Extracellular Disintegration of Viral Proteins as an Innovative Strategy for Developing Broad-Spectrum Antivirals Against Coronavirus

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has claimed millions of lives and caused innumerable economic losses worldwide. Unfortunately, state-of-the-art treatments still lag behind the continual emergence of new variants. Key to resolving this issue is developing antivirals to deactivate coronaviruses regardless of their structural evolution. Here, we report an innovative antiviral strategy involving extracellular disintegration of viral proteins with hyperanion-grafted enediyne (EDY) molecules. The core EDY generates reactive radical species and causes significant damage to the spike protein of coronavirus, while the hyperanion groups ensure negligible cytotoxicity of the molecules. The EDYs exhibit antiviral activity down to nanomolar concentrations, and the selectivity index of up to 20,000 against four kinds of human coronavirus, including the SARS-CoV-2 Omicron variant, suggesting the high potential of this new strategy in combating the COVID-19 pandemic and a future "disease X."

Machine Learning-Based Scoring System for Early Prognosis Evaluation of Patients with Coronavirus Disease 2019

Background The global spread of coronavirus disease 2019 (COVID-19) continues to threaten human health security, exerting considerable pressure on healthcare systems worldwide. While prognostic models for COVID-19 hospitalized or intensive care patients are currently available, prognostic models developed for large cohorts of thousands of individuals are still lacking. Methods Between February 4 and April 16, 2020, we enrolled 3,974 patients admitted with COVID-19 disease in the Wuhan Huo-Shen-Shan Hospital and the Maternal and Child Hospital, Hubei Province, China. (1) Screening of key prognostic factors: A univariate Cox regression analysis was performed on 2,649 patients in the training set, and factors affecting prognosis were initially screened. Subsequently, a random survival forest model was established through machine analysis to further screen for factors that are important for prognosis. Finally, multivariate Cox regression analysis was used to determine the synergy among various factors related to prognosis. (2) Establishment of a scoring system: The nomogram algorithm established a COVID-19 patient death risk assessment scoring system for the nine selected key prognostic factors, calculated the C index, drew calibration curves and drew training set patient survival curves. (3) Verification of the scoring system: The scoring system assessed 1,325 patients in the test set, splitting them into high- and low-risk groups, calculated the C-index, and drew calibration and survival curves. Results The cross-sectional study found that age, clinical classification, sex, pulmonary insufficiency, hypoproteinemia, and four other factors (underlying diseases: blood diseases, malignant tumor;complications: digestive tract bleeding, heart dysfunction) have important significance for the prognosis of the enrolled patients with COVID-19. Herein, we report the discovery of the effects of hypoproteinemia and hematological diseases on the prognosis of COVID-19. Meanwhile, the scoring system established here can effectively evaluate objective scores for the early prognoses of patients with COVID-19 and can divide them into high- and low-risk groups (using a scoring threshold of 117.77, a score below which is considered low risk). The efficacy of the system was better than that of clinical classification using the current COVID-19 guidelines (C indexes, 0.95 vs. 0.89). Conclusions Age, clinical typing, sex, pulmonary insufficiency, hypoproteinemia, and four other factors were important for COVID-19 survival. Compared with general statistical methods, this method can quickly and accurately screen out the relevant factors affecting prognosis, provide an order of importance, and establish a scoring system based on the nomogram model, which is of great clinical significance. © Wolters Kluwer Health, Inc. All rights reserved.

The risk interdependence of cryptocurrencies: Before and during the COVID-19 pandemic

In this paper, we measure the risk interdependence of 12 major cryptocurrencies before and during the COVID-19 pandemic, based on a GARCH-Copula-VaR approach and a dynamic network analysis. We find that cryptocurrencies generally show high levels of volatility, speculation, homogeneity and tail risk contagion. Furthermore, the COVID-19 pandemic has a continuous impact on the cryptocurrency market. When financial institutions are increasingly investing in crypto assets, the hidden risks in the cryptocurrency market remain high. Therefore, this paper calls for attention on the cryptocurrency market from both investors and regulators.

Analysis of applicable pattern and mechanism of medicine and food homologous traditional Chinese medicine in prevention and treatment of modern viral infectious diseases

Objective To explore the application pattern and mechanism of medicine and food homologous traditional Chinese medicine (TCM) against modern viral diseases. Methods The method of literature mining was applied based on the characteristics of modern viral diseases, combining with ancient books and modern prescriptions for the prevention and treatment of viral diseases to build a relevant prescription database. Then SPSS and R language were used to analyze the high-frequency medicine and food homologous TCM and high confidence medicine and food homologous prescriptions in these prescriptions, and cluster analysis was carried out. The antiviral characteristic active ingredients of high-frequency medicinal and food homologous TCN were identified and analyzed, and the action mechanism of active ingredients against modern viral diseases was evaluate by network pharmacology. Results In the prevention and treatment of modern viral diseases, Gancao (Glycyrrhizae Radix et Rhizoma)-Chenpi (Citri Reticulatae Pericarpium)-Fuling (Poria) had the highest confidence, Glycyrrhizae Radix et Rhizoma-Jiegeng (Platycodonis Radix) had the highest support. At the same time, the prescriptions were clustered and analyzed to obtain Jinyinhua (Lonicerae Japonicae Flos)-Huangqi (Astragali Radix)-Huoxiang (Agastache rugosa), Glycyrrhizae Radix et Rhizoma-Xingren (Armeniacae Semen Amarum)-Poria-Platycodonis Radix-Citri Reticulatae Pericarpium, Ganjiang (Zingiberis Rhizoma)-Renshen (Ginseng Radix et Rhizoma), Zisu (Perilla frutescens)-Gegen (Puerariae Lobatae Radix), Lugen (Phragmitis Rhizoma)-Sangye (Mori Folium), Shengjiang (Zingiberis Rhizoma Recens)-Dazao (Jujubae Fructus) clustering new prescription. The core action targets of EGFR, CASP3, VEGFA, STAT3, MMP9, HSP90AA1, mTOR, PTGS2, MMP2, TLR4, MAPK14, etc were identified. The action mechanism involved human cytomegalovirus infection, coronavirus disease-coronavirus disease 2019 (COVID-19), etc. The core action pathway were phosphatidylinositol-3/kinase protein kinase B (PI3K/Akt) signal pathway, mitogen activated protein kinase (MAPK) signal pathway, interleukin-17 (IL-17) signal pathway, Janus kinase/signal transducer and activator of transcription (JAK/STAT) signal pathway, etc. Conclusion Through data mining, six new prescriptions for preventing and controlling modern viral diseases were obtained, and the mechanism of action was preliminarily discussed, which provided some reference for the research and development of medicine and food homologous TCM prescriptions for the prevention and treatment of viral epidemics and related health products.

Reversibility between 'cocreation' and 'codestruction': evidence from Chinese travel livestreaming

Travel livestreaming has brought light to the tourism industry during the darkness of the COVID-19 pandemic. Although travel livestreaming is in full swing in practice, academic research on this subject is somewhat lagging. Value dimensions/drivers derived from service field may contribute to the overall value of relevant stakeholders. The aim of this preliminary study is to identify emotional experiences from the perspective of travel livestream viewers, revealing the drivers of value cocreation and codestruction. Based on grounded theory, data were collected through in-depth semistructured interviews, and 11 functional dimensions were revealed, namely, authenticity and immersion, entertainment, remuneration, uniqueness, symmetry, utility and convenience, interactivity, technical support, livestreamer characteristics, and regulators. These dimensions are contributed by multiple entities, including travel suppliers, livestreamers, live platforms, other viewers, individuals, and the external environment. These findings provide evidence of the reversibility of cocreation and codestruction and makes contributions to both theory and practice, especially regarding implications for future research.

Negotiating interdisciplinary practice under the COVID-19 crisis: opportunities and challenges for tourism research

Purpose COVID-19 is currently the most serious crisis facing the world, and scholars in the medical and social sciences are working to save lives and mitigate the societal effects of the pandemic. This global public health emergency requires interdisciplinary work to provide comprehensive insight into a rapidly changing situation. However, attempts to integrate the medical and social sciences have met several barriers. This paper aims to identify feasible research opportunities for interdisciplinary studies across tourism and public health regarding COVID-19. Design/methodology/approach This paper presents a critical review of the literature and generates corresponding conceptual and theoretical frameworks to provide an in-depth discussion. Findings Tourism-related issues of destination management policies and capital are addressed from an interdisciplinary perspective. The conclusions encourage interdisciplinary research into global health problems, which will promote tourism's renaissance and sustainable development while enhancing social welfare. Practical implications This study focuses on integrating tourism and public health to offer stakeholders recommendations regarding destination management and tourism industry recovery amid COVID-19. Originality/value This paper represents a frontier study, critically uncovering a host of innovative interdisciplinary research directions and tourism-focused collaboration opportunities related to COVID-19.

Research progresses of nucleic acid based detection of pathogenic microorganisms

In December 2019, the global outbreak of Corona Virus Disease 2019 (COVID-19) made biosafety an attractive and crucial development direction globally. Rapid, accurate and low-cost detection of pathogenic microorganisms is one of the important issue to ensure biosafety, and is the key to epidemic prevention, control and diagnosis. This review elaborately introduces the applications of biosensors based on nucleic acid sequencing, isothermal amplification and gene editing (CRISPR/Cas) in integrated portable devices. The development of these technologies offers the possibility of developing “low-cost, high-efficiency and result-visualization” integrated detection methods. It is expected to provide technology guarantees for the effective prevention and control of pathogenic microorganisms. © 2021, Science in China Press. All rights reserved.

[Prevention and control of novel coronavirus infection in department of stomatology].

During a short period of time, the COVID-19, a respiratory disease caused by a novel coronavirus and first reported by the end of the year 2019 in China, has spread rapidly to many countries and regions outside China. The number of confirmed cases and deaths continued to rise. World Health Organization announced that the outbreaks of the novel coronavirus infection have constituted a Public Health Emergency of International Concern. Efficient infection control can prevent the virus from further spreading, which may make the pandemic situation under control. Due to the specialty of oral healthcare settings, the risk of cross infection is severe among patients and oral healthcare workers. It's urgent to implement more strict and efficient infection control protocols. This article, based on existing guidelines and published researches pertinent to dental infection-control principles and practices, mainly discusses epidemiological characteristics of COVID-19 and the features of nosocomial infection in oral healthcare settings, and furthermore provides recommendations on patient's evaluation, and infection control protocols in departments of stomatology under current circumstance.

[Exploration of omics mechanism and drug prediction of coronavirus-induced heart failure based on clinical bioinformatics].

Objective: Present study investigated the mechanism of heart failure associated with coronavirus infection and predicted potential effective therapeutic drugs against heart failure associated with coronavirus infection. Methods: Coronavirus and heart failure were searched in the Gene Expression Omnibus (GEO) and omics data were selected to meet experimental requirements. Differentially expressed genes were analyzed using the Limma package in R language to screen for differentially expressed genes. The two sets of differential genes were introduced into the R language cluster Profiler package for gene ontology (GO) and Kyoto gene and genome encyclopedia (KEGG) pathway enrichment analysis. Two sets of intersections were taken. A protein interaction network was constructed for all differentially expressed genes using STRING database and core genes were screened. Finally, the apparently accurate treatment prediction platform (EpiMed) independently developed by the team was used to predict the therapeutic drug. Results: The GSE59185 coronavirus data set was searched and screened in the GEO database, and divided into wt group, ΔE group, Δ3 group, Δ5 group according to different subtypes, and compared with control group. After the difference analysis, 191 up-regulated genes and 18 down-regulated genes were defined. The GEO126062 heart failure data set was retrieved and screened from the GEO database. A total of 495 differentially expressed genes were screened, of which 165 were up-regulated and 330 were down-regulated. Correlation analysis of differentially expressed genes between coronavirus and heart failure was performed. After cross processing, there were 20 GO entries, which were mainly enriched in virus response, virus defense response, type Ⅰ interferon response, γ interferon regulation, innate immune response regulation, negative regulation of virus life cycle, replication regulation of viral genome, etc. There were 5 KEGG pathways, mainly interacting with tumor necrosis factor (TNF) signaling pathway, interleukin (IL)-17 signaling pathway, cytokine and receptor interaction, Toll-like receptor signaling pathway, human giant cells viral infection related. All differentially expressed genes were introduced into the STRING online analysis website for protein interaction network analysis, and core genes such as signal transducer and activator of transcription 3, IL-10, IL17, TNF, interferon regulatory factor 9, 2'-5'-oligoadenylate synthetase 1, mitogen-activated protein kinase 3, radical s-adenosyl methionine domain containing 2, c-x-c motif chemokine ligand 10, caspase 3 and other genes were screened. The drugs predicted by EpiMed's apparent precision treatment prediction platform for disease-drug association analysis were mainly TNF-α inhibitors, resveratrol, ritonavir, paeony, retinoic acid, forsythia, and houttuynia cordata. Conclusions: The abnormal activation of multiple inflammatory pathways may be the cause of heart failure in patients after coronavirus infection. Resveratrol, ritonavir, retinoic acid, amaranth, forsythia, houttuynia may have therapeutic effects. Future basic and clinical research is warranted to validate present results and hypothesis.