Peimine inhibits variants of SARS‐CoV‐2 cell entry via blocking the interaction between viral spike protein and ACE2

Coronavirus disease 2019 (COVID‐19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Several vaccines against SARS‐CoV‐2 have been approved;however, variants of concern (VOCs) can evade vaccine protection. Therefore, developing small compound drugs that directly block the interaction between the viral spike glycoprotein and ACE2 is urgently needed to provide a complementary or alternative treatment for COVID‐19 patients. We developed a viral infection assay to screen a library of approximately 126 small molecules and showed that peimine inhibits VOCs viral infections. In addition, a fluorescence resonance energy transfer (FRET) assay showed that peimine suppresses the interaction of spike and ACE2. Molecular docking analysis revealed that peimine exhibits a higher binding affinity for variant spike proteins and is able to form hydrogen bonds with N501Y in the spike protein. These results suggest that peimine, a compound isolated from Fritillaria, may be a potent inhibitor of SARS‐CoV‐2 variant infection. PRACTICAL APPLICATIONS: In this study, we identified a naturally derived compound of peimine, a major bioactive alkaloid extracted from Fritillaria, that could inhibit SARS‐CoV‐2 variants of concern (VOCs) viral infection in 293T/ACE2 and Calu‐3 lung cells. In addition, peimine blocks viral entry through interruption of spike and ACE2 interaction. Moreover, molecular docking analysis demonstrates that peimine has a higher binding affinity on N501Y in the spike protein. Furthermore, we found that Fritillaria significantly inhibits SARS‐CoV‐2 viral infection. These results suggested that peimine and Fritillaria could be a potential functional drug and food for COVID‐19 patients.

Multiple Perspectives with Online EFL Practicum Technology Learning: Case Study on a Cloud.

This yearlong study describes multiple stakeholders' perspectives of 20 preservice English as Foreign Language (EFL) teachers, 43 elementary school students, 2 online mentors, and a teacher-researcher during a technology professional development practicum on a cloud. The case study provides qualitative and quantitative data from stakeholders concerning technology integration after participating in online project-based EFL instruction. The participating stakeholders encountered affordances and challenges that enhanced their online learning and teaching repertoires and offered nuanced evidence within this online professional development community. The findings call for continuing exploration of online practicums in preservice (language) teacher education and further research documenting complexities of multiple stakeholders' technology professional development.

Peimine inhibits variants of SARS-CoV-2 cell entry via blocking the interaction between viral spike protein and ACE2.

Coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several vaccines against SARS-CoV-2 have been approved; however, variants of concern (VOCs) can evade vaccine protection. Therefore, developing small compound drugs that directly block the interaction between the viral spike glycoprotein and ACE2 is urgently needed to provide a complementary or alternative treatment for COVID-19 patients. We developed a viral infection assay to screen a library of approximately 126 small molecules and showed that peimine inhibits VOCs viral infections. In addition, a fluorescence resonance energy transfer (FRET) assay showed that peimine suppresses the interaction of spike and ACE2. Molecular docking analysis revealed that peimine exhibits a higher binding affinity for variant spike proteins and is able to form hydrogen bonds with N501Y in the spike protein. These results suggest that peimine, a compound isolated from Fritillaria, may be a potent inhibitor of SARS-CoV-2 variant infection. PRACTICAL APPLICATIONS: In this study, we identified a naturally derived compound of peimine, a major bioactive alkaloid extracted from Fritillaria, that could inhibit SARS-CoV-2 variants of concern (VOCs) viral infection in 293T/ACE2 and Calu-3 lung cells. In addition, peimine blocks viral entry through interruption of spike and ACE2 interaction. Moreover, molecular docking analysis demonstrates that peimine has a higher binding affinity on N501Y in the spike protein. Furthermore, we found that Fritillaria significantly inhibits SARS-CoV-2 viral infection. These results suggested that peimine and Fritillaria could be a potential functional drug and food for COVID-19 patients.

Impact of Personality Traits and Information Privacy Concern on E-Learning Environment Adoption during COVID-19 Pandemic: An Empirical Investigation

In response to the COVID-19 pandemic, teaching and learning processes have experienced significant changes. Higher education institutions in Taiwan employed crisis intervention measures to instantly implement unified learning methods such as online teaching and learning. However, students had no time to prepare. Thus, the study explored the relationship between personality traits and the belief in conspiracy theory as antecedents of students' concern for information privacy (CFIP) and the subsequent relationship between students' CFIP and behavioral intention to report their personal information to e-learning service providers concerning the adoption of the e-learning environment. This cross-sectional study employed a questionnaire to accumulate data from university students in Taiwan. A total of 285 valid responses were used for the final analysis. The research framework was evaluated by structural equation modeling (SEM). The results suggest the proposed model explains about 66.4% of the variance of behavioral intention (R2 = 0.664). The findings support that four personality traits-agreeableness, openness to experiences, conscientiousness, and neuroticism-and belief in conspiracy theory significantly influenced students' CFIP. However, concerning extraversion, an insignificant path coefficient was reported. CFIP mediates the relationship between belief in conspiracy theory and behavioral intention. E-learning service providers should consider these determinants in improving and endorsing principles concerning e-learning environment adoption.

[Reflections on the Prospective Professional Competency of Taiwan Public Health Nurses].

Societal ageing, the rising prevalence of chronic diseases, and the COVID-19 pandemic have changed the global healthcare environment dramatically. These challenges have significantly burdened community medical and healthcare systems and complicated the work of public health nursing. As an important care provider on the frontlines of primary care, public health nurses (PHNs) must keep up with the current state of the medical environment and statistical data interpretation, scientific data translation, community resource sharing, and telehealth applications. These demands have greatly impacted the traditional routines and existing professional core competencies of PHNs. Discussions among 12 Taiwanese public healthcare experts and the definition of public health nursing capacity from World Health Organization were considered in this review. In addition to reflecting on social changes and the professional development of public health nursing, eight prospective recommendations were provided in this review to enhance the professional competence of PHNs and better prepare them for future changes in the health environment and primary healthcare. The suggestions provide a reference for updating the position statement of PHNs.

Interleukin-6 Test Strip Combined With a Spectrum-Based Optical Reader for Early Recognition of COVID-19 Patients With Risk of Respiratory Failure.

The COVID-19 pandemic has had a globally devastating impact. This highly contagious virus has significantly overburdened and undermined medical systems. While most infected patients experience only mild symptoms, those who are severely affect require urgent medical interventions and some develop acute respiratory failure and require mechanical ventilation. The broad and potentially deadly impact of infection underscores the critical need for early recognition, especially for those at risk for respiratory failure. Those who are severely impacted and at high risk for respiratory failure have been found to present high levels of serum cytokines, such as interleukin-6 (IL-6). Timely diagnosis and management of those at risk for respiratory failure is crucial. Measurement of IL-6 may provide a means for distinguishing such patients. Currently, most serum IL-6 detection relies on the use of laboratory-based conventional enzyme-linked immunosorbent assays. Although some rapid assays have been developed recently, they need to be conducted by specific technicians in central laboratory settings with advanced and expensive equipment. In this study, we propose an IL-6 test strip combined with a spectrum-based optical reader for early recognition of COVID-19-infected patients at imminent risk of acute respiratory failure requiring mechanical ventilator support. For our analyses, clinical demographic data and sera samples were obtained from three medical centers, and test strip specificity and detection performance were analyzed. This would help healthcare personnel stratify the risk of respiratory failure and provide prompt, and suitable management.

Tafenoquine and its derivatives as inhibitors for the severe acute respiratory syndrome coronavirus 2.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has severely affected human lives around the world as well as the global economy. Therefore, effective treatments against COVID-19 are urgently needed. Here, we screened a library containing Food and Drug Administration (FDA)-approved compounds to identify drugs that could target the SARS-CoV-2 main protease (Mpro), which is indispensable for viral protein maturation and regard as an important therapeutic target. We identified antimalarial drug tafenoquine (TFQ), which is approved for radical cure of Plasmodium vivax and malaria prophylaxis, as a top candidate to inhibit Mpro protease activity. The crystal structure of SARS-CoV-2 Mpro in complex with TFQ revealed that TFQ noncovalently bound to and reshaped the substrate-binding pocket of Mpro by altering the loop region (residues 139-144) near the catalytic Cys145, which could block the catalysis of its peptide substrates. We also found that TFQ inhibited human transmembrane protease serine 2 (TMPRSS2). Furthermore, one TFQ derivative, compound 7, showed a better therapeutic index than TFQ on TMPRSS2 and may therefore inhibit the infectibility of SARS-CoV-2, including that of several mutant variants. These results suggest new potential strategies to block infection of SARS-CoV-2 and rising variants.

Role of Infodemics on Social Media in the Development of People's Readiness to Follow COVID-19 Preventive Measures.

Unparalleled levels of misinformation have contributed to widespread misunderstandings about the nature of the coronavirus, its cure and preventative measures. Misinformation crosses borders rapidly with the help of social media, and this phenomenon is constantly increasing. Thus, the current study proposes a research framework to explore how citizens' trust in government and social media influences their readiness to follow COVID-19 preventive measures. Additionally, the role of a health infodemic was explored in perceptions and relationships among factors influencing an individual's readiness to follow COVID-19 preventive measures with data collected from 396 participants in Taiwan. The findings indicate citizens' trust in social media (TRSM), attitude (ATT), perceived benefit (PBT), personal innovativeness, and how peer referents positively influence their readiness. However, the relationship between citizens' trust in the government (TRGT) and their readiness to follow COVID-19 preventive measures (INT) is not statistically significant. The current study also explores the negative moderating effect of health infodemics on the relationship between TRSM and INT, TRGT and INT, ATT and INT, PBT and INT. Thus, the Taiwanese government must consider the current study's findings to develop attractively, informed, and evidence-based content, which helps its citizens improve their health literacy and counter the spread of misinformation.

Interpreting Usability Factors Predicting Sustainable Adoption of Cloud-Based E-Learning Environment during COVID-19 Pandemic

The COVID-19 pandemic affected educational institutions in an unrivaled way around the globe and forced them to switch from conventional classroom learning mode to e-learning mode within a short time period. Neither instructors nor students had ample time to prepare. The purpose of the current study is to accomplish two objectives: to explore the functional relationship between attitudinal readiness (ATR), subjective well-being (SWB), and cloud-based e-learning adoption intention in Taiwan and examine the constancy of recommended proposed relationships among different students’ groups. The model was then empirically tested using data of 256 university students by structural equation modeling. The current study demonstrates that ATR is completely explained through four dimensions: peer reference, perceived ease of use, perceived usefulness, and perceived ubiquity. SWB is positively interpreted through four dimensions: online course quality, system quality, perceived service quality, and perceived closeness. Self-efficacy has a significant relationship with both attitudinal readiness and adoption intention of a cloud-based e-learning system. Finally, the invariance test explores substantial variance among students who intend to use the system and students who reject it. Therefore, researchers and practitioners regarding educational, technological innovation must consider this empirical evidence to develop and validate a sustainable cloud-based e-learning program in higher education.

Tannic acid suppresses SARS-CoV-2 as a dual inhibitor of the viral main protease and the cellular TMPRSS2 protease.

The cell surface protein TMPRSS2 (transmembrane protease serine 2) is an androgen-responsive serine protease important for prostate cancer progression and therefore an attractive therapeutic target. Besides its role in tumor biology, TMPRSS2 is also a key player in cellular entry by the SARS-CoV viruses. The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has resulted in huge losses in socio-economy, culture, and human lives for which safe and effective cures are highly demanded. The main protease (Mpro/3CLpro) of SARS-CoV-2 is a critical enzyme for viral propagation in host cells and, like TMPRSS2, has been exploited for treatment of the infectious disease. Numerous natural compounds abundant in common fruits have been suggested with anti-coronavirus infection in the previous outbreaks of SARS-CoV. Here we show that screening of these compounds identified tannic acid a potent inhibitor of both SARS-CoV-2 Mpro and TMPRSS2. Molecular analysis demonstrated that tannic acid formed a thermodynamically stable complex with the two proteins at a KD of 1.1 mM for Mpro and 1.77 mM for TMPRSS2. Tannic acid inhibited the activities of the two proteases with an IC50 of 13.4 mM for Mpro and 2.31 mM for TMPRSS2. Mpro protein. Consistently, functional assays using the virus particles pseudotyped (Vpp) of SARS-CoV2-S demonstrated that tannic acid suppressed viral entry into cells. Thus, our results demonstrate that tannic acid has high potential of developing anti-COVID-19 therapeutics as a potent dual inhibitor of two independent enzymes essential for SARS-CoV-2 infection.

Pregnant women with COVID-19 and risk of adverse birth outcomes and maternal-fetal vertical transmission: a population-based cohort study in Wuhan, China.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. However, little is known about the association between pregnant women with COVID-19 and the risk of adverse birth outcomes. METHOD: We conducted a retrospective cohort study based on the Maternal and Child Health Information System (MCHIMS) of Wuhan, China. All pregnant women with singleton live birth recorded by the system between January 13 and March 18, 2020, were included. The adverse birth outcomes were preterm birth, low birth weight, neonatal asphyxia, premature rupture of membrane (PROM), and cesarean section delivery. Multivariate logistic regression was used to evaluate the associations between maternal COVID-19 diagnosis and adverse birth outcomes. RESULTS: Out of 11,078 pregnant women, 65 were confirmed with coronavirus disease 2019 (COVID-19). No deaths occurred from these confirmed cases or their newborns. Compared to pregnant women without COVID-19, pregnant women with a confirmed COVID-19 diagnosis had an increased risk of preterm birth (OR 3.34, 95% CI 1.60-7.00) and cesarean section (OR 3.63, 95% CI 1.95-6.76). There was no statistical difference in low birth weight, neonatal asphyxia, and PROM between the mothers with and without COVID-19. Among these newborns that were born to mothers with confirmed COVID-19, none was tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive or had abnormal CT results. Only one had diarrhea and three had a fever. CONCLUSIONS: This population-based cohort study suggests that COVID-19 during the later pregnancy is associated with an increased risk of adverse birth outcomes, including iatrogenic preterm birth and cesarean section delivery. Our data provide little evidence for maternal-fetal vertical transmission of SARS-CoV-2. It is important to monitor the long-term health effects of SARS-CoV-2 infection on pregnant women and their children.

Structural basis of SARS-CoV-2 main protease inhibition by a broad-spectrum anti-coronaviral drug.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or 2019 novel coronavirus (2019-nCoV), took tens of thousands of lives and caused tremendous economic losses. The main protease (Mpro) of SARS-CoV-2 is a potential target for treatment of COVID-19 due to its critical role in maturation of viral proteins and subsequent viral replication. Conceptually and technically, targeting therapy against Mpro is similar to target therapy to treat cancer. Previous studies show that GC376, a broad-spectrum dipeptidyl Mpro inhibitor, efficiently blocks the proliferation of many animal and human coronaviruses including SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), porcine epidemic diarrhea virus (PEDV), and feline infectious peritonitis virus (FIPV). Due to the conservation of structure and catalytic mechanism of coronavirus main protease, repurposition of GC376 against SARS-CoV-2 may be an effective way for the treatment of COVID-19 in humans. To validate this conjecture, the binding affinity and IC50 value of Mpro with GC376 was determined by isothermal titration calorimetry (ITC) and fluorescence resonance energy transfer (FRET) assay, respectively. The results showed that GC376 binds to SARS-CoV-2 Mpro tightly (KD = 1.6 µM) and efficiently inhibit its proteolytic activity (IC50 = 0.89 µM). We also elucidate the high-resolution structure of dimeric SARS-CoV-2 Mpro in complex with GC376. The cocrystal structure showed that GC376 and the catalytic Cys145 of Mpro covalently linked through forming a hemithioacetal group and releasing a sulfonic acid group. Because GC376 is already known as a broad-spectrum antiviral medication and successfully used in animal, it will be a suitable candidate for anti-COVID-19 treatment.

Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 main protease by tafenoquine in vitro (preprint)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the current pandemic, coronavirus disease 2019 (COVID-19), has taken a huge toll on human lives and the global economy. Therefore, effective treatments against this disease are urgently needed. Here, we established a fluorescence resonance energy transfer (FRET)-based high-throughput screening platform to screen compound libraries to identify drugs targeting the SARS-CoV-2 main protease (Mpro), in particular those which are FDA-approved, to be used immediately to treat patients with COVID-19. Mpro has been shown to be one of the most important drug targets among SARS-related coronaviruses as impairment of Mpro blocks processing of viral polyproteins which halts viral replication in host cells. Our findings indicate that the anti-malarial drug tafenoquine (TFQ) induces significant conformational change in SARS-CoV-2 Mpro and diminishes its protease activity. Specifically, TFQ reduces the alpha-helical content of Mpro, which converts it into an inactive form. Moreover, TFQ greatly inhibits SARS-CoV-2 infection in cell culture system. Hence, the current study provides a mechanistic insight into the mode of action of TFQ against SARS-CoV-2 Mpro. Moreover, the low clinical toxicity of TFQ and its strong antiviral activity against SARS-CoV-2 should warrant further testing in clinical trials.