Exploring the mechanism of action of licorice in the treatment of COVID-19 through bioinformatics analysis and molecular dynamics simulation.

Purpose: The rapid worldwide spread of Corona Virus Disease 2019 (COVID-19) has become not only a global challenge, but also a lack of effective clinical treatments. Studies have shown that licorice can significantly improve clinical symptoms such as fever, dry cough and shortness of breath in COVID-19 patients with no significant adverse effects. However, there is still a lack of in-depth analysis of the specific active ingredients of licorice in the treatment of COVID-19 and its mechanism of action. Therefore, we used molecular docking and molecular dynamics to explore the mechanism of action of licorice in the treatment of COVID-19. Methods: We used bioinformatics to screen active pharmaceutical ingredients and potential targets, the disease-core gene target-drug network was established and molecular docking was used for verification. Molecular dynamics simulations were carried out to verify that active ingredients were stably combined with protein targets. The supercomputer platform was used to measure and analyze stability of protein targets at the residue level, solvent accessible surface area, number of hydrogen bonds, radius of gyration and binding free energy. Results: Licorice had 255 gene targets, COVID-19 had 4,628 gene targets, the intersection gene targets were 101. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene ontology (GO) analysis showed that licorice played an important role mainly through the signaling pathways of inflammatory factors and oxidative stress. Molecular docking showed that Glycyrol, Phaseol and Glyasperin F in licorice may playe a role in treating COVID-19 by acting on STAT3, IL2RA, MMP1, and CXCL8. Molecular dynamics were used to demonstrate and analyze the binding stability of active ingredients to protein targets. Conclusion: This study found that Phaseol in licorice may reduce inflammatory cell activation and inflammatory response by inhibiting the activation of CXCL8 and IL2RA; Glycyrol may regulate cell proliferation and survival by acting on STAT3. Glyasperin F may regulate cell growth by inhibiting the activation of MMP1, thus reducing tissue damage and cell death caused by excessive inflammatory response and promoting the growth of new tissues. Therefore, licorice is proposed as an effective candidate for the treatment of COVID-19 through STAT3, IL2RA, MMP1, and CXCL8.

Mechanism of N-0385 blocking SARS-CoV-2 to treat COVID-19 based on molecular docking and molecular dynamics.

Purpose: 2019 Coronavirus disease (COVID-19) has caused millions of confirmed cases and deaths worldwide. TMPRSS2-mediated hydrolysis and maturation of spike protein is essential for SARS-CoV-2 infection in vivo. The latest research found that a TMPRSS2 inhibitor called N-0385 could effectively prevent the infection of the SARS-CoV-2 and its variants. However, it is not clear about the mechanism of N-0385 treatment COVID-19. Therefore, this study used computer simulations to investigate the mechanism of N-0385 treatment COVID-19 by impeding SARS-CoV-2 infection. Methods: The GeneCards database was used to search disease gene targets, core targets were analyzed by PPI, GO and KEGG. Molecular docking and molecular dynamics were used to validate and analyze the binding stability of small molecule N-0385 to target proteins. The supercomputer platform was used to simulate and analyze the number of hydrogen bonds, binding free energy, stability of protein targets at the residue level, radius of gyration and solvent accessible surface area. Results: There were 4,600 COVID-19 gene targets from GeneCards database. PPI, GO and KEGG analysis indicated that signaling pathways of immune response and inflammation played crucial roles in COVID-19. Molecular docking showed that N-0385 could block SARS-CoV-2 infection and treat COVID-19 by acting on ACE2, TMPRSS2 and NLRP3. Molecular dynamics was used to demonstrate that the small molecule N-0385 could form very stable bindings with TMPRSS2 and TLR7. Conclusion: The mechanism of N-0385 treatment COVID-19 was investigated by molecular docking and molecular dynamics simulation. We speculated that N-0385 may not only inhibit SARS-CoV-2 invasion directly by acting on TMPRSS2, ACE2 and DPP4, but also inhibit the immune recognition process and inflammatory response by regulating TLR7, NLRP3 and IL-10 to prevent SARS-CoV-2 invasion. Therefore, these results suggested that N-0385 may act through multiple targets to reduce SARS-CoV-2 infection and damage caused by inflammatory responses.

Mechanism of N-0385 blocking SARS-CoV-2 to treat COVID-19 based on molecular docking and molecular dynamics

Purpose 2019 Coronavirus disease (COVID-19) has caused millions of confirmed cases and deaths worldwide. TMPRSS2-mediated hydrolysis and maturation of spike protein is essential for SARS-CoV-2 infection in vivo. The latest research found that a TMPRSS2 inhibitor called N-0385 could effectively prevent the infection of the SARS-CoV-2 and its variants. However, it is not clear about the mechanism of N-0385 treatment COVID-19. Therefore, this study used computer simulations to investigate the mechanism of N-0385 treatment COVID-19 by impeding SARS-CoV-2 infection. Methods The GeneCards database was used to search disease gene targets, core targets were analyzed by PPI, GO and KEGG. Molecular docking and molecular dynamics were used to validate and analyze the binding stability of small molecule N-0385 to target proteins. The supercomputer platform was used to simulate and analyze the number of hydrogen bonds, binding free energy, stability of protein targets at the residue level, radius of gyration and solvent accessible surface area. Results There were 4,600 COVID-19 gene targets from GeneCards database. PPI, GO and KEGG analysis indicated that signaling pathways of immune response and inflammation played crucial roles in COVID-19. Molecular docking showed that N-0385 could block SARS-CoV-2 infection and treat COVID-19 by acting on ACE2, TMPRSS2 and NLRP3. Molecular dynamics was used to demonstrate that the small molecule N-0385 could form very stable bindings with TMPRSS2 and TLR7. Conclusion The mechanism of N-0385 treatment COVID-19 was investigated by molecular docking and molecular dynamics simulation. We speculated that N-0385 may not only inhibit SARS-CoV-2 invasion directly by acting on TMPRSS2, ACE2 and DPP4, but also inhibit the immune recognition process and inflammatory response by regulating TLR7, NLRP3 and IL-10 to prevent SARS-CoV-2 invasion. Therefore, these results suggested that N-0385 may act through multiple targets to reduce SARS-CoV-2 infection and damage caused by inflammatory responses.

Efficacy and safety of recanalization therapy for acute ischemic stroke with COVID-19: A systematic review and meta-analysis.

Background: The novel coronavirus disease 2019 (COVID-19) has rapidly spread worldwide and created a tremendous threat to global health. Growing evidence suggests that patients with COVID-19 have more severe acute ischemic stroke (AIS). However, the overall efficacy and safety of recanalization therapy for AIS patients infected by the SARS-CoV-2 virus is unknown. Methods: The PRISMA guideline 2020 was followed. Two independent investigators systematically searched databases and ClinicalTrials.gov to identify relevant studies published up to 31 March 2022. AIS patients who received any recanalization treatments were categorized into those with COVID-19 and those without COVID-19. The main efficacy outcomes were patients' functional independence on discharge and successful recanalization, and the safety outcomes were in-hospital mortality and symptomatic intracranial hemorrhage. Subgroup analyses were implemented to assess the influence of admission National Institutes of Health Stroke Scale and different recanalization treatments on the outcomes. STATA software 12.0 was used for the statistical analysis. Results: This systematic review and meta-analysis identified 10 studies with 7,042 patients, including 596 COVID-19 positive patients and 6,446 COVID-19 negative patients. Of the total patients, 2,414 received intravenous thrombolysis while 4,628 underwent endovascular thrombectomy. COVID-19 positive patients had significantly lower rates of functional independence at discharge [odds ratio (OR) 0.30, 95% confidence interval (CI) 0.15 to 0.59, P = 0.001], lower rates of successful recanalization (OR 0.40, 95% CI 0.24 to 0.68, P = 0.001), longer length of hospital stay (weighted mean difference 5.09, 95% CI 1.25 to 8.94, P = 0.009) and higher mortality rates (OR 3.38, 95% CI 2.43 to 4.70, P < 0.0001). Patients with COVID-19 had a higher risk of symptomatic intracranial hemorrhage than the control group, although the difference did not reach statistical significance (OR 2.34, 95% CI 0.99 to 5.54, P = 0.053). Conclusions: Compared with COVID-19 negative AIS patients who received recanalization treatments, COVID-19 positive patients turned out to have poorer outcomes. Particular attention needs to be paid to the treatments for these COVID-19 patients to decrease mortality and morbidity. Long-term follow-up is necessary to evaluate the recanalization treatments for AIS patients with COVID-19. Systematic review registration: https://inplasy.com/inplasy-2022-4-0022/, identifier: INPLASY202240022.

Exploring the mechanism of action of licorice in the treatment of COVID-19 through bioinformatics analysis and molecular dynamics simulation

The mechanisms analysis of licorice in the treatment of COVID-19.

Using a graph-based image segmentation algorithm for remote vital sign estimation and monitoring.

Reliable and contactless measurements of vital signs, such as respiration and heart rate, are still unmet needs in clinical and home settings. Mm-wave radar and video-based technologies are promising, but currently, the signal processing-based vital sign extraction methods are prone to body motion disruptions or illumination variations in the surrounding environment. Here we propose an image segmentation-based method to extract vital signs from the recorded video and mm-wave radar signals. The proposed method analyses time-frequency spectrograms obtained from Short-Time Fourier Transform rather than individual time-domain signals. This leads to much-improved robustness and accuracy of the heart rate and respiration rate extraction over existing methods. The experiments were conducted under pre- and post-exercise conditions and were repeated on multiple individuals. The results are evaluated by using four metrics against the gold standard contact-based measurements. Significant improvements were observed in terms of precision, accuracy, and stability. The performance was reflected by achieving an averaged Pearson correlation coefficient (PCC) of 93.8% on multiple subjects. We believe that the proposed estimation method will help address the needs for the increasingly popular remote cardiovascular sensing and diagnosing posed by Covid-19.

Exploring the mechanism of action of Xuanfei Baidu granule (XFBD) in the treatment of COVID-19 based on molecular docking and molecular dynamics.

Purpose: The Corona Virus Disease 2019 (COVID-19) pandemic has become a challenge of world. The latest research has proved that Xuanfei Baidu granule (XFBD) significantly improved patient's clinical symptoms, the compound drug improves immunity by increasing the number of white blood cells and lymphocytes, and exerts anti-inflammatory effects. However, the analysis of the effective monomer components of XFBD and its mechanism of action in the treatment of COVID-19 is currently lacking. Therefore, this study used computer simulation to study the effective monomer components of XFBD and its therapeutic mechanism. Methods: We screened out the key active ingredients in XFBD through TCMSP database. Besides GeneCards database was used to search disease gene targets and screen intersection gene targets. The intersection gene targets were analyzed by GO and KEGG. The disease-core gene target-drug network was analyzed and molecular docking was used for verification. Molecular dynamics simulation verification was carried out to combine the active ingredient and the target with a stable combination. The supercomputer platform was used to measure and analyze the number of hydrogen bonds, the binding free energy, the stability of protein target at the residue level, the solvent accessible surface area, and the radius of gyration. Results: XFBD had 1308 gene targets, COVID-19 had 4600 gene targets, the intersection gene targets were 548. GO and KEGG analysis showed that XFBD played a vital role by the signaling pathways of immune response and inflammation. Molecular docking showed that I-SPD, Pachypodol and Vestitol in XFBD played a role in treating COVID-19 by acting on NLRP3, CSF2, and relieve the clinical symptoms of SARS-CoV-2 infection. Molecular dynamics was used to prove the binding stability of active ingredients and protein targets, CSF2/I-SPD combination has the strongest binding energy. Conclusion: For the first time, it was found that the important active chemical components in XFBD, such as I-SPD, Pachypodol and Vestitol, reduce inflammatory response and apoptosis by inhibiting the activation of NLRP3, and reduce the production of inflammatory factors and chemotaxis of inflammatory cells by inhibiting the activation of CSF2. Therefore, XFBD can effectively alleviate the clinical symptoms of COVID-19 through NLRP3 and CSF2.

Network Structure Features and Influencing Factors of Tourism Flow in Rural Areas: Evidence from China

Exploring the spatial network structure of tourism flow and its influencing factors is of great significance to the transmission of characteristic culture and the sustainable development of tourism in tourist destinations, especially in backward rural areas. Taking Qiandongnan Miao and Dong Autonomous Prefecture (hereinafter referred to as Qiandongnan Prefecture) as an example, this paper adopts social network analysis and Quadratic Assignment Procedure regression analysis to study the network structural characteristics and influencing factors of tourism flow using online travel blog data. The results show that: (1) There are seasonal changes in tourism flow, but the attractions that tourists pay attention to do not change with the seasons. (2) The tightness of the tourism flow network structure is poor. The core nodes are unevenly distributed, and there are obvious structural holes. (3) The density of the tourism flow network is low. There is a clear core–periphery structure in the network, and the core area has a weak driving effect on the periphery area. There are more cohesive subgroups in the network, but the degree of connectedness between the subgroups varies greatly. (4) Geographical adjacency, transportation accessibility, and tourism resource endowment influence tourism flow network structure. The study found that the influencing factors of tourism flow in rural areas are different from those in urban areas. These results provide useful information for the marketing and development of tourism management departments in rural areas.

Analysis of Epidemic Characteristics and Related Pathogenic Factors of 2726 Cases of Pityriasis Alba.

PURPOSE: To understand the distribution characteristics of onset time, onset age and gender of pityriasis alba (PA) patients in the dermatology clinic of our hospital and to further explore the pathogenesis of the disease to provide a scientific basis for the prevention and treatment of this disease. PATIENTS AND METHODS: The clinical data of 2726 outpatients with PA diagnosed for the first time from January 2016 to December 2020 were collected and descriptively analyzed. RESULTS: The number of patients with PA was less from January to March. The peak was reached in July and August. The number of cases affected by the COVID-19 epidemic in 2020 was significantly lower than that in previous years. Furthermore, the onset age of the patients ranged from 0 to 64 years old, and the median age of the total population was 7 (3, 13) years old, including 1566 males (57.45%) and 1160 females (42.55%). The ratio of male to female was 1.35:1. The number of male patients before 18 years old was higher than that of female patients, especially in the high paroxysmal age group. CONCLUSION: PA can be seen all the year round, and the onset peak of the disease is from July to August every year. It occurs frequently at the age of 1 to 14 before puberty. In the season of high incidence of PA, the protection from sun and moisture retention should be strengthened for infants and adolescents.