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1.
researchsquare; 2024.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-4020649.v1

ABSTRACT

Background Breast surgery, emerging as an independent discipline with a wealth of specialist cases and an extensive case resource library in medical history. Contemporary clinical teaching faces challenges with traditional methods unable to address students' theoretical strength and practical limitations. The COVID-19 pandemic further strained learning environments, limiting students' exposure to patient diagnosis and treatment. Conventional clinical teaching, organized by disciplines, often results in technical isolation and a narrow clinical perspective, impeding the development of well-rounded medical professionals. Multidisciplinary Comprehensive Diagnosis and Treatment (MDT) emerges as a patient-centric, collaborative approach involving various medical departments in clinical decision-making. Despite its success in clinical settings, the effectiveness of MDT in undergraduate medical education remains largely unexplored.Methods This study conducted at the Breast Department of the First Affiliated Hospital of Zhengzhou University, aimed to compare the learning outcomes of clinical interns under traditional and MDT teaching modes. In a randomized controlled trial with 140 participants, the MDT group received comprehensive training from diverse healthcare professionals, while the traditional group had standard teaching. Evaluation included pre-test and post-test assessments on knowledge acquisition, skill acquisition, and clinical decision-making. Longitudinal analysis and statistical tests, including t-tests and multiple regression, were employed.Results A total of 140 clinical medicine students participated, randomly assigned to MDT (n = 70) and Traditional Teaching Mode (n = 70) groups. Key baseline characteristics, such as age, gender, and completion rates, were comparable between groups. For each group’s pre- and post-test scores, MDT group means consistently surpassed Traditional Teaching Mode, with significant differences (p < 0.05).Correlation analysis showed that there were no significant variable correlations between individual performance characteristics and test scores. Post-training, significant score improvements were observed in both groups across all tests (p < 2.2e-16). Utilizing the Wilcoxon rank sum test, pre-test differences were not significant. However, post-test scores favored the MDT group significantly (p = 0.0016, 2.8e-09, 3.6e-07). For students pursuing a master's, no statistically significant differences in specialty choice were observed between groups, though a trend towards more MDT students choosing surgical specialties was noted.Conclusion This study pioneers the application of the MDT teaching method in breast cancer clinical education, comparing its efficacy against traditional teaching modes. Findings demonstrate that MDT-based breast cancer diagnosis and treatment education is more efficient and optimized, offering a transformative basis for clinical undergraduate education reform in China. The results advocate for the reconfiguration of multidisciplinary consultation clinical teaching and traditional methods, promising enhanced educational outcomes and heightened medical student knowledge.

2.
Fermentation ; 8(12):678, 2022.
Article in English | MDPI | ID: covidwho-2123573

ABSTRACT

The aminoglycoside antibiotic neomycin has broad antibacterial properties and is widely used in medicine and agriculture. With the discovery of neomycin's potential applications in treating tumors and SARS-CoV-2, it is necessary to accelerate the biosynthesis of neomycin. In the present study, we investigated the effects of various inorganic salts on neomycin B (the main active neomycin) biosynthesis in Streptomyces fradiae SF-2. We found that 60 mM (NH4)2SO4 could promote neomycin B biosynthesis and cell growth most effectively. Further comparative transcriptomic analyses revealed that 60 mM (NH4)2SO4 inhibited the EMP and TCA cycles and enhanced the expression of neo genes involved in the neomycin B biosynthesis pathway. Finally, a neomycin B potency of 17,399 U/mL in shaking flasks was achieved by overexpressing neoE and adding 60 mM (NH4)2SO4, corresponding to a 51.2% increase compared with the control S. fradiae SF-2. In the present study, the mechanism by which (NH4)2SO4 affects neomycin biosynthesis was revealed through transcriptomics, providing a reference for the further metabolic engineering of S. fradiae SF-2 for neomycin B production.

3.
Chinese Journal of Virology ; 37(6):1292-1301, 2021.
Article in Chinese | GIM | ID: covidwho-2081015

ABSTRACT

Kashgar is a prefecture in Xinjiang Uygur Autonomous Region. China. Kashgar Prefecture (KP) is a land-cargo port connecting China with central Asian countries and Europe. Frequent transportation of cargo has increased the risk of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) introduction into China, which has increased the pressure on coronavirus disease-2019 (COVID-19) prevention and control. In November 2020, an imported virus-induced COVID-19 outbreak occurred in KP. To investigate the genetic characterization of SARS-CoV-2 that contaminated the trucks and containers, and the potential of border rapid logistics system to serve as carriers for SARS-CoV-2 transmission, thirty-five SARS-CoV-2-positive nucleic-acid samples collected from KP cross-border trucks and containers from 6-10 November 2020 were subjected into SARS-CoV-2 genomic sequencing and comparative analyses. The results showed that the median (minimum to maximum) Ct value of ORF1ab was 37.64 (28.91-39.81) . and that of the N gene was 36.50 (26.35-39.30), and the median (minimum to maximum) of the reads mapping ratio to SARS-CoV-2 was 51.95% (0.86%-99.31%), which indicated low viral loads in these environmental samples. Eighteen of 35 samples had genomic coverage >70%. According to the Pango nomenclature, 18 SARS-CoV-2 sequences belonged to six lineages (B.1, B.I.1, B.1.9. B.1.1.220, B.1.153 and B.1.465), three of which (B.I. B.1.1 and 8.1.153) were found in case samples from the same period of four China-neighboring countries. Analyses of nucleotide mutations and phylogenetic trees showed that the genome sequences of SARS-CoV-2 collected from the same location were similar. Four of 18 sequences were in a sub-lineage with the representative strain of COVID-19 outbreak in KP, one of which had 1 or 2 differences in nucleotide mutation sites with the strain that caused the COVID-19 outbreak in KP, which indicated high homology in the viral genome. We showed that cross-border trucks and containers were contaminated by various genotypes of SARS-CoV-2 from other countries during the outbreak in KP. and in which contained the parental virus of the KP cases. These trucks and containers served as carriers for SARS-CoV-2 introduction from other countries to cause local transmission. Our results provide important references for COVID-19 prevention-and-control strategies in border ports and tracing of outbreak sources in China.

4.
ssrn; 2021.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3932259

ABSTRACT

Background: The onset of various kidney diseases have been reported after COVID-19 vaccination. However, detailed clinical and pathological examination of kidney injury in patients receiving inactivated vaccines are lacking.Methods: We screened and analyzed patients with newly diagnosed kidney diseases after inactivated SARS-CoV-2 vaccination in Peking University First Hospital from January 2021 to August 2021. We obtained samples of blood, urine, and renal biopsy tissues. Clinical and laboratory information, as well as light microscopy, immunostaining and ultrastructural observation were described. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein and Nucleoprotein were stained using immune-fluorescence technique in the kidney biopsy samples. SARS-CoV-2 specific antibodies were tested using magnetic particle chemiluminescence immunoassay.Findings: The study group included 17 patients, including immune complex mediated kidney diseases (IgA nephropathy, membranous nephropathy and lupus nephritis), podocytopathy (minimal change disease and focal segmental glomerulosclerosis) and others (antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, anti-GBM nephritis, acute tubulointerstitial nephritis, and thrombotic microangiopathy). Seven patients (41.18%) developed renal disease after the first dose and 10 (58.82%) after the second dose. We found no definitive evidence of SARS-CoV-2 Spike protein or Nucleoprotein deposition in the kidney biopsy samples. Serological markers implicated abnormal immune responses in predisposed individuals. Treatment and follow-up (median = 86 days) showed that biopsy diagnosis informed treatment and prognosis in all patients.Interpretation: We observed various kidney diseases following inactivated SARS-CoV-2 vaccine administration. Our findings provide an evidence against direct vaccine protein deposition as the major pathomechanism, but implicate abnormal immune responses in predisposed individuals. These findings expand our understanding of inactivated SARS-CoV-2 vaccine renal safety.Funding: This study was funded by National Natural Science Foundation of China (91742205, 82170711, 81800636, 82070733, 81625004), Clinical Medicine Plus X—Young Scholars Project of Peking University (PKU2021LCXQ017), the Fundamental Research Funds for the Central Universities, CAMS Innovation Fund for Medical Sciences (2019-I2M-5-046), Yunnan Provincial Science and Technology Department (202102AA100051 and 202003AC100010, China), and Beijing Young Scientist Program (BJJWZYJH01201910001006).Declaration of Interest: The authors declare no competing interests.Ethical Approval: This study was approved by the institutional review board of Peking University First Hospital (2021-352) and the Committee on Human Subject Research and Ethics of Yunnan University (CHSRE2021020). Written Informed Consent Form was obtained from each participant.

5.
researchsquare; 2021.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-580679.v1

ABSTRACT

Background Patients with severe coronavirus disease 2019 (COVID-19) who develop acute kidney injury (AKI) in the intensive care unit (ICU) have extremely high rates of mortality. This study evaluated the prognostic impact of AKI duration on in-hospital mortality in elder patients.Methods We performed a retrospective study of 126 patients with confirmed COVID-19 with severe or critical disease who treated in the ICU from February 4, 2020, to April 16, 2020. AKI was defined according to the Kidney Disease Improving Global Outcomes serum creatinine (Scr) criteria. AKI patients were divided into transient AKI and persistent AKI groups based on whether Scr level returned to baseline within 48 h post-AKI.Results In total, 107 patients were included in the final analysis. The mean age was 70 (64–78) years, and 69 (64.5%) patients were men. AKI occurred in 48 (44.9%) during their ICU stay. Of these, 11 (22.9%) had transient AKI, 37 (77.9%) had persistent AKI. In-hospital mortality was 18.6% (n =11) for patients without AKI, 72.7% (n=8) for patients with transient AKI, and 86.5% (n=32) for patients with persistent AKI (P<0.001). Kaplan–Meier curve analysis revealed that patients with both transient AKI and persistent AKI had significantly higher death rates than those without AKI (log-rank P<0.001). Multivariate Cox regression analysis revealed that transient and persistent AKI were an important risk factor for in-hospital mortality in older patients with severe COVID-19 even after adjustment for variables (hazard ratio [HR]=2.582; 95% CI: 1.025–6.505; P=0.044; and HR=6.974; 95% CI: 3.334–14.588; P<0.001).Conclusions AKI duration is a useful parameter to predict of worse clinical outcomes in elder patients with COVID-19 in the ICU. Among AKI patients, those persistent AKI have a lower in-hospital survival rate than those transient AKI, emphasizing the importance of identifying an appropriate treatment window for early intervention.

7.
View ; 2(2):e115, 2021.
Article in English | Wiley | ID: covidwho-1176315

ABSTRACT

In article number 20200082, Yong Guo and co-workers have shown the detection of SARS-CoV-2 RNA by digital PCR.

8.
researchsquare; 2021.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-306368.v1

ABSTRACT

Objectives The purpose of this study is to describe the situation of the COVID-19 in European countries and identify important factors related to prevention and control.Methods We obtained data from World Health Statistics 2020 and the Institute for Health Metrics and Evaluation (IHME). We caculated the Rt values of 51countries in Europe under different prevention and control measures. We used lasso regression to screen factors associated with morbidity and mortality. For variables selected, we used quantile regression to analyze the relevant influencing factors in countries with different levels of morbidity or mortality.Results The government has a great influence on the change of Rt value through prevention and control measures. The most important factor for personal and group prevention and control is the mobility index, testing, the closure of educational facilities, restrictions on large-scale gatherings, and commercial restrictions. The number of ICU beds and doctors in medical resources are also key factors. Basic sanitation facilities, such as the proportion of safe drinking water, also have an impact on the COVID-19 epidemic.Conclusions This study describes the current status of COVID-19 in European countries. We found key factors in individual prevention and control measures and group prevention and control measures.

9.
researchsquare; 2021.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-164896.v1

ABSTRACT

Objectives: This study aimed to assess the influence of risk cognitive and characteristics of mobile phones using on sleep quality during the COVID-19 epidemic.Methods: We used the Pittsburgh Sleep Quality Index (PSQI), mobile phone use characteristics and a mobile phone use risk cognitive questionnaire, which was answered by 1207 college students. The data were statistically analyzed with SPSS 21.0 software.Results: There were significant differences in the general and poor sleep quality groups (p=0.013 and 0.037, respectively) between before and during the COVID-19 period. In the PSQI scores there were significant differences of the participants between before and during COVID-19 period with respect to dimensions other than sleep quality. Generalized linear regression analysis showed that the “pros and cons” (p=0.007) of mobile phone use for the items “How often do you take a break during use time?” (p=0.003), “Will subjectively increase the distance between the screen and the eyes?” (p=0.003), “Daily accumulated use time (hours)” (p=0.003) and “use time before bed with the lights off (hours)” (p<0.001) were significantly correlated with sleep quality.Conclusions: Risk cognitive and characteristics of mobile phone using influence sleep quality during the COVID-19 epidemic.

10.
ssrn; 2020.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3576929
11.
researchsquare; 2020.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-131069.v1

ABSTRACT

Background: To put COVID-19 patients into hospital timely, the clinical diagnosis had been implemented in Wuhan in the early outbreak. Here we compared the epidemiological characteristics of laboratory-confirmed and clinically diagnosed cases with COVID-19 in Wuhan.Methods: Demographics, case severity and outcomes of 29886 confirmed cases and 21960 clinically diagnosed cases reported between December 2019 and February 24, 2020, were compared. The risk factors were estimated, and the effective reproduction number of SARS-CoV-2 (Rt) was also calculated.Results: The interval between symptom onset and diagnosis of confirmed and clinically diagnosed cases reduced gradually as time went by, and the proportion of severe and critical cases as well as case fatality rates of the two groups all decreased over time. The proportion of severe and critical cases (21.5% vs 14.0%, P<0.0001) and case fatality rates (5.2% vs 1.2%, P<0.0001) of confirmed cases were all higher than those of clinically diagnosed cases. Risk factors for death we observed in all two groups were older age, male, severe or critical cases. Rt showed a downward trend after the lockdown of Wuhan, it dropped below 1.0 on February 6 among confirmed cases, and February 8 among clinically diagnosed cases.Conclusion: Public health responses taken in Wuhan, including clinical diagnosis, have contributed to slow transmission. In cases where testing kits are insufficient, clinical diagnosis is effective, which is helpful to quarantine or treat infected cases as soon as possible, and prevent the epidemic from worsening. To decrease the case fatality rate of COVID-19, it is necessary to strengthen early warning and intervention of severe and critical elderly men.

12.
ssrn; 2020.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3722066

ABSTRACT

Background: Although laboratory tests have become an indispensable part in clinical practice, its role in severity classification and death risk-stratification of coronavirus disease-2019 (COVID-19) remains unvalidated. Methods: In 3342 hospitalized patients with COVID-19, those of mild or moderate subtype were categorized into non-severe group, while those of severe or critical subtype categorized into severe group. Initial laboratory data were analyzed and compared according to disease severity and outcome. Diagnostic models for severe group were generated on risk factors identified by logistic regression and receiver operating characteristic (ROC) analyses. Cox regression and ROC analyses on risk factors were utilized to construct prognostic models. Findings: In identification of patients in severe group, while age, neutrophil-to-lymphocyte ratio, α-hydroxybutyrate dehydrogenase were identified as independent predictors, the value of combination of them appears modest (area under the curve; AUC = 0.694). Further ROC analyses indicated that among patients in severe group, laboratory indices had favorable value in identifying patients of critical subtype rather than severe subtype. For death outcome, IL-6, co-existing cerebrovascular disease, prothrombin time activity, and urea nitrogen were independent risk factors. An IL-6 single-parameter model was finalized for distinguishing between fatal and recovered individuals (AUC = 0.953). Finally, a modified death risk-stratification strategy based on clinical severity and IL-6 levels enables more identification of non-survivors in patients with non-critical disease. Interpretation: Laboratory screening provides a useful tool for COVID-19 management in identifying patients with critical condition and stratifying risk levels of death. Funding: National Nature Science Foundation of China (Grants 81702999 and 81971133).Declaration of Interests: None reported conflicts of interest.Ethics Approval Statement: Written informed consent was waived by the ethics committee of the designated hospitals for patients with emerging infectious diseases.

13.
International Journal of Environmental Research and Public Health ; 17(21):7974, 2020.
Article in English | MDPI | ID: covidwho-896424

ABSTRACT

This study explored the associations of individual factors (demographic characteristics, self-confidence in responding to the coronavirus disease 2019 (COVID-19), and self-rated physical and mental health) and environmental factors (perceived confidence in COVID-19 management by the regional government and adequacy of resources and support available to address the COVID-19 pandemic) with worry toward COVID-19 and general anxiety among people in Taiwan. The Chi-square was used to compare difference for worry and anxiety among categorical variables. The logistic regression was used to examine the associations between worry as well as anxiety and individual as well as environmental factors. In total, 1970 respondents were recruited and completed an online survey on worry regarding COVID-19, general anxiety during the pandemic, and individual and environmental factors. In total, 51.7% and 43.4% of respondents reported high levels of worry toward COVID-19 and general anxiety, respectively. Exhibited worse self-rated mental health, lower self-confidence in COVID-19 management, and insufficient mental health resources were significantly associated with high levels of both worry toward COVID-19 and general anxiety. Lower perceived confidence in COVID-19 management by the regional government was associated with a higher level of worry toward COVID-19. Lower perceived social support was associated with a higher level of general anxiety during the COVID-19 pandemic. The results showed that high levels of worry toward COVID-19 and general anxiety were prevalent during the outbreak. This suggests health care providers need additional surveillance of worry and anxiety during the pandemic. Multiple individual and environmental factors related to worry toward COVID-19 and general anxiety were identified. Factors found in the present study can be used for the development of intervention programs, supportive services, and government policy to reduce worry and anxiety during the COVID-19 pandemic

14.
medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.11.03.20224972

ABSTRACT

Background: The current increase in the spread of (SARS-CoV-2) critically needs a multitarget diagnostic assays to promote analytical sensitivity to facilitate the public health actions. Objective: The aim of this study was to develop a new primer-probe set targeting N gene of SARS-CoV-2 to improve the sensitivity for detection of COVID-19 Corona Virus Disease 2019 in multiplex rRT-PCR (Reversetranscript Realtime PCR) and ddPCR (Droplet Digital PCR). Results: We designed primers/probes set N(LZU3) targeting the N gene of 2019-nCov and proved its sensitivity in both rRT-PCR and ddPCR. When the quantity of template was 105 copies/reaction, the mean Ct value of N(LZU3) was 32.563, the detection rate was 91.7%. If the quantity of template was 52.5 copies/reaction, the mean Ct value of N(LZU3) was 33.835, and the detection rate was 83.3%, which were similar with that of N(CDC) and N(USA). The calculated lower limit of detection (LOD) of the new primer-probe set N(LZU3) used in rRT-PCR was 118 copies/reaction. We also did one-step ddPCR for detection the same serial dilution of RNA template. It shows good linearity for primer/probe sets N(LZU3). The calculated lower limit of detection (LOD) of N(LZU3) was 22.4 copies/reaction, which was 1.12 copies/ul. Conclusion: The novel primer-probe set(LZU3) targeting N gene of SARS-CoV-2 could be both used in rRT-PCR and ddPCR with better sensitivity, furthermore, ddPCR method had higer sensitivity than rRT-PCR, hence it could significantly improve SARS-CoV-2 detection efficiency in low virus load and asymptomatic infection.

15.
researchsquare; 2020.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-102042.v1

ABSTRACT

We study a new fractal model for prediction of contagions of CoViD-19 using experimental data from October 10, 2020 to predict contagions from November until February 2021 in Italy. We obtain that the time of the peak is estimated to be at November 11, 2020 when number of contagions will be about 38489 cases.

16.
researchsquare; 2020.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-98910.v1

ABSTRACT

We study a new fractal model for prediction of contagions of CoViD-19 (Sarbeco Betavirus SARS-CoV-2) from August 24, 2020 to July 31, 20201 in Apulia that is a region of Italy. We obtain that the time of the peak is estimated to be at December 7, 2020 and the number of contagions will be about 575 cases. 

17.
researchsquare; 2020.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-98615.v1

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a preliminary understanding of the replication and transcription mechanisms of SARS-CoV-2 has recently emerged, their regulation remains unclear.Results: Based on reanalysis of public data, we propose a negative feedback model to explain the regulation of replication and transcription in—but not limited to—CoVs. The key step leading to new discoveries was the identification of the cleavage sites of nsp15—an RNA uridylate-specific endoribonuclease, encoded by CoVs. According to this model, nsp15 regulates the synthesis of subgenomic RNAs (sgRNAs) and genomic RNAs (gRNAs) by cleaving transcription regulatory sequences in the body. The expression level of nsp15 determines the relative proportions of sgRNAs and gRNAs, which in turn change the expression level of nps15 to reach equilibrium between the replication and transcription of CoVs.Conclusions: The replication and transcription of CoVs are regulated by a negative feedback mechanism that influences the persistence of CoVs in hosts. Our findings enrich fundamental knowledge in the field of gene expression and its regulation, and provide new clues for future studies. One important clue is that nsp15 may be an important and ideal target for the development of drugs (e.g. uridine derivatives) against CoVs.

18.
researchsquare; 2020.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-93945.v1

ABSTRACT

Objectives: To analyze the epidemiological characteristics of deaths of COVID-19 in Wuhan, China and understand the changing trends of the COVID-19 epidemic and the effects of prevention and control measures in Wuhan. Methods: Through the China's Infectious Disease Information System, we collected deaths’ information in Wuhan. We analyzed the patient's demographic characteristics, drew epidemiological curve, made distribution map of epidemic situation, etc. @Risk for fitting distribution, SPSS for statistical analysis, and ArcGIS for mapping. Results: As of February 24, 2020, a total of 1833 unique deaths were extracted. Among the deaths with COVID-19, the mild type accounted for the most, 37.2%, followed by severe type, 30.1%. The median age was 70.0 (inter quartile range: 63.0-79.0) years, most of the deaths were distributed in 50-89 age group; no deaths occurred in 0-9 age group; and the male to female ratio was 1.95. A total of 65.7% of the deaths in Wuhan combined with underlying diseases, and the deaths with underlying diseases were mainly male; the main combined underlying diseases were hypertension, diabetes and cardiovascular diseases. The peak of daily deaths appeared on February 14 and then declined after February 14. The median interval from symptom onset to diagnosis was 10.0 (6.0-14.0) days; the interval from onset to diagnosis gradually shortened. The median interval from diagnosis to death was 6.0 (2.0-11.0)days; The median interval from symptom onset to deaths was 17.0 (12.0-22.0)days, respectively. In terms of geographical distribution, the central urban area was more serious. Wuchang District had the highest number of deaths, and Jianghan District had the highest death rate. Conclusion: COVID-19 posed a greater threat to the elderly and more men than women, especially elderly men with underlying diseases. The geographical distribution showed that the epidemic in the central area of Wuhan is more serious than in the surrounding areas. Analysis of deaths as of February 24 indicates that the COVID-19 epidemic in Wuhan has achieved a tremendous improvement, and the strong epidemic control measures taken by Wuhan Government were very effective.

19.
biorxiv; 2020.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2020.09.30.317818

ABSTRACT

SARS-CoV-2 infection causes an inflammatory cytokine storm and acute lung injury. Currently there are no effective antiviral and/or anti-inflammatory therapies. Here we demonstrate that 2019 SARS-CoV-2 spike protein subunit 1 (CoV2-S1) induces high levels of NF-{kappa}B activations, production of pro-inflammatory cytokines and mild epithelial damage, in human bronchial epithelial cells. CoV2-S1-induced NF-{kappa}B activation requires S1 interaction with human ACE2 receptor and early activation of endoplasmic reticulum (ER) stress, and associated unfolded protein response (UPR), and MAP kinase signalling pathways. We developed an antagonistic peptide that inhibits S1-ACE2 interaction and CoV2-S1-induced productions of pro-inflammatory cytokines. The existing FDA-approved ER stress inhibitor, 4-phenylburic acid (4-PBA), and MAP kinase inhibitors, trametinib and ulixertinib, ameliorated CoV2-S1-induced inflammation and epithelial damage. These novel data highlight the potentials of peptide-based antivirals for novel ACE2-utilising CoVs, while repurposing existing drugs may be used as treatments to dampen elevated inflammation and lung injury mediated by SARS-CoV-2.

20.
biorxiv; 2020.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2020.09.30.320903

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first discovered in December 2019 in Wuhan, China and expeditiously spread across the globe causing a global pandemic. While a select agent designation has not been made for SARS-CoV-2, closely related SARS-CoV-1 and MERS coronaviruses are classified as Risk Group 3 select agents, which restricts use of the live viruses to BSL-3 facilities. Such BSL-3 classification make SARS-CoV-2 research inaccessible to the majority of functioning research laboratories in the US; this becomes problematic when the collective scientific effort needs to be focused on such in the face of a pandemic. In this work, we assessed the four structural proteins from SARS-CoV-2 for their ability to form virus-like particles (VLPs) from human cells to form a competent system for BSL-2 studies of SARS-CoV-2. Herein, we provide methods and resources of producing, purifying, fluorescently and APEX2-labeling of SARS-CoV-2 VLPs for the evaluation of mechanisms of viral budding and entry as well as assessment of drug inhibitors under BSL-2 conditions.

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