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1.
Front Public Health ; 11: 1050759, 2023.
Article in English | MEDLINE | ID: covidwho-20245408

ABSTRACT

Objective: We aimed to investigate the influence of media on college students' mental health during the COVID-19 pandemic. Methods: After the COVID-19 outbreak, we used cross-sectional surveys through online questionnaires to investigate the mental health of college students in lockdown at home. We identified the influencing factors of PTSD symptoms using the Chi-Square test and ordinal logistic regression analysis. Results: In 10,989 valid questionnaires, 9,906 college students with no PTSD symptoms, 947 college students with subclinical PTSD symptoms (1-3 items), and 136 college students with four or more PTSD symptoms were screened out. The results showed that media content impacted the mental health of college students in lockdown at home. Positive media content was negatively correlated with PTSD symptoms among college students. PTSD symptoms were not associated with sources of information. Moreover, College students with PTSD symptoms would reduce their willingness to learn and could not complete online learning efficiently. Conclusion: PTSD symptoms are related to media exposure and excessive information involvement of COVID-19 in college students, which influences the willingness to attend online classes.


Subject(s)
COVID-19 , Pandemics , Humans , Cross-Sectional Studies , COVID-19/epidemiology , Communicable Disease Control , Disease Outbreaks , Students
2.
J Med Chem ; 66(4): 2744-2760, 2023 02 23.
Article in English | MEDLINE | ID: covidwho-2242001

ABSTRACT

Enveloped viruses depend on the host endoplasmic reticulum (ER) quality control (QC) machinery for proper glycoprotein folding. The endoplasmic reticulum quality control (ERQC) enzyme α-glucosidase I (α-GluI) is an attractive target for developing broad-spectrum antivirals. We synthesized 28 inhibitors designed to interact with all four subsites of the α-GluI active site. These inhibitors are derivatives of the iminosugars 1-deoxynojirimycin (1-DNJ) and valiolamine. Crystal structures of ER α-GluI bound to 25 1-DNJ and three valiolamine derivatives revealed the basis for inhibitory potency. We established the structure-activity relationship (SAR) and used the Site Identification by Ligand Competitive Saturation (SILCS) method to develop a model for predicting α-GluI inhibition. We screened the compounds against SARS-CoV-2 in vitro to identify those with greater antiviral activity than the benchmark α-glucosidase inhibitor UV-4. These host-targeting compounds are candidates for investigation in animal models of SARS-CoV-2 and for testing against other viruses that rely on ERQC for correct glycoprotein folding.


Subject(s)
1-Deoxynojirimycin , Antiviral Agents , COVID-19 , Glycoside Hydrolase Inhibitors , alpha-Glucosidases , Animals , 1-Deoxynojirimycin/chemistry , 1-Deoxynojirimycin/pharmacology , alpha-Glucosidases/drug effects , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Endoplasmic Reticulum/enzymology , Glycoproteins , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , SARS-CoV-2/metabolism , Quantitative Structure-Activity Relationship
3.
Proc Natl Acad Sci U S A ; 117(48): 30687-30698, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-922313

ABSTRACT

The SARS-CoV-2 pandemic has made it clear that we have a desperate need for antivirals. We present work that the mammalian SKI complex is a broad-spectrum, host-directed, antiviral drug target. Yeast suppressor screening was utilized to find a functional genetic interaction between proteins from influenza A virus (IAV) and Middle East respiratory syndrome coronavirus (MERS-CoV) with eukaryotic proteins that may be potential host factors involved in replication. This screening identified the SKI complex as a potential host factor for both viruses. In mammalian systems siRNA-mediated knockdown of SKI genes inhibited replication of IAV and MERS-CoV. In silico modeling and database screening identified a binding pocket on the SKI complex and compounds predicted to bind. Experimental assays of those compounds identified three chemical structures that were antiviral against IAV and MERS-CoV along with the filoviruses Ebola and Marburg and two further coronaviruses, SARS-CoV and SARS-CoV-2. The mechanism of antiviral activity is through inhibition of viral RNA production. This work defines the mammalian SKI complex as a broad-spectrum antiviral drug target and identifies lead compounds for further development.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus/drug effects , Filoviridae/drug effects , Host-Pathogen Interactions/drug effects , Multiprotein Complexes/metabolism , Orthomyxoviridae/drug effects , Cell Line , Genes, Suppressor , Models, Molecular , Molecular Targeted Therapy , Protein Binding , RNA, Small Interfering/metabolism , RNA, Viral/genetics , RNA, Viral/metabolism , Saccharomyces cerevisiae/genetics , Viral Proteins/metabolism , Virus Replication/drug effects
4.
Int J Infect Dis ; 93: 201-204, 2020 Apr.
Article in English | MEDLINE | ID: covidwho-1430

ABSTRACT

BACKGROUNDS: Up to February 16, 2020, 355 cases have been confirmed as having COVID-19 infection on the Diamond Princess cruise ship. It is of crucial importance to estimate the reproductive number (R0) of the novel virus in the early stage of outbreak and make a prediction of daily new cases on the ship. METHOD: We fitted the reported serial interval (mean and standard deviation) with a gamma distribution and applied "earlyR" package in R to estimate the R0 in the early stage of COVID-19 outbreak. We applied "projections" package in R to simulate the plausible cumulative epidemic trajectories and future daily incidence by fitting the data of existing daily incidence, a serial interval distribution, and the estimated R0 into a model based on the assumption that daily incidence obeys approximately Poisson distribution determined by daily infectiousness. RESULTS: The Maximum-Likelihood (ML) value of R0 was 2.28 for COVID-19 outbreak at the early stage on the ship. The median with 95% confidence interval (CI) of R0 values was 2.28 (2.06-2.52) estimated by the bootstrap resampling method. The probable number of new cases for the next ten days would gradually increase, and the estimated cumulative cases would reach 1514 (1384-1656) at the tenth day in the future. However, if R0 value was reduced by 25% and 50%, the estimated total number of cumulative cases would be reduced to 1081 (981-1177) and 758 (697-817), respectively. CONCLUSION: The median with 95% CI of R0 of COVID-19 was about 2.28 (2.06-2.52) during the early stage experienced on the Diamond Princess cruise ship. The future daily incidence and probable outbreak size is largely dependent on the change of R0. Unless strict infection management and control are taken, our findings indicate the potential of COVID-19 to cause greater outbreak on the ship.


Subject(s)
Coronavirus Infections/epidemiology , Disease Outbreaks/statistics & numerical data , Models, Biological , Pneumonia, Viral/epidemiology , Ships/statistics & numerical data , Betacoronavirus/physiology , COVID-19 , Computer Simulation , Coronavirus , Coronavirus Infections/virology , Humans , Incidence , Pandemics , Pneumonia, Viral/virology , Probability , SARS-CoV-2
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