Prediction and Verification of Curcumin as a Potential Drug for Inhibition of PDCoV Replication in LLC-PK1 Cells.

Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus (CoV) that causes lethal watery diarrhea in neonatal pigs and poses economic and public health burdens. Currently, there are no effective antiviral agents against PDCoV. Curcumin is the active ingredient extracted from the rhizome of turmeric, which has a potential pharmacological value because it exhibits antiviral properties against several viruses. Here, we described the antiviral effect of curcumin against PDCoV. At first, the potential relationships between the active ingredients and the diarrhea-related targets were predicted through a network pharmacology analysis. Twenty-three nodes and 38 edges were obtained using a PPI analysis of eight compound-targets. The action target genes were closely related to the inflammatory and immune related signaling pathways, such as the TNF signaling pathway, Jak-STAT signaling pathway, and so on. Moreover, IL-6, NR3C2, BCHE and PTGS2 were identified as the most likely targets of curcumin by binding energy and 3D protein-ligand complex analysis. Furthermore, curcumin inhibited PDCoV replication in LLC-PK1 cells at the time of infection in a dose-dependent way. In poly (I:C) pretreated LLC-PK1 cells, PDCoV reduced IFN-ß production via the RIG-I pathway to evade the host's antiviral innate immune response. Meanwhile, curcumin inhibited PDCoV-induced IFN-ß secretion by inhibiting the RIG-I pathway and reduced inflammation by inhibiting IRF3 or NF-κB protein expression. Our study provides a potential strategy for the use of curcumin in preventing diarrhea caused by PDCoV in piglets.

25-Hydroxycholesterol Mediates Cholesterol Metabolism to Restrict Porcine Deltacoronavirus Infection via Suppression of Transforming Growth Factor ß1.

Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus in pigs, is one of the major pathogens for lethal watery diarrhea in piglets and poses a threat to public health because of its potential for interspecies transmission to humans. 25-Hydroxycholesterol (25HC), a derivative of cholesterol, exhibits multiple potential modulating host responses to pathogens, including viruses and bacteria, as well as pathogen-induced inflammation, while its antiviral effect on PDCoV and how it mediates the biological process of host cells to counter against infections remain poorly understood. Here, we thoroughly explored the antiviral effect of 25HC on PDCoV infection and tried to elucidate the underlying mechanisms. 25HC showed no toxic effect in LLC-PK1 cells and exerted antiviral ability against PDCoV infection in vitro. The viral cycle and time-of-addition analyses showed that 25HC mainly restricted the early and middle periods of the PDCoV postentry stage to inhibit infection. 25HC regulated disordered cholesterol metabolism induced by PDCoV infection and stimulated interferon-related lipid droplet accumulation. Transforming growth factor ß1 (TGF-ß1), screened by bioinformatic analyses, seemed to play an important role in PDCoV infection and was downregulated by 25HC. One interesting finding is that inhibition of TGF-ß1 with the inhibitor asiaticoside exhibited a similar antiviral capacity to 25HC and demonstrated regulation of cholesterol metabolism. Taking all of the findings together, we verified the antiviral effect of 25HC on PDCoV through interference with cholesterol metabolism, which may be related to its suppression of TGFß1. IMPORTANCE As an emerging enteropathogenic coronavirus in pigs, porcine deltacoronavirus (PDCoV) causes giant economic loss in the pig industry because of lethal diarrhea and possesses the potential for transmission from animals to humans. Several pieces of evidence have suggested the antiviral potential of cholesterol-25-hydroxylase and importance of cholesterol in viral infection. This study reports that 25-hydroxycholesterol (25HC) significantly restricted PDCoV infection through modulation of cholesterol metabolism, and we identified that lipid droplets play important roles in interferon response against virus infection. Moreover, this study identified the importance of TGF-ß1 in CoV infection by bioinformatic analysis and verified that the inhibition of TGF-ß1 showed anti-PDCoV capacity. Moreover, we uncovered the relationship between TGF-ß and cholesterol metabolism initially. Given that the importance of cholesterol in viral infection, 25HC has a great potential to treat PDCoV infection and TGF-ß1 can be a crucial antiviral target.

The effects of narrative exposure therapy on COVID-19 patients with post-traumatic stress symptoms: A randomized controlled trial.

BACKGROUND: With the global attack of Coronavirus Disease 2019 (COVID-19), cases with Post-traumatic Stress Disorder (PTSD) have been increasing steadily, which seriously affects the quality of life of patients and as such, seeking effective treatments is an urgent matter. Narrative Exposure Therapy (NET) is a typical cognitive behavioral therapy targeting trauma-related psychological disorders and may be an effective intervention. METHODS: A total of 111 COVID-19 patients near the discharge stage with positive screening results for posttraumatic stress symptoms (PTSS) were randomly assigned (1:1) to either the study group or the control group. The study group received NET and personalized psychological intervention, while the control group only received personalized psychological intervention. PTSS, depression, anxiety and sleep quality were measured pre- and post-intervention to evaluate the effect of NET. This trial was registered with the International Standard Randomized Clinical Trial Registry (No. ChiCTR2000039369). RESULTS: NET participants showed a significantly greater PTSS reduction in comparison with the control group after the intervention. Improvement in sleep quality, anxiety and depression after the intervention were pronounced but not significantly different between the two treatment groups. LIMITATIONS: The assessors weren't blinded for the convenience of measurement and protection of participants' psychological security. CONCLUSIONS: NET likely had a positive impact on PTSS of COVID-19 patients. Clinical staff should consider applying NET to improve the psychological well-being of patients who have experienced an epidemic such as COVID-19.

The Risk Factors for the Exacerbation of COVID-19 Disease: A Case-control Study.

AIMS AND OBJECTIVES: To investigate the factors associated with the exacerbations of COVID-19. BACKGROUND: At present, COVID-19 is prevalent in the world, seriously endangering the property and life safety of people around the world. Currently, there are many reports on the clinical features, complications and risk factors of death of COVID-19, but there are few reports on the factors associated with the exacerbation of COVID-19. DESIGN: Case-control Study. METHODS: Patients with COVID-19 were recruited from four designated hospitals for novel coronavirus pneumonia in Xiangyang City, Hubei Province from January to April 2020. The patients were divided into disease exacerbation group (n = 53) and disease stabilisation group (n = 265) according to the disease progression during hospitalisation. Univariate analysis and multivariate logistic regression were used to identify the factors associated with the exacerbation of COVID-19. The research was reported according to STROBE statement. RESULTS: Univariate analysis showed there were significant differences in gender, age, hypertension, heart disease, kidney disease, white blood cell count, percentage of neutrophil, percentage of lymphocyte, C-reactive protein, lactate dehydrogenase, total protein, albumin, creatinine, calcium ion, rate of erythrocyte sedimentation, cough, expectoration, chest tightness, gastrointestinal discomfort and dyspnoea between the two groups. The variables with p < 0.05 in the aforementioned difference analysis were included in binary logistic regression analysis, which showed that age, hypertension history, chest tightness, percentage of neutrophil, percentage of lymphocyte, lactate dehydrogenase and creatinine were independent factors associated with COVID-19 disease exacerbation. CONCLUSION: Clinicians may warn the exacerbation of COVID-19 facing above risk factors and associated characteristics, and adjust the diagnosis and treatment plan to delay the disease progression, reduce complications and mortality and improve the prognosis of patients. RELEVANCE TO CLINICAL PRACTICE: Patients with certain risk factors associated with COVID-19 diseases exacerbation should be observed and targeted by using effective early interventions.