An Integrated Strategy Designed to Explore the Common and Diverging Mechanisms of Potential Drugs against the Novel Coronavirus Pneumonia Based on Network Pharmacology and in Silico Molecular Docking Technology

Drug repositioning may be a promising way to find potential therapies against coronavirus disease 2019. Although chloroquine and hydroxychloroquine showed controversial results against the coronavirus disease 2019 disease, the potential common and diverging mechanisms of action are not reported and need to be dissected for better understanding them. An integrated strategy was proposed to systematically decipher the common and diverging aspects of mechanism of chloroquine and hydroxychloroquine against coronavirus disease 2019-disease network based on network pharmacology and in silico molecular docking. Potential targets of the two drugs and coronavirus disease 2019 related genes were collected from online public databases. Target function enrichment analysis, tissue enrichment maps and molecular docking analysis were carried out to facilitate the systematic understanding of common and diverging mechanisms of the two drugs. Our results showed that 51 chloroquine targets and 47 hydroxychloroquine targets were associated with coronavirus disease 2019. The core targets include tumor necrosis factor, glyceraldehyde 3-phosphate dehydrogenase, lymphocyte-specific protein-tyrosine kinase, beta-2 microglobulin, nuclear receptor coactivator 1, peroxisome proliferator-activated receptor gamma and glutathione disulfide reductase. Both chloroquine and hydroxychloroquine had good binding affinity towards tumor necrosis factor (affinity=-8.6 and -8.4 kcal/mol, respectively) and glyceraldehyde 3-phosphate dehydrogenase (-7.5 and -7.5 kcal/mol). Chloroquine and hydroxychloroquine both had good affinity with angiotensin-converting enzyme 2, 3-chymotrypsin-like protease and transmembrane serine protease 2. However, hydroxychloroquine manifested better binding affinity with the three proteins comparing with that of chloroquine. Chloroquine and hydroxychloroquine could have potential to inhibit over-activated immunity and inflammation. The potential tissue-specific regulation of the two drugs against severe acute respiratory syndrome coronavirus 2 infection may related with the lung, liver, brain, placenta, kidney, blood, eye, etc. In conclusion, our data systematically demonstrated chloroquine and hydroxychloroquine may have potential regulatory effects on coronavirus disease 2019 disease network, which may affect multiple organs, protein targets and pathways. Routine measurements of the chloroquine and hydroxychloroquine blood concentrations and tailored therapy regimen may be essential. But, further rigorous and high quality randomized controlled clinical trials are warranted to validate the antiviral effects of chloroquine and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2. Our proposed strategy could facilitate the drug repurposing efforts for coronavirus disease 2019 treatment.

Ecological Barrier Deterioration Driven by Human Activities Poses Fatal Threats to Public Health due to Emerging Infectious Diseases

The coronavirus disease 2019 (COVID-19) and concerns about several other pandemics in the 21st century have attracted extensive global attention. These emerging infectious diseases threaten global public health and raise urgent studies on unraveling the underlying mechanisms of their transmission from animals to humans. Although numerous works have intensively discussed the cross-species and endemic barriers to the occurrence and spread of emerging infectious diseases, both types of barriers play synergistic roles in wildlife habitats. Thus far, there is still a lack of a complete understanding of viral diffusion, migration, and transmission in ecosystems from a macro perspective. In this review, we conceptualize the ecological barrier that represents the combined effects of cross-species and endemic barriers for either the natural or intermediate hosts of viruses. We comprehensively discuss the key influential factors affecting the ecological barrier against viral transmission from virus hosts in their natural habitats into human society, including transmission routes, contact probability, contact frequency, and viral characteristics. Considering the significant impacts of human activities and global industrialization on the strength of the ecological barrier, ecological barrier deterioration driven by human activities is critically analyzed for potential mechanisms. Global climate change can trigger and expand the range of emerging infectious diseases, and human disturbances promote higher contact frequency and greater transmission possibility. In addition, globalization drives more transmission routes and produces new high-risk regions in city areas. This review aims to provide a new concept for and comprehensive evidence of the ecological barrier blocking the transmission and spread of emerging infectious diseases. It also offers new insights into potential strategies to protect the ecological barrier and reduce the wide-ranging risks of emerging infectious diseases to public health. (c) 2020 THE AUTHORS. Published by Elsevier LTD on behalf of Chinese Academy of Engineering and Higher Education Press Limited Company. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Moral Obligation, Fundraising Trust and Online Giving Sustainability: Evidence from China

The new information technology brings a new proposition to the practice and theoretical research of online giving. However, there is still a lack of empirical research for the specific causes and mechanism of individuals' participation in online giving, especially how to transform "one-time giving" into "continuous giving". Using the first-hand survey data in the crisis of Covid-2019, the paper finds that the crisis inspired the first online charity donation of college students, but the willingness of the individuals who participated in the online giving for the first time was significantly lower than those who have multiple online giving experience. What's more, there are significant differences in the key factors influencing the two groups of donors to make a continuous online charitable donation in the future. For the individuals who participated in an online giving for the first time, both moral obligation and fundraising trust had significant promoting effects. However, for individuals with multiple online giving experiences, the impact of moral obligation is not significant, and the most important factor is fundraising trust. Therefore, in the practice, improving the social reputation of the organizations and creating a good charity fundraising environment can effectively promote individual continuous online donation, which is an important basic strategy for NPOs to cultivate stable funding sources. Furthermore, when soliciting donations from the public who have participated in charitable donations many times, NPOs could emphasize the actual social benefits of the giving behavior and disseminate the process information of fundraising. However, for the charitable donors who are less involved or potential donors, NPOs should highlight the moral norms and social basic emotions.

Negative pressure drainage relieves respiratory discomfort for patients with medical face masks under ocular surgeries during COVID-19

AIM: To report our precaution practices for ocular surgeries under local anesthesia during COVID-19 outbreak and evaluate the respiration situation among the patients with medical face masks under ocular surgeries. METHODS: Sixty Chinese patients needed eye surgery treatment were recruited and given medical face masks as one of the COVID-19 precaution practices during eye surgery with local anesthesia. Oxygen supplementation and negative pressure drainage were applied to relieve the potential respiratory discomfort, and the respiratory comfort score was evaluated. RESULTS: Patients with medical face masks experienced mild to moderate respiratory discomfort with an overall mean score of 2.34±0.73. Supplementation of oxygen together with negative pressure drainage relieved this discomfort (overall mean score of 0.15±0.75;P<0.001). There is no gender and operation time difference on respiratory discomfort or discomfort relieve. Failure in negative pressure drainage led to severe respiratory discomfort. CONCLUSION: Negative pressure drainage could maintain the respiratory circulation in patients with medical face mask under eye surgery with local anesthesia. Application of medical face masks in patients under surgeries is recommended to protect the medical practitioners during the operations within COVID-19 outbreak. Copyright 2021 by the IJO Press.