Antiviral activity and mechanism of the antifungal drug, anidulafungin, suggesting its potential to promote treatment of viral diseases.

BACKGROUND: The severe fever with thrombocytopenia syndrome disease (SFTS), caused by the novel tick-borne SFTS virus (SFTSV), was listed among the top 10 priority infectious disease by World Health Organization due to the high fatality rate of 5-30% and the lack of effective antiviral drugs and vaccines and therefore raised the urgent need to develop effective anti-SFTSV drugs to improve disease treatment. METHODS: The antiviral drugs to inhibit SFTSV infection were identified by screening the library containing 1340 FDA-approved drugs using the SFTSV infection assays in vitro. The inhibitory effect on virus entry and the process of clathrin-mediated endocytosis under different drug doses was evaluated based on infection assays by qRT-PCR to determine intracellular viral copies, by Western blot to characterize viral protein expression in cells, and by immunofluorescence assays (IFAs) to determine virus infection efficiencies. The therapeutic effect was investigated in type I interferon receptor defective A129 mice in vivo with SFTSV infection, from which lesions and infection in tissues caused by SFTSV infection were assessed by H&E staining and immunohistochemical analysis. RESULTS: Six drugs were identified as exerting inhibitory effects against SFTSV infection, of which anidulafungin, an antifungal drug of the echinocandin family, has a strong inhibitory effect on SFTSV entry. It suppresses SFTSV internalization by impairing the late endosome maturation and decreasing virus fusion with the membrane. SFTSV-infected A129 mice had relieving symptoms, reduced tissue lesions, and improved disease outcomes following anidulafungin treatment. Moreover, anidulafungin exerts an antiviral effect in inhibiting the entry of other viruses including SARS-CoV-2, SFTSV-related Guertu virus and Heartland virus, Crimean-Congo hemorrhagic fever virus, Zika virus, and Herpes simplex virus 1. CONCLUSIONS: The results demonstrated that the antifungal drug, anidulafungin, could effectively inhibit virus infection by interfering with virus entry, suggesting it may be utilized for the clinical treatment of infectious viral diseases, in addition to its FDA-approved use as an antifungal. The findings also suggested to further evaluate the anti-viral effects of echinocandins and their clinical importance for patients with infection of viruses, which may promote therapeutic strategies as well as treatments and improve outcomes pertaining to various viral and fungal diseases.

Artesunate: A review of its therapeutic insights in respiratory diseases.

BACKGROUND: Artesunate, as a semi-synthetic artemisinin derivative of sesquiterpene lactone, is widely used in clinical antimalarial treatment due to its endoperoxide group. Recent studies have found that artesunate may have multiple pharmacological effects, indicating its significant therapeutic potential in multiple respiratory diseases. PURPOSE: This review aims to summarize proven and potential therapeutic effects of artesunate in common respiratory disorders. STUDY DESIGN: This review summarizes the pharmacological properties of artesunate and then interprets the function of artesunate in various respiratory diseases in detail, such as bronchial asthma, chronic obstructive pulmonary disease, lung injury, lung cancer, pulmonary fibrosis, coronavirus disease 2019, etc., on different target cells and receptors according to completed and ongoing in silico, in vitro, and in vivo studies (including clinical trials). METHODS: Literature was searched in electronic databases, including Pubmed, Web of Science and CNKI with the primary keywords of 'artesunate', 'pharmacology', 'pharmacokinetics', 'respiratory disorders', 'lung', 'pulmonary', and secondary search terms of 'Artemisia annua L.', 'artemisinin', 'asthma', 'chronic obstructive lung disease', 'lung injury', 'lung cancer', 'pulmonary fibrosis', 'COVID-19' and 'virus' in English and Chinese. All experiments were included. Reviews and irrelevant studies to the therapeutic effects of artesunate on respiratory diseases were excluded. Information was sort out according to study design, subject, intervention, and outcome. RESULTS: Artesunate is promising to treat multiple common respiratory disorders via various mechanisms, such as anti-inflammation, anti-oxidative stress, anti-hyperresponsiveness, anti-proliferation, airway remodeling reverse, induction of cell death, cell cycle arrest, etc. CONCLUSION: Artesunate has great potential to treat various respiratory diseases.

Psychological stress of university students in the hardest-hit areas at different stages of the COVID-19 epidemic.

BACKGROUND: The outbreak of COVID-19 has caused extremely many serious consequences for the country and the world. In fact, it has seriously affected people's mental health. The purpose of this study is to understand the psychological stress among college students in different stages of epidemics in hard-hit areas such as Hubei. Moreover, to highlight the factors that influencing, their psychological conditions with the emphasis of further corresponding suggestions. METHODS: This study includes self-designed questionnaires in order to assess and analyze the psychological state of over 17,000 college students during the outbreak period in January and home quarantine in February. The questionnaire contains three aspects and six dimensions: pressure responses: stress susceptibility (SS), stress adjustment (SA), risk cognition: cognition of danger (CD), cognition of illness (CI) and stress reactions: emotional responses (ER), somatic responses (SR). This survey was done by an online questionnaire (www.wjx.cn) to investigate the psychological stress information of college students, and analyzed the data by SPSS 22.0 for Windows. RESULTS: Regarding the stress susceptibility, participants were more likely stressed in February than in January. Regarding the stress adjustment, the number of participants requiring pressure regulation or release in the February survey was significantly lower than that the effective in the January survey. The mean of the cognition of danger reduced significantly in February than in January, in other words, participants were highly worried about the epidemic in January than in February. Regarding the cognition of illness, participants in January had a more pessimistic attitude towards the epidemic than those in February. The emotional responses of the participants in February were more severe than those in January, while the somatic responses reduced significantly in February compared with January. Furthermore, females have stronger stress reactions than males. However, the SR doesn't have significant differences between females and males. CONCLUSION: After two surveys in January and February, it was found that the psychological stress of college students in Hubei was significantly different at different stages of the epidemic, where the epidemic developed, the psychological stress of college students become more severe. The psychological stress of the college students in Hubei Province, as a severely affected area, should be paid more attention.

Dissecting the novel mechanism of reduning injection in treating Coronavirus Disease 2019 (COVID-19) based on network pharmacology and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Reduning injection (RDNI) is a patented Traditional Chinese medicine that contains three Chinese herbal medicines, respectively are the dry aboveground part of Artemisia annua L., the flower of Lonicera japonica Thunb., and the fruit Gardenia jasminoides J.Ellis. RDNI has been recommended for treating Coronavirus Disease 2019 (COVID-19) in the "New Coronavirus Pneumonia Diagnosis and Treatment Plan". AIM OF THE STUDY: To elucidate and verify the underlying mechanisms of RDNI for the treatment of COVID-19. METHODS: This study firstly performed anti-SARS-CoV-2 experiments in Vero E6 cells. Then, network pharmacology combined with molecular docking was adopted to explore the potential mechanisms of RDNI in the treatment for COVID-19. After that, western blot and a cytokine chip were used to validate the predictive results. RESULTS: We concluded that half toxic concentration of drug CC50 (dilution ratio) = 1:1280, CC50 = 2.031 mg crude drugs/mL (0.047 mg solid content/mL) and half effective concentration of drug (EC50) (diluted multiples) = 1:25140.3, EC50 = 103.420 µg crude drugs/mL (2.405 µg solid content/mL). We found that RDNI can mainly regulate targets like carbonic anhydrases (CAs), matrix metallopeptidases (MMPs) and pathways like PI3K/AKT, MAPK, Forkhead box O s and T cell receptor signaling pathways to reduce lung damage. We verified that RDNI could effectively inhibit the overexpression of MAPKs, PKC and p65 nuclear factor-κB. The injection could also affect cytokine levels, reduce inflammation and display antipyretic activity. CONCLUSION: RDNI can regulate ACE2, Mpro and PLP in COVID-19. The underlying mechanisms of RDNI in the treatment for COVID-19 may be related to the modulation of the cytokine levels and inflammation and its antipyretic activity by regulating the expression of MAPKs, PKC and p65 nuclear factor NF-κB.

Psychological Typhoon Eye Effect During the COVID-19 Outbreak.

Background: The COVID-19 outbreak in Wuhan, Hubei, has brought serious consequences to the lives and mental health of people and has induced psychological stress and affected behavior. Methods: This study used self-designed questionnaires and SPSS to analyze the psychological and behavioral responses of people in different regions during the COVID-19 pandemic and to check for the presence of "psychological typhoon eye" (PTE) effects. The questionnaires adopted three measurement subscales, namely, the risk cognitive subscale, stress response subscale, and behavioral response subscale, and these were administered online (www.wjx.cn) to investigate the psychological and behavioral conduct of respondents from three areas that have been affected by COVID-19 to varying degrees. Exploratory factor analysis and principal component analysis were conducted to explore the factorial structure of these subscales, and confirmatory factor analysis was conducted to explore the structural validity of the questionnaires. The analysis results were used to build a revised 18-item questionnaire which validity was evaluated via ANOVA and LSD. Results: Results confirm the presence of PTE in the research areas during the onset of the COVID-19 outbreak and highlight some significant differences in the cognition and emotions of the residents in these areas. PTE affected the cognition, emotions, and cognitive and emotional responses of the respondents but did not affect their behavioral responses. Conclusion: The findings underscore the urgency of providing sustainable mental health care services across different areas during the COVID-19 outbreak. The residents of those areas worst hit by the pandemic, who may not have taken the situation seriously, require emotional guidance the most. Meanwhile, the residents of other areas, who showed the most negative psychological reactions to the pandemic, require a sense of security, a timely "disconnection" from negative information, an accurate cognition of stress, and an acceptance of self-responses.

Emotional "inflection point" in public health emergencies with the 2019 new coronavirus pneumonia (NCP) in China.

BACKGROUND: The outbreak of the new coronavirus pneumonia (NCP) in Wuhan, Hubei, has caused very serious consequences and severely affected people's lives and mental health. The outbreak will cause bad emotions such as tension, anxiety, fear, and so on. College students who have returned home from school face infection, isolation, and delay in starting school, and thus, their emotional stress should be observed. METHODS: This study used self-designed questionnaires and artificial intelligence (AI) to assess and analyze the emotional state of over 30,000 college students during the outbreak period in January (T1) and home quarantine in February (T2). This survey used online questionnaire (www.wjx.cn) to investigate the emotion information of college students. RESULTS: In the T1 survey, the "Typhoon Eye Effect" appeared. College students in Hubei are calmer than those outside Hubei in T1. However, in T2, an emotional "infection point" appeared, there was an "Exposure Effect", the negative emotions of students in Hubei largely increased and became higher than students outside Hubei. CONCLUSION: This survey found that there is an emotional "infection point" in February among college students, especially in the Hubei area. College students in Hubei are calmer than those outside Hubei in T1. In contrast, college students in Hubei were more nervous and scared than those outside Hubei in T2. This epidemic has caused the students to experience significant pressure and negative emotions. Therefore, universities and society should pay attention to their emotional adjustment, there are some suggestions such as establish the mental health organizations, test students' emotion status regularly.

Psychological stress of medical staffs during outbreak of COVID-19 and adjustment strategy.

COVID-19 has a significant impact on public health and poses a challenge to medical staffs, especially to front-line medical staffs who are exposed to and in direct contact with patients. To understand the psychological stress status of medical staffs during the outbreak of COVID-19, random sample questionnaire survey was conducted among 2110 medical staffs and 2158 college students in all provinces of China through a questionnaire, which was compiled and completed through the Questionnaire Star platform relying on Wechat, QQ, and other social software. The differences in psychological stress status of different groups were compared through the analysis of the questionnaire. Results revealed that in all provinces of China, medical staffs scored significantly higher on all items of psychological stress than college students (P < .001). In Wuhan, medical staffs scored significantly higher than college students in all items of psychological stress (P < .001). While among medical staffs, the group in Wuhan area scored significantly higher than the group outside Wuhan on the following items: "Thought of being in danger," "The possibility of self-illness," "Worrying about family infection" (P < .05), "Poor sleep quality," "Needing psychological guidance," and "Worrying about being infected" (P < .01) in the Psychological Stress Questionnaire, but on the item "Confidence in the victory of the epidemic," the group in Wuhan area scored significantly lower than the group outside Wuhan (P < .05). The emotion, cognition, physical, and mental response of front-line medical staff showed obvious "exposure effect", which calls for a psychological crisis intervention strategy that can be helpful.