ABSTRACT
Severe acute syndrome coronavirus 2(SARS-CoV-2) caused the global pandemic of COVID-19 since December 2019. Although most of COVID-19’s patients are mild or common, most of the severe patients have sepsis caused by the cytokine storm, which greatly increases the case fatality rate. Moreover, there is no effective drug that can resist the novel coronavirus so far, so it’s urgent to develop antiviral drug for the SARS-CoV-2. In our research, we screened 29 compounds with a score lower than -6 from 35 flavonoid compounds by molecular docking. (-)-Gallocatechin gallate, (+)-Gallocatechin and Baicalein were identified to have potent inhibit activity with IC50 5.774±0.805μM, 13.14±2.081μM and 5.158±0.928μM by FRET assay. Subsequently, we conducted molecular docking experiments, which showed that (-)-Gallocatechin gallate, (+)-Gallocatechin and Baicalein were non-covalently bound to Mpro through π-π stacking and hydrogen bonds in the Cys145 catalytic site. We further evaluated the effect of (-)-Gallocatechin gallate and Baicalein on cytokine storm use a mouse model of sepsis. (-)-Gallocatechin gallate and Baicalein significant reduced sepsis severity based on weight, murine sepsis score and survival rate and reduced the inflammatory factors level such as TNF-α, IL-1α, IL-4 and IL-10. Overall, (-)-Gallocatechin gallate and Baicalein may be potential drugs for symptomatic treatment of COVID-19.
Subject(s)
COVID-19ABSTRACT
BackgroundSo far, there has been no published population study on the relationship between COVID-19 infection and publics risk perception, information source, knowledge, attitude and four non-pharmaceutical interventions(NPI: hand washing, proper coughing habits, social distancing and mask wearing) during the COVID-19 outbreak in China. MethodsAn online survey of 8158 Chinese adults between 22 February to 5 March 2020 was conducted. Bivariate associations between categorical variables were examined using Fisher exact test. We also explored the determinants of four NPIs as well as their association with COVID-19 infection using logistic regression. ResultsOf 8158 adults included, 57 (0.73%) were infected with COVID-19. The overwhelming majority of respondents showed a positive attitude (99.2%), positive risk perception (99.9%) and high knowledge levels that were among the strongest predictors of four highly adopted NPIs (hand washing:96.8%; proper coughing: 93.1%; social distancing:87.1%; mask wearing:97.9%). There was an increased risk of COVID-19 infection for those who not washing hands (2.28% vs 0.65%; RR=3.53: 95%CI: 1.53-8.15; P<0.009); not practicing proper coughing (1.79% vs 0.73%; RR=2.44: 95%CI: 1.15-5.15;P=0.026); not practicing social distancing (1.52% vs 0.58%; RR=2.63:95%CI:1.48 - 4.67; P=0.002); and not wearing a mask (7.41% vs 0.6%; RR=12.38:95%CI:5.81-26.36; P<0.001). For those who did practice all other three NPIs, wearing mask was associated with significantly reduced risk of infection compared to those who did not wear a mask (0.6% vs 16.7%; p=0.035). Similarly, for those who did not practice all or part of the other three NPIs, wearing mask was also associated with significantly reduced risk of infection. In a penalised logistic regression model including all four NPIs, wearing a mask was the only significant predictor of COVID-19 infection among four NPIs (OR=7.20; 95%CI:2.24-23.11; p<0.001). ConclusionsWe found high levels of risk perception, positive attitude, desirable knowledge as well as a high level of adopting four NPIs. The relevant knowledge, risk perception and attitude were strong predictors of adapting the four NPIs. Mask wearing, among four personal NPIs, was the most effective protective measure against COVID-19 infection with added preventive effect among those who practised all or part of the other three NPIs.