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1.
Frontiers in cell and developmental biology ; 10, 2022.
Article in English | EuropePMC | ID: covidwho-1871159

ABSTRACT

The COVID-19 pandemic caused by the severe acute coronavirus disease 2 (SARS-CoV-2) virus represents an ongoing threat to human health and well-being. Notably, many COVID-19 patients suffer from complications consistent with osteoporosis (OP) following disease resolution yet the mechanistic links between SARS-CoV-2 infection and OP remain to be clarified. The present study was thus developed to explore the potential basis for this link by employing transcriptomic analyses to identify signaling pathways and biomarkers associated with OP and SARS-CoV-2. Specifically, a previously published RNA-sequencing dataset (GSE152418) from Gene Expression Omnibus (GEO) was used to identify the differentially expressed genes (DEGs) in OP patients and individuals infected with SARS-CoV-2 as a means of exploring the underlying molecular mechanisms linking these two conditions. In total, 2,885 DEGs were identified by analyzing the COVID-19 patient dataset, with shared DEGs then being identified by comparison of these DEGs with those derived from an OP patient dataset. Hub genes were identified through a series of bioinformatics approaches and protein-protein interaction analyses. Predictive analyses of transcription factor/gene interactions, protein/drug interactions, and DEG/miRNA networks associated with these DEGs were also conducted. Together, these data highlight promising candidate drugs with the potential to treat both COVID-19 and OP.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-337676

ABSTRACT

Protein-biomolecule interactions play pivotal roles in almost all biological processes, the identification of the interacting protein is essential. By combining a substrate-based proximity labelling activity from the pupylation pathway of Mycobacterium tuberculosis , and the streptavidin (SA)-biotin system, we developed S pecific P upylation as IDE ntity R eporter (SPIDER) for identifying protein-biomolecular interactions. As a proof of principle, SPIDER was successfully applied for global identification of interacting proteins, including substrates for enzyme (CobB), the readers of m 6 A, the protein interactome of mRNA, and the target proteins of drug (lenalidomide). In addition, by SPIDER, we identified SARS-CoV-2 Omicron variant specific receptors on cell membrane and performed in-depth analysis for one candidate, Protein-g. These potential receptors could explain the differences between the Omicron variant and the Prototype strain, and further serve as target for combating the Omicron variant. Overall, we provide a robust technology which is applicable for a wide-range of protein-biomolecular interaction studies.

3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329783

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with immune escape ability raises the urgent need for developing cross-neutralizing vaccines against the virus. NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluated the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in adults previously vaccinated with the inactivated vaccine BBIBP-CorV in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates ( NCT05069129 ). Three groups of healthy adults over 18 years of age (600 participants per group) who had administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, were vaccinated with either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The primary outcome was immunogenicity and safety of booster vaccinations. The exploratory outcome was cross-reactive immunogenicity against multiple SARS-CoV-2 variants of concerns (VOCs). The incidence of adverse reactions was low in both booster vaccinations, and the overall safety profile of heterologous boost was quite similar to that of homologous boost. Heterologous NVSI-06-08 booster was immunogenically superior to homologous booster of BBIBP-CorV. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster were significantly higher than by the booster of BBIBP-CorV against not only SARS-CoV-2 prototype strain but also multiple VOCs. Especially, the neutralizing activity induced by NVSI-06-08 booster against the immune-evasive Beta variant was no less than that against the prototype strain, and a considerable level of neutralizing antibodies against Omicron (GMT: 367.67;95%CI, 295.50-457.47) was induced by heterologous booster, which was substantially higher than that boosted by BBIBP-CorV (GMT: 45.03;95%CI, 36.37-55.74). Our findings showed that NVSI-06-08 was safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which was immunogenically superior to homologous boost with another dose of BBIBP-CorV. Our study also indicated that the design of hybrid antigen may provide an effective strategy for broad-spectrum vaccine developments.

4.
International Journal of Sustainable Transportation ; : 1-11, 2022.
Article in English | Taylor & Francis | ID: covidwho-1730516
5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-313415

ABSTRACT

Objectives: To provide a reference for CT imaging changes for patients discharged from a Fangcang shelter hospital, a large-scale, temporary hospital for the centralized treatment of patients with mild to moderate Coronavirus disease 2019 (COVID-19) to provide essential functions (isolation, triage, basic medical care, frequent monitoring and rapid referral, essential living and social engagement) to them.. Methods: : Patients with mild to moderate COVID-19 admitted to the Wuchang Fangcang Shelter Hospital who had undergone pre-discharge and previous CT scans were included. Changes in the CT imaging features were defined as progression, no change, improvement or recovery. Basic patient information was obtained, and imaging signs were compared between the two CT scans. Results: : A total of 83 patients were included. The median age was 53 years old. The course of disease was 28.3±10.7 days. CT imaging changes indicated progression, no change, improvement, and recovery in 3, 12, 66, and 2 patients, respectively. Between the two CT scans, the imaging signs showed a significant reduction in consolidation, a significant increase in fibrosis, and a reduction or / and thinning of ground-glass opacities. None of the patients showed signs of deterioration on follow-up and thus did not need to return to the hospital for treatment. Conclusion: In the COVID-19 Fangcang shelter hospital, given the shortage of medical staff and lack of medical resources, CT imaging diagnostic methods can be used to accurately discharge patients who had met the discharge criteria for isolation and observation from the Fangcang Shelter Hospital.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312719

ABSTRACT

The pandemic Coronavirus Disease 2019 (COVID-19) causes noticeable morbidity and mortality worldwide. In addition to vaccine and antiviral drug therapy, the use of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) neutralizing antibodies for treatment purposes is a viable alternative. In this study, we aimed to profile the humoral responses and identify neutralizing antibodies against SARS-CoV-2 using high-throughput single-cell sequencing that tailored to B cell receptor sequencing. From two convalescent patients with high serum titer against SARS-COV-2, we identified seven antibodies specifically binding to SARS-CoV-2. Among these, the most potent antibody, P4A1 was demonstrated to block the binding of spike protein to its receptor angiotensin-converting enzyme 2 (ACE2), and prevent the viral infection in neutralization assays with pseudovirus as well as live virus at nM to sub-nM range. Moreover, antibody P4A1 can also bind strongly to spike protein with N354D/D364Y, R408I, W436R, V367F or D614G mutations respectively, suggesting that the antibody alone or in combination with other antibodies that recognize different variations of SARS-CoV-2, may provide a broad spectrum therapeutic option for COVID-19 patients. Authors Lisu Huang, Bingqing Shen, Yu Guo, and Shu Shen contributed equally to this work.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-309638

ABSTRACT

CTSL is one of the SARS-entry-associated CoV-2's proteases and plays a key role in the virus's entry into the cell and subsequent infection. We investigated the association between the expression level of CTSL and overall survival in TCGA and CGGA databases, in order to better understand the possible route and risks of new coronavirus infection for patients with GBM. Meanwhile, the relationship between CTSL and immune infiltration levels was analyzed by means of the TIMER database. The impact of CTSL inhibitors on GBM biological activity was tested. The findings revealed that GBM tissues had higher CTSL expression levels than that of normal brain tissues, which was associated with a significantly lower survival rate in GBM patients. Meanwhile, CTSL was very negatively correlated with purity, B cell and CD8 + T cell in GBM. CTSL inhibitor significantly reduced U251 cell growth and invasion in vitro and induced mitochondrial apoptosis. According to the findings of this study, CTSL acts as an independent prognostic factor and can be considered as promising therapeutic target for GBM.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325222

ABSTRACT

BACKGROUND: Previous study suggested that Chinese Herbal Medicine (CHM) Formula Huashibaidu granule might shorten disease course of Corona Virus Disease 2019 (COVID-19) patients. Our research aims to investigate the early treatment effect of Huashibaidu granule in mild COVID-19 patients under well clinical management.METHODS: An unblended cluster-randomized clinical trial was conducted at the Dongxihu FangCang hospital. 2 cabins were randomly allocated to CHM or control group, with 204 randomly sampled mild COVID-19 patients in each cabin. All participants received a 7-day conventional treatment, and CHM group cabin used additional Huashibaidu granule 10g twice daily. Participants were followed up until they met clinical endpoint. The primary outcome was patient become worsening before clinical endpoint occurred. The secondary outcomes was discharge with cure before clinical endpoint occurred and relief of composite symptoms after 7 days treatment.FINDINGS: All 408 participants were followed up to meet clinical endpoint and included in statistical analysis. The baseline characteristics were comparable between 2 groups. The number of worsening patients in the CHM group was 5 (2.5%), and that in the control group was 16 (7.8%). There was a significant difference between groups (P=0.014). 8 foreseeable mild adverse events occurred without statistical difference between groups.INTERPRETATION: 7-day early treatment with Huashibaidu granule reduced worsening conversion of mild COVID-19 patients. Our study supports Huashibaidu Granule as an active option for early treatment of mild COVID-19 in similar medical locations with well management.TRIAL REGISTRATION: The Chinese Clinical Trial Registry: ChiCTR2000029763.FUNDING: This study was supported by “National Key R&D Program of China” (No.2020YFC0841500).DECLARATION OF INTERESTS: The authors guaranteed that there existed no competing interest in this paper.ETHICS APPROVAL STATEMENT: Ethics Review Committee of Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences Approval of Ethical Review Acceptance Number: S2020-001;Approval Number: P20001/PJ01.

9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-292884

ABSTRACT

Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2);however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 day and 7 days after single-dose vaccination or 6 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight, caused by either the prototype-like strain or beta variant of SARS-CoV-2. Lasted data showed that the animals could be well protected against beta variant challenge 9 months after vaccination. Notably, the weight loss and lung pathological changes of hamsters could still be significantly reduced when the hamster was vaccinated 24 h after challenge. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to fight against the ongoing COVID-19 pandemic, compensating limitations of current intramuscular vaccines, particularly at the start of an outbreak.

10.
Preprint in English | bioRxiv | ID: ppbiorxiv-468472

ABSTRACT

Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 day and 7 days after single-dose vaccination or 6 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight, caused by either the prototype-like strain or beta variant of SARS-CoV-2. Lasted data showed that the animals could be well protected against beta variant challenge 9 months after vaccination. Notably, the weight loss and lung pathological changes of hamsters could still be significantly reduced when the hamster was vaccinated 24 h after challenge. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to fight against the ongoing COVID-19 pandemic, compensating limitations of current intramuscular vaccines, particularly at the start of an outbreak.

12.
Preprint in English | medRxiv | ID: ppmedrxiv-21259838

ABSTRACT

Mesenchymal stem cells (MSCs) therapy is considered one of the most promising treatments in the context of the coronavirus disease 2019 (COVID-19) pandemic. However, the safety and effectiveness of MSCs in the treatment of COVID-19-associated pneumonia patients need to be systematically reviewed and analyzed. Two independent researchers searched for the relevant studies published between October 2019 and April 2021 in PubMed, Embase, Cochrane Library, WAN FANG, and CNKI databases. A total of 22 studies involving 371 patients were included in the present study. MSCs were administered in 247 participants, and MSCs were allogeneic from umbilical cord, adipose tissue, menstrual blood, placenta, Whartons jelly, or unreported sources. Combined results found that MSCs group significantly reduced the incidence of adverse events (OR = 0.43, 95%CI. = 0.22[~]0.84, P = 0.01) and mortality (OR = 0.17, 95%CI. = 0.06[~]0.49, P < 0.01), and the difference compared with control group was statistically significant. No MSCs treat-related serious adverse events were reported. The lung function and radiographic outcomes, and biomarker levels of inflammation and immunity all showed improvement trends. Therefore, MSCs therapy is an effective and safe method in the treatment of COVID-19-associated pneumonia and shows advantages in less adverse events and mortality. However, a standard and effective MSCs treatment program needs to be developed.

13.
Journal of Loss Prevention in the Process Industries ; : 104583, 2021.
Article in English | ScienceDirect | ID: covidwho-1284226

ABSTRACT

The COVID-19 epidemic has caused a lack of data on highway transportation accidents involving dangerous goods in China in the first quarter of 2020, and this lack of data has seriously affected research on highway transportation accidents involving dangerous goods. This study strives to compensate for this lack to a certain extent and reduce the impact of missing data on research of dangerous goods transportation accidents. Data pertaining to 2340 dangerous goods accidents in the process of highway transportation in China from 2013 to 2019 are obtained with webpage crawling software. In this paper, the number of monthly highway transportation accidents involving dangerous goods from 2013 to 2019 is determined, and the time series of transportation accidents and an autoregressive moving average (ARMA) prediction model are established. The prediction accuracy of the model is evaluated based on the actual number of dangerous goods highway transportation accidents in China from 2017 to 2019. The results indicate that the mean absolute percentage error (MAPE) between the actual and predicted values of dangerous goods highway transportation accidents from 2017 to 2019 is 0.147, 0.315 and 0.29. Therefore, the model meets the prediction accuracy requirements. Then, the prediction model is applied to predict the number of dangerous goods transportation accidents in the first quarter of 2020 in China. Twenty-two accidents are predicted in January, 23 accidents in February and 27 accidents in March. The results provide a reference for the study of dangerous goods transportation accidents and the formulation of accident prevention and emergency measures.

14.
Journal of Physics: Conference Series ; 1931(1), 2021.
Article in English | ProQuest Central | ID: covidwho-1280023

ABSTRACT

The employment situation in civil aviation has become more severe this year due to the adverse effects of the COVID-19 epidemic. The online teaching of employment guidance courses can promote high-quality employment for graduates, but also poses new challenges for teachers and students. For college students enrolled in 2018 majoring in civil aviation, the teachers in the Civil Aviation Management Institute of China accomplished the employment guidance course, adopting a teaching method combining online teaching with offline guidance, and applying the Deming cycle to continuously improve the course quality. To facilitate better employment of civil aviation graduates under the epidemic, this paper suggests that it is necessary to establish an employment guidance and service system, improve the comprehensive quality of graduates, promote cooperation and mutual assistance between schools and employers, and guide graduates to start their businesses or further study rationally.

15.
SciFinder; 2020.
Preprint | SciFinder | ID: ppcovidwho-5156

ABSTRACT

To introduce the management measures in stomatol. emergency during the epidemic period of corona virus disease 2019 (COVID-19). The overall plan is to implement strict district management, standardized medical management, and scientific patient and accompany management. We′d better to focus on the effective pre-check and triage of patients and emergency infection control training for medical staff. The prevention and disinfection of splash treatment should be paid attention especially Meanwhile, it′s very important to establish the system of trace management and real-time patient follow i.p., provide targeted Psycol. guidance for doctor and patient, and constantly improve the stomatol. emergency system. All the measures are to provide references for oral health care personnel to win the battle of COVID-19.

16.
Preprint in English | bioRxiv | ID: ppbiorxiv-424617

ABSTRACT

Many RNAs fold into multiple structures at equilibrium. The classical stochastic sampling algorithm can sample secondary structures according to their probabilities in the Boltzmann ensemble, and is widely used. However, this algorithm, consisting of a bottom-up partition function phase followed by a top-down sampling phase, suffers from three limitations: (a) the formulation and implementation of the sampling phase are unnecessarily complicated; (b) the sampling phase repeatedly recalculates many redundant recursions already done during the partition function phase; (c) the partition function runtime scales cubically with the sequence length. These issues prevent stochastic sampling from being used for very long RNAs such as the full genomes of SARS-CoV-2. To address these problems, we first adopt a hypergraph framework under which the sampling algorithm can be greatly simplified. We then present three sampling algorithms under this framework, among which the LazySampling algorithm is the fastest by eliminating redundant work in the sampling phase via on-demand caching. Based on LazySampling, we further replace the cubic-time partition function by a linear-time approximate one, and derive LinearSampling, an end-to-end linear-time sampling algorithm that is orders of magnitude faster than the standard one. For instance, LinearSampling is 176x faster (38.9s vs. 1.9h) than Vienna RNAsubopt on the full genome of Ebola virus (18,959 nt). More importantly, LinearSampling is the first RNA structure sampling algorithm to scale up to the full-genome of SARS-CoV-2 without local window constraints, taking only 69.2 seconds on its reference sequence (29,903 nt). The resulting sample correlates well with the experimentally-guided structures. On the SARS-CoV-2 genome, LinearSampling finds 23 regions of 15 nt with high accessibilities, which are potential targets for COVID-19 diagnostics and drug design. See code: https://github.com/LinearFold/LinearSampling

17.
Preprint in English | bioRxiv | ID: ppbiorxiv-423552

ABSTRACT

A safe and effective SARS-CoV-2 vaccine is essential to avert the on-going COVID-19 pandemic. Here, we developed a subunit vaccine, which is comprised of CHO-expressed spike ectodomain protein (StriFK) and nitrogen bisphosphonates-modified zinc-aluminum hybrid adjuvant (FH002C). This vaccine candidate rapidly elicited the robust humoral response, Th1/Th2 balanced helper CD4 T cell and CD8 T cell immune response in animal models. In mice, hamsters, and non-human primates, 2-shot and 3-shot immunization of StriFK-FH002C generated 28- to 38-fold and 47- to 269-fold higher neutralizing antibody titers than the human COVID-19 convalescent plasmas, respectively. More importantly, the StriFK-FH002C immunization conferred sterilizing immunity to prevent SARS-CoV-2 infection and transmission, which also protected animals from virus-induced weight loss, COVID-19-like symptoms, and pneumonia in hamsters. Vaccine-induced neutralizing and cell-based receptor-blocking antibody titers correlated well with protective efficacy in hamsters, suggesting vaccine-elicited protection is immune-associated. The StriFK-FH002C provided a promising SARS-CoV-2 vaccine candidate for further clinical evaluation.

18.
Preprint in English | bioRxiv | ID: ppbiorxiv-393488

ABSTRACT

The constant emergence of COVID-19 variants reduces the effectiveness of existing vaccines and test kits. Therefore, it is critical to identify conserved structures in SARS-CoV-2 genomes as potential targets for variant-proof diagnostics and therapeutics. However, the algorithms to predict these conserved structures, which simultaneously fold and align multiple RNA homologs, scale at best cubically with sequence length, and are thus infeasible for coronaviruses, which possess the longest genomes ([~]30,000 nt) among RNA viruses. As a result, existing efforts on modeling SARS-CoV-2 structures resort to single sequence folding as well as local folding methods with short window sizes, which inevitably neglect long-range interactions that are crucial in RNA functions. Here we present LinearTurboFold, an efficient algorithm for folding RNA homologs that scales linearly with sequence length, enabling unprecedented global structural analysis on SARS-CoV-2. Surprisingly, on a group of SARS-CoV-2 and SARS-related genomes, LinearTurbo-Folds purely in silico prediction not only is close to experimentally-guided models for local structures, but also goes far beyond them by capturing the end-to-end pairs between 5 and 3 UTRs ([~]29,800 nt apart) that match perfectly with a purely experimental work. Furthermore, LinearTurboFold identifies novel conserved structures and conserved accessible regions as potential targets for designing efficient and mutation-insensitive small-molecule drugs, antisense oligonucleotides, siRNAs, CRISPR-Cas13 guide RNAs and RT-PCR primers. LinearTurboFold is a general technique that can also be applied to other RNA viruses and full-length genome studies, and will be a useful tool in fighting the current and future pandemics. Significance StatementConserved RNA structures are critical for designing diagnostic and therapeutic tools for many diseases including COVID-19. However, existing algorithms are much too slow to model the global structures of full-length RNA viral genomes. We present LinearTurboFold, a linear-time algorithm that is orders of magnitude faster, making it the first method to simultaneously fold and align whole genomes of SARS-CoV-2 variants, the longest known RNA virus ([~]30 kilobases). Our work enables unprecedented global structural analysis and captures long-range interactions that are out of reach for existing algorithms but crucial for RNA functions. LinearTurboFold is a general technique for full-length genome studies and can help fight the current and future pandemics.

19.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-515

ABSTRACT

Background: The outbreak of a new coronavirus (2019-nCoV) induced pneumonia (NCP) in the central city of Wuhan in China poses a threat to the public health. Thi

20.
Preprint in English | bioRxiv | ID: ppbiorxiv-215236

ABSTRACT

The ongoing COVID-19 pandemic, caused by SARS-CoV-2 infection, has resulted in hundreds of thousands of deaths. Cellular entry of SARS-CoV-2, which is mediated by the viral spike protein and host ACE2 receptor, is an essential target for the development of vaccines, therapeutic antibodies, and drugs. Using a mammalian cell expression system, we generated a recombinant fluorescent protein (Gamillus)-fused SARS-CoV-2 spike trimer (STG) to probe the viral entry process. In ACE2-expressing cells, we found that the STG probe has excellent performance in the live-cell visualization of receptor binding, cellular uptake, and intracellular trafficking of SARS-CoV-2 under virus-free conditions. The new system allows quantitative analyses of the inhibition potentials and detailed influence of COVID-19-convalescent human plasmas, neutralizing antibodies and compounds, providing a versatile tool for high-throughput screening and phenotypic characterization of SARS-CoV-2 entry inhibitors. This approach may also be adapted to develop a viral entry visualization system for other viruses.

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