High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (Mpro) and papain like protease (PLpro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851Mpro inhibitors and 205 PLpro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both Mpro and PLpro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of Mpro inhibitors and over 20% of PLpro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 Mpro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.

Dataset of international students' acceptance of online distance learning during COVID-19 pandemic: A preliminary investigation.

The dataset describes factors affecting international students' acceptance of Online Distance Learning (ODL) mode while pursuing oversea education during COVID-19 pandemic. The recruited respondents comprised of international students who were pursuing undergraduate degree programmes in the institutions of higher learning (IHLs) in Malaysia. Respondents were invited to participate in an online survey via Google Forms. A purposive sampling technique was adopted in this research whereby a total of 207 valid questionnaires were obtained and used for data analysis. Data outputs such as respondents' profile, Partial Least Squares Structural Equation Modelling, and importance-performance matrix analysis were presented. The data can be used as a reference source to identify areas of improvement by educators, academic management, and policy makers of IHLs.

Why Controlling the Asymptomatic Infection Is Important: A Modelling Study with Stability and Sensitivity Analysis

The large proportion of asymptomatic patients is the major cause leading to the COVID-19 pandemic which is still a significant threat to the whole world. A six-dimensional ODE system (SEIAQR epidemical model) is established to study the dynamics of COVID-19 spreading considering infection by exposed, infected, and asymptomatic cases. The basic reproduction number derived from the model is more comprehensive including the contribution from the exposed, infected, and asymptomatic patients. For this more complex six-dimensional ODE system, we investigate the global and local stability of disease-free equilibrium, as well as the endemic equilibrium, whereas most studies overlooked asymptomatic infection or some other virus transmission features. In the sensitivity analysis, the parameters related to the asymptomatic play a significant role not only in the basic reproduction number R0. It is also found that the asymptomatic infection greatly affected the endemic equilibrium. Either in completely eradicating the disease or achieving a more realistic goal to reduce the COVID-19 cases in an endemic equilibrium, the importance of controlling the asymptomatic infection should be emphasized. The three-dimensional phase diagrams demonstrate the convergence point of the COVID-19 spreading under different initial conditions. In particular, massive infections will occur as shown in the phase diagram quantitatively in the case R0>1. Moreover, two four-dimensional contour maps of Rt are given varying with different parameters, which can offer better intuitive instructions on the control of the pandemic by adjusting policy-related parameters.

Rapid Response in an Uncertain Environment: Study of COVID-19 Scientific Research Under the Parallel Model.

PURPOSE: The rapid response of COVID-19 scientific research played a significant role in pandemic prevention and control but failed to block the spread of the pandemic rapidly. Besides the complexity of the virus, the effectiveness of control and prevention measures, and other factors, the adaptation of the mode of conducting scientific research is also crucial for the prevention and control of COVID-19. In this study, a parallel model was used to explore the effects of the rapid scientific response on COVID-19 to assess why pandemics continue to spread under rapid response. ANALYSIS: This study presents the response of scientific research based on country/region and publication dimensions after analyzing COVID-19 studies in the Web of Science and PubMed databases. Co-occurrence analysis of items was used to determine the generation rate of COVID-19 research under different topics to identify the reflected innovation model. RESULTS: More manifestations on rapid response of COVID-19 research, especially compared with the linear model of SARS research, showed that the COVID-19 research followed a parallel or concurrent innovation model. CONCLUSION: Early multi-stakeholder partnership, convenient information sharing, and improved research competence promote the parallel model in COVID-19. Meanwhile, the uncertainty of the COVID-19 virus and the adverse effect of rapid response may limit the time efficiency of the parallel model. In conclusion, the rapid prevention and control of the pandemic cannot fully rely on scientific research but requires more combined effort under an uncertain global setting.

Structures of the Omicron spike trimer with ACE2 and an anti-Omicron antibody.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has become the dominant infective strain. We report the structures of the Omicron spike trimer on its own and in complex with angiotensin-converting enzyme 2 (ACE2) or an anti-Omicron antibody. Most Omicron mutations are located on the surface of the spike protein and change binding epitopes to many current antibodies. In the ACE2-binding site, compensating mutations strengthen receptor binding domain (RBD) binding to ACE2. Both the RBD and the apo form of the Omicron spike trimer are thermodynamically unstable. An unusual RBD-RBD interaction in the ACE2-spike complex supports the open conformation and further reinforces ACE2 binding to the spike trimer. A broad-spectrum therapeutic antibody, JMB2002, which has completed a phase 1 clinical trial, maintains neutralizing activity against Omicron. JMB2002 binds to RBD differently from other characterized antibodies and inhibits ACE2 binding.

What is holding customers back? Assessing the moderating roles of personal and social norms on CSR’S routes to Airbnb repurchase intention in the COVID-19 era

Despite Airbnb's disruption of the hotel industry, the COVID-19 pandemic has brought peer-to-peer (P2P) accommodation markets to a standstill. During the pandemic, Airbnb elevated their engagement in corporate social responsibility (CSR) in the quest to regain trust and develop an attractive brand identity. However, the effectiveness of CSR in engendering favorable behavioral outcomes in times of crisis remains inconclusive. Drawing upon the theoretical lens of the stakeholder theory, the norm activation model, and the theory of planned behavior, this study proposes a conceptual model to test the influence of Airbnb's CSR on repurchase/rebook intention through the mediation of customer trust and customer identification with the company (C-C identification). This study also examines the moderating effects of personal and social norms on the CSR–repurchase intention routes. Findings yielded by a survey of 528 Airbnb users in the US show that the strategic philanthropy component carries the most weight in determining customers' assessments of CSR. This is followed by the environmental, economic, and ethical components. Perceived CSR does not affect repurchase intention directly but does so indirectly through the mediation of C-C identification. Personal norms weaken the effects of perceived CSR and customer trust on repurchase intention. Theoretical and practical implications are provided.

Coevolution of COVID-19 research and China's policies.

BACKGROUND: In the era of evidence-based policy-making (EBPM), scientific outputs and public policy should engage with each other in a more interactive and coherent way. Notably, this is becoming increasingly critical in preparing for public health emergencies. METHODS: To explore the coevolution dynamics between science and policy (SAP), this study explored the changes in, and development of, COVID-19 research in the early period of the COVID-19 outbreak in China, from 30 December 2019 to 26 June 2020. In this study, VOSviewer was adopted to calculate the link strength of items extracted from scientific publications, and machine learning clustering analysis of scientific publications was carried out to explore dynamic trends in scientific research. Trends in relevant policies that corresponded to changing trends in scientific research were then traced. RESULTS: The study observes a salient change in research content as follows: an earlier focus on "children and pregnant patients", "common symptoms", "nucleic acid test", and "non-Chinese medicine" was gradually replaced with a focus on "aged patients", "pregnant patients", "severe symptoms and asymptomatic infection", "antibody assay", and "Chinese medicine". "Mental health" is persistent throughout China's COVID-19 research. Further, our research reveals a correlation between the evolution of COVID-19 policies and the dynamic development of COVID-19 research. The average issuance time of relevant COVID-19 policies in China is 8.36 days after the launching of related research. CONCLUSIONS: In the early stage of the outbreak in China, the formulation of research-driven-COVID-19 policies and related scientific research followed a similar dynamic trend, which is clearly a manifestation of a coevolution model (CEM). The results of this study apply more broadly to the formulation of policies during public health emergencies, and provide the foundation for future EBPM research.

SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target.

Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.

Discovery of SARS-CoV-2-E channel inhibitors as antiviral candidates.

Lack of efficiency has been a major problem shared by all currently developed anti-SARS-CoV-2 therapies. Our previous study shows that SARS-CoV-2 structural envelope (2-E) protein forms a type of cation channel, and heterogeneously expression of 2-E channels causes host cell death. In this study we developed a cell-based high throughput screening (HTS) assay and used it to discover inhibitors against 2-E channels. Among 4376 compounds tested, 34 hits with cell protection activity were found. Followed by an anti-viral analysis, 15 compounds which could inhibit SARS-CoV-2 replication were identified. In electrophysiological experiments, three representatives showing inhibitory effect on 2-E channels were chosen for further characterization. Among them, proanthocyanidins directly bound to 2-E channel with binding affinity (KD) of 22.14 µM in surface plasmon resonance assay. Molecular modeling and docking analysis revealed that proanthocyanidins inserted into the pore of 2-E N-terminal vestibule acting as a channel blocker. Consistently, mutations of Glu 8 and Asn 15, two residues lining the proposed binding pocket, abolished the inhibitory effects of proanthocyanidins. The natural product proanthocyanidins are widely used as cosmetic, suggesting a potential of proanthocyanidins as disinfectant for external use. This study further demonstrates that 2-E channel is an effective antiviral drug target and provides a potential antiviral candidate against SARS-CoV-2.

[A Case Report of Checkpoint Inhibitor Pneumonitis Caused by PD-1
Antibody-Safety and Effectiveness of Pirfenidone].

BACKGROUND: Immune checkpoint inhibitor associated pneumonia (CIP) is a serious side effect of immune checkpoint inhibitors. There is a consensus on the treatment of acute phase of CIP, but the treatment of pulmonary interstitial fibrosis after the acute phase is still a clinical problem to be solved. METHODS: The diagnosis and treatment of a non-small cell lung cancer (NSCLC) patient with immune checkpoint inhibitor associated pneumonia in the Stereotactic Radiotherapy Department of Qingdao Central Hospital were retrospectively analyzed, and literatures were reviewed. RESULTS: A 70-year-old male patient was diagnosed with Poorly differentiated squamous cell carcinoma of left lung with mediastinal lymph node metastasis T3N3M0 stage IIIc, EGFR/ALK/ROS1/RAF negative, PD-L1 (22c3) immunohistochemistry negative. After the progression of first-line chemotherapy, the patient was diagnosed as immune checkpoint inhibitor associated pneumonia grade 3 during second-line monotherapy with Nivolumab. After initial high-dose glucocorticoid pulse therapy, the lung computed tomography (CT) imaging and clinical symptoms of the patients were partially relieved, and then pirfenidone (300 mg tid) was given orally for more than 11 months. During the treatment of pirfenidone, the CT imaging and clinical symptoms of the patients were significantly improved, and there were no other adverse reactions except grade 1 nausea. During this period, chemotherapy and Anlotinib was given concurrently with pirfenidone and showed good safety profile. CONCLUSIONS: This case report is the first report of pirfenidone in the treatment of CIP, which provides a new idea for the clinical practice and research of CIP treatment.

A silver lining in the COVID-19 cloud: examining customers’ value perceptions, willingness to use and pay more for robotic restaurants

The COVID-19 pandemic has severely affected the restaurant industry due to enforced closures and limitations on social gatherings, prompting restaurateurs to innovate and adapt in order to ensure the viability of their businesses. Pandemic has also induced changes in our perceptions of safety in public spaces, necessitating the adoption of social distancing and more widespread use of online platforms for purchasing and communication. While the pandemic might be a catalyst for the adoption of contactless technologies, some restaurateurs remain hesitant to invest in service robots because they are not convinced of the return on investment and the potential value service robots can deliver to their customers. Therefore, this study aims to explore customer value perceptions of service robots and their impact on customers’ attitudes and behaviors toward robotic restaurants. Findings yielded by a survey of 445 potential diners in Taiwan show that customers’ willingness to use and to pay more for robotic restaurants are determined by their attitudes toward robots, which are influenced by functional, conditional, epistemic, emotional, co-creation, and social values. Our survey results also reveal that the importance of conditional value is amplified by crisis-specific antecedents, namely the need for physical distancing and mysophobia. These findings have implications for restaurant pricing policies and can be considered by restaurant managers when formulating strategies aimed at sustaining their business in these challenging times. (English) [ABSTRACT FROM AUTHOR] 由于强制关闭和限制社交聚会，COVID-19大流行严重影响了餐饮业，促使餐馆经营者进行创新和调整，以确保其业务的生存能力. 流感大流行还导致我们对公共场所安全的看法发生了变化，这就需要采用社交距离，并更广泛地使用在线购物和交流平台. 虽然这种流行病可能是采用非接触式技术的催化剂，但一些餐馆老板仍然对投资服务机器人犹豫不决，因为他们不相信服务机器人能给顾客带来的投资回报和潜在价值. 因此，本研究旨在探讨顾客对服务机器人的价值认知及其对顾客对机器人餐厅态度与行为的影响. 对台湾445位潜在食客的调查结果显示，顾客对机器人餐厅的态度决定了他们对机器人餐厅的使用意愿和支付意愿，这些态度受到功能、条件、认知、情感、共同创造和社会价值观的影响. 我们的调查结果还显示，条件价值的重要性被特定危机的前因放大，即需要身体距离和神秘恐惧症. 这些发现对餐厅定价政策有一定的启示，可供餐厅经理在制定策略时加以考虑，以期在这个充满挑战的时代维持其业务. (Chinese) [ABSTRACT FROM AUTHOR] Copyright of Journal of Hospitality Marketing & Management is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Public Awareness and Mask Usage during the COVID-19 Epidemic: A Survey by China CDC New Media.

An online survey conducted March 18-19, 2020 on the official China CDC WeChat account platform was used to evaluate the effect of public education about masks usage during the new coronavirus disease 2019 (COVID-19) epidemic. Chinese nationals older than 18 were eligible for the survey. The survey collected 5,761 questionnaires from the 31 provinces, municipalities, and autonomous regions of mainland China. 99.7% and 97.2% of the respondents answered correctly that respiratory droplets and direct contact were the main transmission routes. 73.3% of the respondents considered COVID-19 to be 'serious' or 'very serious'. When going to the hospital, 96.9% (2,885/2,976 had gone to a hospital) used a mask during the COVID-19 epidemic, while 41.1% (2,367/5,761) did not use a mask before the epidemic. Among the respondents that used public transportation and went shopping, 99.6% and 99.4%, respectively, wore masks. Among respondents who returned to work, 75.5% wore a mask at the workplace, while 86.3% of those who have not returned to work will choose to use masks when they return to the workplace. The Chinese public is highly likely to use a mask during COVID-19 epidemic, and the mask usage changed greatly since the COVID-19 outbreak. Therefore, public education has played an important role during the COVID-19 epidemic.

Co-evolution of COVID-19 Research and China’s Policies (preprint)

The dynamics of research are a prism that reflects interactions between science, the societal environment, and government policies. Against the backdrop of the ongoing global COVID-19 pandemic, this study explored the changes in, and development of, COVID-19 research in the period from December 30, 2019 to April 27, 2020. The study observes a salient change in research content: an earlier focus on “all patients”, “common symptoms”, and “nucleic acid test” was gradually replaced by a focus on “children”, “pregnant patients”, “severe symptoms”, and a combination of “nucleic acid test” and “antibody assay”. Some topics such as “vaccine R&D”, “knowledge, attitude, and practice” (KAP), and “mental health” were persistent throughout the recent history of China’s COVID-19 research. This study also reveals a correlation between the evolution of COVID-19 policies and the dynamic development of COVID-19 research. In the early stage of the outbreak in China, the formulation of COVID-19 policies followed a rapidly-progressing co-evolutionary model (CEM). The results of this study apply more broadly to the formulation of policies in public health emergencies, especially in the early stages.

Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the etiological agent responsible for the global COVID-19 (coronavirus disease 2019) outbreak. The main protease of SARS-CoV-2, Mpro, is a key enzyme that plays a pivotal role in mediating viral replication and transcription. We designed and synthesized two lead compounds (11a and 11b) targeting Mpro Both exhibited excellent inhibitory activity and potent anti-SARS-CoV-2 infection activity. The x-ray crystal structures of SARS-CoV-2 Mpro in complex with 11a or 11b, both determined at a resolution of 1.5 angstroms, showed that the aldehyde groups of 11a and 11b are covalently bound to cysteine 145 of Mpro Both compounds showed good pharmacokinetic properties in vivo, and 11a also exhibited low toxicity, which suggests that these compounds are promising drug candidates.