Discovery of 3CLpro inhibitor of SARS-CoV-2 main protease.

Coronavirus main protease (3CLpro), a special cysteine protease in coronavirus family, is highly desirable in the life cycle of coronavirus. Here, molecular docking, ADMET pharmacokinetic profiles and molecular dynamics (MD) simulation were performed to develop specific 3CLpro inhibitor. The results showed that the 137 compounds originated from Chinese herbal have good binding affinity to 3CLpro. Among these, Cleomiscosin C, (+)-Norchelidonine, Protopine, Turkiyenine, Isochelidonine and Mallotucin A possessed prominent drug-likeness properties. Cleomiscosin C and Turkiyenine exhibited excellent pharmacokinetic profiles. Furthermore, the complex of Cleomiscosin C with SARS-CoV-2 main protease presented high stability. The findings in this work indicated that Cleomiscosin C is highly promising as a potential 3CLpro inhibitor, thus facilitating the development of effective drugs for COVID-19.

In this work, computer aided drug design technology was used to study the main protease 3CLpro of novel coronavirus, and functional small molecules with inhibitory effects on novel coronavirus were screened from the compound library of natural products. The results showed that Cleomiscosin C is highly promising as a potential 3CLpro inhibitor with prominent binding affinity, pharmacokinetic profiles and stability.

Impact of lockdown policies during the COVID-19 outbreak on a trauma center of a tertiary hospital in China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a major and costly public health emergency. AIM: To investigate the impact of China's lockdown policies during the COVID-19 outbreak on the level I trauma center of a tertiary comprehensive hospital of Traditional Chinese Medicine. METHODS: All patients admitted to our trauma center during a lockdown in 2020 and the same period in 2019 were enrolled. We collected data on demographics, daily visits, injury type, injury mechanism, injury severity score, and patient management for comparative analysis. RESULTS: The total number of patients in the trauma center of our hospital decreased by 50.38% during the COVID-19 Lockdown in 2020 compared to the same period in 2019. The average number of trauma visits per day in 2019 was 47.94, compared to 23.79 in 2020. Comparing the patients' demographic data, loss of employment was the most predominate characteristic in 2020 compared to 2019, while there was no significant difference in gender, age, and marital status between both periods. During the lockdown period, the proportion of traffic accident-related injuries, injuries due to falls greater than 1.5 m, and mechanical injuries decreased significantly, whereas the proportion of injuries caused by falls less than 1.5 m, cuts, assault, bites, and suicidal tendencies and other injuries increased relatively. In addition, the proportion of patients with minor injuries increased and serious injuries decreased during the lockdown. The hospitalization rate increased significantly, and there was no significant difference in emergency surgery and death rates. CONCLUSION: The lockdown policies during the COVID-19 outbreak significantly altered the number and mechanism of traumatic events in our hospital, which can be monitored regularly. Our results suggest that mandatory public health prevention and control measures by the government can reduce the incidence of traumatic events and the severity of traumatic injuries. Emergency surgery and mortality rates remain high, increased because of factors such as family injury and penetrating injury, and hospitalization rates have increased significantly. Therefore, our trauma center still needs to be fully staffed. Finally, from the perspective of the injury mechanism, indoor trauma is a major risk during a lockdown, and it is particularly important to develop prevention strategies for such trauma to reduce the medical burden of the next catastrophic epidemic.

An Agenda-Setting Account for Psychological Typhoon Eye Effect on Responses to the Outbreak of COVID-19 in Wuhan

During the outbreak of COVID-19 in Wuhan in 2020, we conducted a nationwide survey of 8170 respondents from 31 provinces/municipalities in China via Sojump to examine the relationship between the distance to respondents' city of residence from Wuhan and their safety concerns and risk perception of the epidemic that occurred in Wuhan City. We found that (1) the farther (psychologically or physically) people were from Wuhan, the more concerned they were with the safety of the epidemic risk in Wuhan, which we dubbed the psychological typhoon eye (PTE) effect on responses to the outbreak of COVID-19;(2) agenda setting can provide a principled account for such effect: the risk information proportion mediated the PTE effect. The theoretical and managerial implications for the PTE effect and public opinion disposal were discussed, and agenda setting was identified to be responsible for the preventable overestimated risk perception.

An Agenda-Setting Account for Psychological Typhoon Eye Effect on Responses to the Outbreak of COVID-19 in Wuhan.

During the outbreak of COVID-19 in Wuhan in 2020, we conducted a nationwide survey of 8170 respondents from 31 provinces/municipalities in China via Sojump to examine the relationship between the distance to respondents' city of residence from Wuhan and their safety concerns and risk perception of the epidemic that occurred in Wuhan City. We found that (1) the farther (psychologically or physically) people were from Wuhan, the more concerned they were with the safety of the epidemic risk in Wuhan, which we dubbed the psychological typhoon eye (PTE) effect on responses to the outbreak of COVID-19; (2) agenda setting can provide a principled account for such effect: the risk information proportion mediated the PTE effect. The theoretical and managerial implications for the PTE effect and public opinion disposal were discussed, and agenda setting was identified to be responsible for the preventable overestimated risk perception.

Correction: A Telehealth-Delivered Tai Chi Intervention (TaiChi4Joint) for Managing Aromatase Inhibitor-Induced Arthralgia in Patients With Breast Cancer During COVID-19: Longitudinal Pilot Study.

[This corrects the article DOI: 10.2196/34995.].

Cuff inflation technique is better than Magill forceps technique to facilitate nasotracheal intubation guiding by GlideScope® video laryngoscope.

Video laryngoscopy is often selected to assist nasotracheal intubation in allowing better laryngeal visualization, although there is no comparative study evaluating the effectiveness between auxiliary techniques by using Magill forceps and inflated cuff in GlideScope video laryngoscopy for nasotracheal intubation. Fifty-one of 100 patients in a Magill forceps group and 47 of 100 patients in a cuff inflation group were included in the final analysis in this randomized, single-blind, parallel, clinical trial study. Induction agents were routinely administered according to body weight, while intubation time spent, attempts, and related side effects were recorded. Compared to the Magill forceps group, the cuff inflation technique shortened the total intubation time (70.0 ± 24.5 s vs. 87.0 ± 25.0 s, p = 0.001) and the time of advancing the nasotracheal tube from oropharyngeal space into the trachea (25.9 ± 16.4 s vs. 42.3 ± 21.2 s, p < 0.001). However, the number of intubation attempts was not significantly different between groups. During tube advancement, the tube was rotated to accommodate the glottis and trachea more frequently in the cuff inflation group (p = 0.009), but the blade of the laryngoscope shifted and was adjusted to the proper position more frequently in the Magill forceps group (p < 0.001). In the Magill forceps group, the tube cuff might be clipped incidentally and the intubator might shift their gaze away from the screen during intubation, although there was no significant difference in intubation-related side effects between groups. Unlike the conventional approach, nasotracheal intubation with the GlideScope® video laryngoscope using the auxiliary technique of cuff inflation could be more suited than using Magill forceps.

Schaftoside inhibits 3CLpro and PLpro of SARS-CoV-2 virus and regulates immune response and inflammation of host cells for the treatment of COVID-19.

It is an urgent demand worldwide to control the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro) are key targets to discover SARS-CoV-2 inhibitors. After screening 12 Chinese herbal medicines and 125 compounds from licorice, we found that a popular natural product schaftoside inhibited 3CLpro and PLpro with IC50 values of 1.73 ± 0.22 and 3.91 ± 0.19 µmol/L, respectively, and inhibited SARS-CoV-2 virus in Vero E6 cells with EC50 of 11.83 ± 3.23 µmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of 3CLpro, and K157, E167 and A246 of PLpro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The anti-inflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.

A Telehealth-Delivered Tai Chi Intervention (TaiChi4Joint) for Managing Aromatase Inhibitor-Induced Arthralgia in Patients With Breast Cancer During COVID-19: Longitudinal Pilot Study.

BACKGROUND: Estrogen receptor-positive breast cancer is the most common type of breast cancer in postmenopausal women. Aromatase inhibitors (AIs) are the endocrine therapy of choice recommended for these patients. Up to 50% of those treated with an AI develop arthralgia, often resulting in poor adherence and decreased quality of life. OBJECTIVE: The study is a single-arm longitudinal pilot study aiming to evaluate the safety, feasibility, acceptability, and potential efficacy of TaiChi4Joint, a remotely delivered 12-week tai chi intervention designed to relieve AI-induced joint pain. METHODS: Women diagnosed with stage 0-III breast cancer who received an AI for at least 2 months and reported arthralgia with a ≥4 score on a 0 to 10 scale for joint pain were eligible for study enrollment. Participants were encouraged to join tai chi classes delivered over Zoom three times a week for 12 weeks. Program engagement strategies included using a private Facebook study group and a Box cloud for archiving live class recordings. The program uses SMS text messaging and emails with periodic positive quotes and evidence-based information on tai chi for facilitating community bonding and class attendance. Participants were invited to complete the following assessments at baseline and at 1-, 2-, and 3-month intervals from study enrollment: Brief Pain Inventory, Western Ontario and McMaster University Osteoarthritis Index (WOMAC), The Australian Canadian Osteoarthritis Hand Index (AUSCAN), Fatigue Symptom Inventory, Hot Flash Related Daily Interference Scale (HFRDIS), Pittsburgh Sleep Quality Index (PSQI), and Center for Epidemiological Studies-Depression (CES-D). RESULTS: A total of 55 eligible patients were invited to participate, and 39 (71%) consented and completed the baseline assessments. Participants attended 61% (median) of the suggested classes, with no tai chi-related adverse events reported. Of the 39 participants, 22 completed the 3-month follow-up assessment with a 56% retention rate. Study participants reported improvement from baseline compared to 3 months as follows (paired t test): Brief Pain Inventory (P<.001), AUSCAN pain subscale (P=.007), AUSCAN function subscale (P=.004), Fatigue Symptom Inventory (P=.004) and PSQI (P<.001), and HFRDIS (P=.02) and CES-D (P<.001). In particular, for our primary end point of interest, improvements in hip and knee symptoms, measured by WOMAC's three subscales, were clinically meaningful and statistically significant when adjusted for multiple comparisons from baseline to 3 months post intervention. CONCLUSIONS: The COVID-19 global pandemic has resulted in the need to rethink how mind-body therapies can be delivered. This study demonstrated the feasibility, acceptability, and potential efficacy of a telehealth-based tai chi intervention for reducing AI-induced arthralgia. The intervention decreased patient-reported pain and stiffness, and improved sleep quality and depressive symptoms. Fully powered, large, telehealth-based tai chi trials for AI-associated arthralgia are needed considering our promising findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04716920; https://www.clinicaltrials.gov/ct2/show/NCT04716920.

Bioactive prenylated phenolic compounds from the aerial parts of Glycyrrhiza uralensis.

In this work, a bioassay-guided fractionation strategy was used to isolate 26 phenolic compounds from the ethyl acetate partition of an ethanol extract of the aerial parts of Glycyrrhiza uralensis Fisch. ex DC. Among them, 8 prenylated phenolic compounds (glycyuralins Q-X) were described for the first time. The two enantiomers of glycyuralin Q were purified and their absolute configurations were established by ECD spectral calculations. (1″R, 2″S)-glycyuralin Q and (1″S, 2″R)-glycyuralin Q showed significant inhibitory activities against SARS-CoV-2 virus proteases 3CLpro with IC50 values of 1.5 ± 1.0 and 4.0 ± 0.3 µM, and PLpro with IC50 values of 2.4 ± 0.2 and 1.9 ± 0.1 µM, respectively. Four compounds showed potent cytotoxic activities against A549, Huh-7, and HepG2 human cancer cells with IC50 values ranging from 0.5 to 2.5 µM.

Long-term orientation and demographics predict the willingness to quarantine: A cross-national survey in the first round of COVID-19 lockdown.

To be or not to be quarantined? That is the question posed by COVID-19 pandemic to almost every resident in the world. Approximately three months after the first application of the COVID-19 lockdown to residents in 17 Asian, African, European, American, and Oceanian countries, we carried out a cross-national survey of 26,266 residents via online platforms such as Sojump and Prolific to investigate their willingness to quarantine and its influencing factors. Findings show that 1) The willingness to quarantine is low in countries with high long-term orientation; 2) Females are more willing to be quarantined than males; 3) Gender difference on willingness to quarantine is large among people with older age and low education. Theoretical and managerial implications are discussed. Understanding how culture and demographics affect people's willingness to quarantine not only provides insight into how to respond to the current pandemic, but also helps the world prepare for future crises.

AmAT19, an acetyltransferase from Astragalus membranaceus, catalyses specific 6α-OH acetylation for tetracyclic triterpenes and steroids.

Tetracyclic triterpenes and steroids are pharmacologically important molecules, and acetylation could improve their bioactivities. In this study, a highly regio- and stereo-specific acetyltransferase, AmAT19, was discovered from Astragalus membranaceus. AmAT19 could selectively catalyze the 6α-OH acetylation of four tetracyclic triterpenes and steroids. The strict selectivity is associated with different orientations of the 6α/ß-OH as indicated by molecular docking. Acetylated products 1a, 3a and 4a remarkably increased the inhibitory activity against the 3-chymotrypsin-like protease (3CLpro) of SARS-CoV-2, compared to 1, 3, and 4. AmAT19 could be a promising catalyst for specific 6α-OH acetylation to expand the molecular diversity of triterpenes and steroids.

Natural triterpenoids from licorice potently inhibit SARS-CoV-2 infection.

Introduction: The COVID-19 global epidemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a great public health emergency. Discovering antiviral drug candidates is urgent for the prevention and treatment of COVID-19. Objectives: This work aims to discover natural SARS-CoV-2 inhibitors from the traditional Chinese herbal medicine licorice. Methods: We screened 125 small molecules from Glycyrrhiza uralensis Fisch. (licorice, Gan-Cao) by virtual ligand screening targeting the receptor-binding domain (RBD) of SARS-CoV-2 spike protein. Potential hit compounds were further evaluated by ELISA, SPR, luciferase assay, antiviral assay and pharmacokinetic study. Results: The triterpenoids licorice-saponin A3 (A3) and glycyrrhetinic acid (GA) could potently inhibit SARS-CoV-2 infection, with EC50 of 75 nM and 3.17 µM, respectively. Moreover, we reveal that A3 mainly targets the nsp7 protein, and GA binds to the spike protein RBD of SARS-CoV-2. Conclusion: In this work, we found GA and A3 from licorice potently inhibit SARS-CoV-2 infection by affecting entry and replication of the virus. Our findings indicate that these triterpenoids may contribute to the clinical efficacy of licorice for COVID-19 and could be promising candidates for antiviral drug development.

Which Information Frame is Best for Reporting News on the COVID-19 Pandemic? An Online Questionnaire Study in China.

INTRODUCTION: The COVID-19 pandemic has received broad public attention and has been subject to social media discussion since the beginning of 2020. Previous research has demonstrated that framing could influence perception and behaviors of audience members in the mass media. The question addressed in this paper concerns which information frame is best for reporting negative news (eg, deaths) and positive news (eg, recoveries or cures) related to the outbreak of COVID-19. METHODS: During the Spring Festival holidays of 2020 in China, we investigated a sample of 8170 participants' risk perceptions and emotional responses to the pandemic, and their willingness to forward updates when the information is presented in different frames by using a 2 (domain: living [good news] vs dying [bad news]) × 2 (count: absolute vs relative) × 2 (population base: excluding population base vs including population base) × 2 (content: text-only vs text-plus-graphic) mixed factorial design, with the first factor being a within-subjects factor and the last three being between-subjects factors. RESULTS: Results indicated that (1) participants were more willing to forward good news (eg, cures) than bad news (eg, deaths); (2) when reporting bad news, the inclusion of the "population base" was effective in minimizing negative emotions; (3) when reporting good news, excluding the "population base" was more effective than including it in order to maximize positive emotions; (4) a text-plus-graphic frame worked better than a text-only frame in lowering the level of risk perception and negative emotions. DISCUSSION: This study is relevant to how individuals and organizations communicate information about this viral pandemic and the probable impact of this news on the general public.