Using bioinformatics and systems biology methods to identify the mechanism of interaction between COVID-19 and nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is considered a risk factor for severe COVID-19, but the mechanism remains unknown. This study used bioinformatics to help define the relationship between these diseases. The GSE147507 (COVID-19), GSE126848 (NAFLD), and GSE63067 (NAFLD-2) datasets were screened using the Gene Expression Omnibus. Common differentially expressed genes were then identified using a Venn diagram. Gene ontology analysis and KEGG pathway enrichment were performed on the differentially expressed genes. A protein-protein interaction network was also constructed using the STRING platform, and key genes were identified using the Cytoscape plugin. GES63067 was selected for validation of the results. Analysis of ferroptosis gene expression during the development of the 2 diseases and prediction of their upstream miRNAs and lncRNAs. In addition, transcription factors (TFs) and miRNAs related to key genes were identified. Effective drugs that act on target genes were found in the DSigDB. The GSE147507 and GSE126848 datasets were crossed to obtain 28 co-regulated genes, 22 gene ontology terms, 3 KEGG pathways, and 10 key genes. NAFLD may affect COVID-19 progression through immune function and inflammatory signaling pathways. CYBB was predicted to be a differential ferroptosis gene associated with 2 diseases, and the CYBB-hsa-miR-196a/b-5p-TUG1 regulatory axis was identified. TF-gene interactions and TF-miRNA coregulatory network were constructed successfully. A total of 10 drugs, (such as Eckol, sulfinpyrazone, and phenylbutazone) were considered as target drugs for Patients with COVID-19 and NAFLD. This study identified key gene and defined molecular mechanisms associated with the progression of COVID-19 and NAFLD. COVID-19 and NAFLD progression may regulate ferroptosis through the CYBB-hsa-miR-196a/b-5p-TUG1 axis. This study provides additional drug options for the treatment of COVID-19 combined with NAFLD disease.

Octyl gallate targeting the 3C-like protease exhibits highly efficient antiviral activity against swine enteric coronavirus PEDV.

Infection with porcine epidemic diarrhea virus (PEDV) causes severe watery diarrhea in newborn piglets, leading to substantial financial losses for the swine industry. In this study, we screened small molecule drugs targeting 3 C-like protease (3CLpro) by molecular docking, and further evaluated the antiviral activity of the screened drugs against PEDV. Results showed that octyl gallate (OG), a widely used food additive, exhibited strong binding affinity with the 3CLpro active sites of PEDV. Bio-layer interferometry and fluorescence resonance energy transfer revealed that OG directly interacts with PEDV 3CLpro (KD = 549 nM) and inhibits 3CLpro activity (IC50 = 22.15 µM). OG showed a strong inhibition of PEDV replication in vitro. Virus titers were decreased by 0.58 and 0.71 log10 TCID50/mL for the CV777 and HM2017 strains, respectively. In vivo, all piglets in the PEDV-infected group died at 48 h post-infection (hpi), while 75% of piglets in the OG treatment group showed significant relief from the clinical symptoms, pathological damage, and viral loads in the jejunum and ileum. Moreover, the western blotting results showed that OG also has strong antiviral activity against other swine enteric coronaviruses, including transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV). Our findings revealed that OG could be developed as a novel antiviral drug against PEDV. The OG exhibited a potential broad-spectrum antiviral drug for control of other swine enteric coronaviruses.

Effectiveness and safety review of Chinese herbal sachets for external use in the treatment of COVID-19 pandemic: A protocol for systematic review and meta-analysis.

BACKGROUND: COVID-19 has strong transmission power, and people are generally susceptible to it. Patients with weak constitution and low immunity function are more likely to be infected. Aromatic therapy of traditional Chinese medicine has the effect of inhibiting virus and sterilization, especially the external treatment of traditional Chinese medicine has played an important role in the fight against the epidemic situation. METHODS: Nine databases will be searched under the guideline of research strategy, from their inception to March 31, 2021, for relevant randomized controlled trial (RCTs) published. These databases are Cochrane Library, PubMed, EMBASE, Web of Science, ScienceDirect, China National Knowledge Infrastructure, Wan-fang Data, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. The types on Language of literature are English and Chinese. Researchers will independently operate the literature research, screening, quality evaluation, data collection, and data analysis with same research strategy and selection criteria. Methodological quality will be evaluated under the guideline of the Cochrane Collaboration's tool. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) will be used to determine confidence in the effect estimates. Meta-analysis or subgroup analysis will be performed according to the including data type. Meta-analysis will be performed with Stata 13.0 software. RESULTS: Outcome will be displayed by effective rates, quality of life score, adverse effect. CONCLUSION: This systematic review will provide evidence whether Chinese herbal sachets are effective and safe intervention of COVID-19 Pandemic. REGISTRATION NUMBER IN PROSPERO: CRD42021238580.

SARS-CoV-2 neutralizing antibody levels are correlated with severity of COVID-19 pneumonia.

The emerging coronavirus disease 2019 (COVID-19) has become a serious global public health threat. With more and more recovered patients, it is urgently needed for evaluation of the neutralizing antibody (NAb) in these patients. In this study, we collected blood samples from 49 patients recently recovered from COVID-19. Serum NAbs were measured using a novel surrogate virus neutralization test (sVNT). Factors associated with NAb titers were analyzed using Ordinary Least Squares regression model. The median age of the study participants was 37 years (IQR, 30.0-54.5) and 55.1 % (27/49) of which were male. The median time to blood collection (for NAb analysis) from illness onset, viral clearance and discharge were 43.0 days (IQR, 36.0-50.0), 27.0 days (IQR, 20.5-37) and 17.0 days (IQR, 15.0-33.0), respectively. Patients had a median NAb titer of 1: 40 (IQR, 1:15-1:120). NAbs were not detected in two asymptomatic children who quickly cleared the virus. NAb titers were higher in patients with older age (p = 0.020), symptomatic infection (p = 0.044), more profound lung involvement (p＜0.001), abnormal C-reactive protein level (p＜0.01) and elevated lactate dehydrogenase (p = 0.019). Multivariable analysis revealed that severity of pneumonia and having comorbidity positively correlated with NAb titers in recovered patients (p = 0.02), while use of corticosteroids negatively impacted NAb titers (p = 0.01). Our study suggests that some COVID-19 patients may not have detectable NAb after recovery. SARS-CoV-2 NAb titers are positively correlated with severity of COVID-19 pneumonia.

Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis.

The outbreak of the novel coronavirus disease (COVID-19) quickly spread all over China and to more than 20 other countries. Although the virus (severe acute respiratory syndrome coronavirus [SARS-Cov-2]) nucleic acid real-time polymerase chain reaction (PCR) test has become the standard method for diagnosis of SARS-CoV-2 infection, these real-time PCR test kits have many limitations. In addition, high false-negative rates were reported. There is an urgent need for an accurate and rapid test method to quickly identify a large number of infected patients and asymptomatic carriers to prevent virus transmission and assure timely treatment of patients. We have developed a rapid and simple point-of-care lateral flow immunoassay that can detect immunoglobulin M (IgM) and IgG antibodies simultaneously against SARS-CoV-2 virus in human blood within 15 minutes which can detect patients at different infection stages. With this test kit, we carried out clinical studies to validate its clinical efficacy uses. The clinical detection sensitivity and specificity of this test were measured using blood samples collected from 397 PCR confirmed COVID-19 patients and 128 negative patients at eight different clinical sites. The overall testing sensitivity was 88.66% and specificity was 90.63%. In addition, we evaluated clinical diagnosis results obtained from different types of venous and fingerstick blood samples. The results indicated great detection consistency among samples from fingerstick blood, serum and plasma of venous blood. The IgM-IgG combined assay has better utility and sensitivity compared with a single IgM or IgG test. It can be used for the rapid screening of SARS-CoV-2 carriers, symptomatic or asymptomatic, in hospitals, clinics, and test laboratories.