytolacca esculenta, is known to exhibit diverse pharmacological properties, especially anti-inflammatory activity. To our knowledge, SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) to enter host cells. This is mediated through the proteins of SARS-CoV-2, especially the spike glycoprotein receptor binding domain. Thus, our primary goal is to prevent virus replication and binding to the host, which allows us to explore the efficiency of EsA on key surface drug target proteins using the computational biology paradigm approach. Here, the anti-coronavirus activity of EsA in vitro and its potential mode of inhibitory action on the S-protein of SARS-CoV-2 were investigated. We found that EsA inhibited the HCoV-OC43 coronavirus during the attachment and penetration stage. Molecular docking results showed that EsA had a strong binding affinity with the spike glycoprotein from SARS-CoV-2. The results of the molecular dynamics simulation revealed that EsA had higher stable binding with the spike protein. These results demonstrated that Esculentoside A can act as a spike protein blocker to inhibit SARS-CoV-2. Considering the poor bioavailability and low toxicity of EsA, it is suitable as novel lead for the inhibitor against binding interactions of SARS-CoV-2 of S-protein and ACE2.

Characterization of the complete chloroplast genome of toad lily Tricyrtis Macropoda (Liliaceae).

Tricyrtis (Liliaceae) is an endemic genus in East Asia. Many of the species in the genus are in Endangered condition due to habitat loss and extensive horticultural usage in recent decades. In present study, we reported the first Tricyrtis chloroplast (cp) genome, Tricyrtis macropoda, based on Illumina pair-end sequencing data. The complete chloroplast genome size is 155,778 bp. In total, 131 genes were identified, including 85 protein-coding genes, 8 rRNA genes, and 38 tRNA genes. Fifteen genes are containing introns (clpP and ycf3 contained two introns) and 14 genes had two copies. The overall GC content of this genome was 37.4%. A further phylogenomic analysis of Liliales, including 62 taxa, was conducted for the placement of genus Tricyrtis. The complete plastome of T. marcropoda will provide a valuable resource for further genetic conservation, phylogenomic, and evolution studies in the genus and family.

Expression changes and significance of eukaryocyte initiation factors-4E in esophageal carcinogenesis / 新乡医学院学报

Objective To explore the expression of eukaryocyte initiation factors-4E (eIF-4E) in normal esophageal epithelium and different esophageal lesions tissue and its relationship with vascular endothelial growth factor (VEGF).Methods Thirty normal esophageal incisal margin tissues,32 atypical hyperplasia tissues,20 carcinoma in situ tissues and 117 esophageal invasive carcinoma tissues were selected from the biopsy specimens of the Department of Pathology,the First Affiliated Hospital of Xinxiang Medical University from March 2014 to March 2016.The expression of eIF-4E and VEGF were detected by immunohistochemistry method and the correlation between them was analyzed.Results The positive expression rate of eIF-4E in normal esophageal epithelium,atypical hyperplasia,carcinoma in situ and invasive carcinoma tissues was 0.0％ (0/ 30),9.4％ (3/32),45.0％ (9/20) and 80.3％ (94/117) respectively.There was no statistic difference in the positive expression rate of eIF-4E in normal esophageal epithelium and atypical hyperplasia tissues (P ＞ 0.05);there was statistic difference in the positive expression rate of eIF-4E in the other esophageal tissues(P ＜ 0.05).In 117 invasive carcinoma tissues,the positive expression rate of eIF-4E in metastatic carcinoma tissues (93.2％,55/59) was significantly higher than that in the non metastatic carcinoma tissues (67.2％,39/58) (P ＜ 0.05).The positive expression rate of eIF-4E in esophageal carcinoma tissues which invaded into shallow muscle layer,deep muscular layer and adventitia was 70.0％ (28/40),73.8％ (31/42) and 100.0％ (35/ 35) respectively;there was no statistic difference in positive expression rate of eIF-4E in the carcinoma tissues which invaded into shallow muscle layer and deep muscular layer(P ＞ 0.05);the positive expression rate of eIF-4E in the carcinoma tissues which invaded into shallow muscle layer and deep muscular layer was significantly lower than that in the carcinoma tissues which invaded into adventitia(P ＜0.01).The expression of eIF-4E in the esophageal invasive carcinoma tissues was positive VEGF(x2 =51.460,P ＜ O.05).Conclusion eIF-4E play an important role in the canceration of normal esophageal and the invasion,metastasis of esophageal carcinoma.The expression of eIF-4E is correlate with VEGF in esophageal carcinoma tissues.