Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 10 de 10
Filter
1.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1871974

ABSTRACT

The continuous spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world has raised unprecedented challenges to the human society. Antibodies and nanobodies possessing neutralization activity represent promising drug candidates. In this study, we report the identification and characterization of a potent SARS-CoV-2 neutralizing nanobody that targets the viral spike receptor-binding domain (S-RBD). The nanobody, termed as Nb-007, engages SARS-CoV-2 S-RBD with the two-digit picomolar binding affinity and shows outstanding virus entry-inhibition activity. The complex structure of Nb-007 bound to SARS-CoV-2 S-RBD reveals an epitope that is partially overlapping with the binding site for the human receptor of angiotensin-converting enzyme 2 (ACE2). The nanobody therefore exerts neutralization by competing with ACE2 for S-RBD binding, which is further ascertained by our in-vitro biochemical analyses. Finally, we also show that Nb-007 reserves promising, though compromised, neutralization activity against the currently-circulating Delta variant and that fusion of the nanobody with Fc dramatically increases its entry-inhibition capacity. Taken together, these data have paved the way of developing Nb-007 as a drug-reserve for potential treatment of SARS-CoV-2 related diseases.

2.
Non-conventional in English | Social Science Open Access Repository, Grey literature | ID: grc-747788

ABSTRACT

Purpose: This study investigates Chinese college students' satisfaction with using e-learning systems and its influences on their sense of online classroom community in synchronous, asynchronous, or a blend of both synchronous and asynchronous online course format during the COVID-19 pandemic. Methods: A total number of 307 college students were recruited with 270 usable responses from a southeastern university in China. E-learner satisfaction measurement and Classroom Community Scale (both with a 5-point Likert-type scale) were used as the instruments to investigate the research questions. Descriptive statistical analysis and multiple regression analysis were conducted in SPSS. Results: Results of the analysis show that Chinese college students' satisfaction of using the e-learning system regarding the learner interface, learning community, content, and personalization positively impacts their sense of online classroom community no matter in synchronous, asynchronous, or a blend of both synchronous and asynchronous online course format. Implications: A well-developed e-learning system would enhance students' sense of online classroom community. Specifically, the user interface, interaction, content arrangement, and personalization should be focused on when developing the e-learning system.

3.
International Journal of Psychology and Educational Studies ; 8(3):116-127, 2021.
Article in English | ProQuest Central | ID: covidwho-1459647

ABSTRACT

In the spring semester of 2020, all Chinese higher education institutions delivered courses online across the nation in response to the COVID-19. This study explores Chinese college students' self-regulated learning, academic entitlement, and academic achievement during the transitioning from face-to-face to online learning environments during this special time. Structure equation modeling was conducted, and results indicate that academic entitlement associates with students' online learning academic achievement. Whereas self-regulated learning does not relate to academic achievement in the online learning setting. Additionally, academic entitlement is marginally associated with academic achievement only among male students, while self-regulated learning is not a significant predictor for both genders. However, self-regulated learning is marginally linked with higher academic achievement among students who do not have previous online learning experiences but not among those who took online courses before.

4.
Signal Transduct Target Ther ; 6(1): 343, 2021 09 16.
Article in English | MEDLINE | ID: covidwho-1415924

ABSTRACT

SARS-CoV-2 recognizes, via its spike receptor-binding domain (S-RBD), human angiotensin-converting enzyme 2 (ACE2) to initiate infection. Ecto-domain protein of ACE2 can therefore function as a decoy. Here we show that mutations of S19W, T27W, and N330Y in ACE2 could individually enhance SARS-CoV-2 S-RBD binding. Y330 could be synergistically combined with either W19 or W27, whereas W19 and W27 are mutually unbeneficial. The structures of SARS-CoV-2 S-RBD bound to the ACE2 mutants reveal that the enhanced binding is mainly contributed by the van der Waals interactions mediated by the aromatic side-chains from W19, W27, and Y330. While Y330 and W19/W27 are distantly located and devoid of any steric interference, W19 and W27 are shown to orient their side-chains toward each other and to cause steric conflicts, explaining their incompatibility. Finally, using pseudotyped SARS-CoV-2 viruses, we demonstrate that these residue substitutions are associated with dramatically improved entry-inhibition efficacy toward both wild-type and antibody-resistant viruses. Taken together, our biochemical and structural data have delineated the basis for the elevated S-RBD binding associated with S19W, T27W, and N330Y mutations in ACE2, paving the way for potential application of these mutants in clinical treatment of COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/chemistry , COVID-19 , Molecular Dynamics Simulation , Mutation, Missense , SARS-CoV-2/chemistry , Amino Acid Substitution , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Viral/chemistry , Antibodies, Viral/metabolism , Humans , SARS-CoV-2/genetics , SARS-CoV-2/metabolism
5.
Nucleic Acids Res ; 49(9): 5382-5392, 2021 05 21.
Article in English | MEDLINE | ID: covidwho-1387965

ABSTRACT

The emergence of SARS-CoV-2 infection has posed unprecedented threat to global public health. The virus-encoded non-structural protein 14 (nsp14) is a bi-functional enzyme consisting of an exoribonuclease (ExoN) domain and a methyltransferase (MTase) domain and plays a pivotal role in viral replication. Here, we report the structure of SARS-CoV-2 nsp14-ExoN domain bound to its co-factor nsp10 and show that, compared to the SARS-CoV nsp10/nsp14-full-length complex, SARS-CoV-2 nsp14-ExoN retains an integral exoribonuclease fold and preserves an active configuration in the catalytic center. Analysis of the nsp10/nsp14-ExoN interface reveals a footprint in nsp10 extensively overlapping with that observed in the nsp10/nsp16 structure. A marked difference in the co-factor when engaging nsp14 and nsp16 lies in helix-α1', which is further experimentally ascertained to be involved in nsp14-binding but not in nsp16-engagement. Finally, we also show that nsp10/nsp14-ExoN is enzymatically active despite the absence of nsp14-MTase domain. These data demonstrate that SARS-CoV-2 nsp10/nsp14-ExoN functions as an exoribonuclease with both structural and functional integrity.


Subject(s)
Biocatalysis , Exoribonucleases/chemistry , Exoribonucleases/metabolism , SARS-CoV-2/chemistry , SARS-CoV-2/enzymology , Viral Nonstructural Proteins/chemistry , Viral Nonstructural Proteins/metabolism , Viral Regulatory and Accessory Proteins/chemistry , Viral Regulatory and Accessory Proteins/metabolism , Binding Sites , Crystallography, X-Ray , Exoribonucleases/genetics , Guanine , Methyltransferases/chemistry , Methyltransferases/deficiency , Methyltransferases/genetics , Methyltransferases/metabolism , Models, Molecular , Protein Domains/genetics , SARS-CoV-2/genetics , Viral Nonstructural Proteins/genetics , Viral Regulatory and Accessory Proteins/genetics
6.
Nucleic Acids Res ; 49(9): 5382-5392, 2021 05 21.
Article in English | MEDLINE | ID: covidwho-1217861

ABSTRACT

The emergence of SARS-CoV-2 infection has posed unprecedented threat to global public health. The virus-encoded non-structural protein 14 (nsp14) is a bi-functional enzyme consisting of an exoribonuclease (ExoN) domain and a methyltransferase (MTase) domain and plays a pivotal role in viral replication. Here, we report the structure of SARS-CoV-2 nsp14-ExoN domain bound to its co-factor nsp10 and show that, compared to the SARS-CoV nsp10/nsp14-full-length complex, SARS-CoV-2 nsp14-ExoN retains an integral exoribonuclease fold and preserves an active configuration in the catalytic center. Analysis of the nsp10/nsp14-ExoN interface reveals a footprint in nsp10 extensively overlapping with that observed in the nsp10/nsp16 structure. A marked difference in the co-factor when engaging nsp14 and nsp16 lies in helix-α1', which is further experimentally ascertained to be involved in nsp14-binding but not in nsp16-engagement. Finally, we also show that nsp10/nsp14-ExoN is enzymatically active despite the absence of nsp14-MTase domain. These data demonstrate that SARS-CoV-2 nsp10/nsp14-ExoN functions as an exoribonuclease with both structural and functional integrity.


Subject(s)
Biocatalysis , Exoribonucleases/chemistry , Exoribonucleases/metabolism , SARS-CoV-2/chemistry , SARS-CoV-2/enzymology , Viral Nonstructural Proteins/chemistry , Viral Nonstructural Proteins/metabolism , Viral Regulatory and Accessory Proteins/chemistry , Viral Regulatory and Accessory Proteins/metabolism , Binding Sites , Crystallography, X-Ray , Exoribonucleases/genetics , Guanine , Methyltransferases/chemistry , Methyltransferases/deficiency , Methyltransferases/genetics , Methyltransferases/metabolism , Models, Molecular , Protein Domains/genetics , SARS-CoV-2/genetics , Viral Nonstructural Proteins/genetics , Viral Regulatory and Accessory Proteins/genetics
7.
Transp Policy (Oxf) ; 104: 29-42, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1080519

ABSTRACT

Within half a year, COVID-19 spreads to most countries in the world, as well as posed a great threat to the public health of human beings. The implementation of non-pharmaceutical intervention (NPI), including travel ban, proved to be an effective way for controlling the epidemic spreading, e.g., the ban of inter-city transportation stops transporting virus through passengers between cities. However, travel ban could significantly impact many industries, e.g. tourism and logistics, thus jeopardizing the regional economy. This paper focus on assisting the national or regional government to make dynamic decisions on restricting and recovering intercity multi-modal travel services. Our model can characterize impacts of inter-city traffic on the spread of the COVID-19, as well as on the regional economy. By applying a reinforcement learning approach, we develop an online optimization model to identify the modal-specific travel banning strategy that can balance the epidemic control as well as the negative impacts on regional economy. The numerical study based on a network of multiple cities in China shows that the proposed approach can generate better strategies compared with some existing methods.

8.
J Infect ; 81(4): e18-e25, 2020 10.
Article in English | MEDLINE | ID: covidwho-629626

ABSTRACT

OBJECTIVE: Coronavirus Disease 2019 (COVID-19) is a pandemic. This systematic review compares mortality risk factors including clinical, demographic and laboratory features of COVID-19, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The aim is to provide new strategies for COVID-19 prevention and treatment. METHODS: We performed a systematic review with meta-analysis, using five databases to compare the predictors of death for COVID-19, SARS and MERS. A random-effects model meta-analysis calculated odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: 845 articles up through 11/4/2020 were retrieved, but only 28 studies were included in this meta-analysis. The results showed that males had a higher likelihood of death than females (OR = 1.82, 95% CI 1.56-2.13). Age (OR = 7.86, 95% CI 5.46-11.29), diabetes comorbidity (OR = 3.73, 95% CI 2.35-5.90), chronic lung disease (OR = 3.43, 95% CI 1.80-6.52) and hypertension (OR = 3.38, 95% CI 2.45-4.67) were the mortality risk factors. The laboratory indicators lactic dehydrogenase (OR = 37.52, 95% CI 24.68-57.03), C-reactive protein (OR = 12.11, 95% CI 5.24-27.98), and neutrophils (OR = 17.56, 95% CI 10.67-28.90) had stronger correlations with COVID-19 mortality than with SARS or MERS mortality. Consolidation and ground-glass opacity imaging features were similar among COVID-19, SARS, and MERS patients. CONCLUSIONS: COVID-19's mortality factors are similar to those of SARS and MERS. Age and laboratory indicators could be effective predictors of COVID-19 mortality outcomes.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , Risk Factors , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/mortality , Betacoronavirus , C-Reactive Protein/analysis , COVID-19 , Diabetes Mellitus/pathology , Female , Humans , Hypertension/pathology , L-Lactate Dehydrogenase/blood , Lung Diseases/pathology , Male , Middle East Respiratory Syndrome Coronavirus , Neutrophils/cytology , Pandemics , SARS Virus , SARS-CoV-2 , Sex Factors
10.
J Pain Symptom Manage ; 60(1): e60-e65, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-196669

ABSTRACT

CONTEXT: The epidemic of coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China and has now spread worldwide. In the affected countries, physicians and nurses are under heavy workload conditions and are at high risk of infection. OBJECTIVES: The aim of this study was to compare the frequency of burnout between physicians and nurses on the frontline (FL) wards and those working in usual wards (UWs). METHODS: A survey with a total of 49 questions was administered to 220 medical staff members from the COVID-19 FL and UWs, with a ratio of 1:1. General information, such as age, gender, marriage status, and the Maslach Burnout Inventory-medical personnel, were gathered and compared. RESULTS: The group working on the FLs had a lower frequency of burnout (13% vs. 39%; P < 0.0001) and were less worried about being infected compared with the UW group. CONCLUSION: Compared with medical staff working on their UWs for uninfected patients, medical staff working on the COVID-19 FL ward had a lower frequency of burnout. These results suggest that in the face of the COVID-19 crisis, both FL ward and UW staff should be considered when policies and procedures to support the well-being of health care workers are devised.


Subject(s)
Burnout, Professional/epidemiology , Coronavirus Infections/therapy , Epidemics , Hospital Units , Nurses/psychology , Physicians/psychology , Pneumonia, Viral/therapy , Adult , Attitude of Health Personnel , COVID-19 , China/epidemiology , Cities/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/psychology , Fear , Female , Humans , Male , Medical Oncology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/psychology , Specialization
SELECTION OF CITATIONS
SEARCH DETAIL