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1.
Cell Insight ; : 100029, 2022.
Article in English | ScienceDirect | ID: covidwho-1814234

ABSTRACT

The emergence of the SARS-CoV-2 Omicron variant poses a striking threat to human society. More than 30 mutations in the Spike protein of the Omicron variant severely compromised the protective immunity elicited by either vaccination or prior infection. The persistent viral evolutionary trajectory generates Omicron-associated lineages, such as BA.1 and BA.2. Moreover, the virus recombination upon Delta and Omicron co-infections has been reported lately, although the impact remains to be assessed. This minireview summarizes the characteristics, evolution and mutation control, and immune evasion mechanisms of SARS-CoV-2 variants, which will be helpful for the in-depth understanding of the SARS-CoV-2 variants and policy-making related to COVID-19 pandemic control.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331876

ABSTRACT

Middle East Respiratory Syndrome coronavirus (MERS-CoV) and several bat coronaviruses employ Dipeptidyl peptidase-4 (DPP4) as their functional receptors. However, the receptor for NeoCoV, the closest MERS-CoV relative yet discovered in bats, remains enigmatic. In this study, we unexpectedly found that NeoCoV and its close relative, PDF-2180-CoV, can efficiently use some types of bat Angiotensin-converting enzyme 2 (ACE2) and, less favorably, human ACE2 for entry. The two viruses use their spikes' S1 subunit carboxyl-terminal domains (S1-CTD) for high-affinity and species-specific ACE2 binding. Cryo-electron microscopy analysis revealed a novel coronavirus-ACE2 binding interface and a protein-glycan interaction, distinct from other known ACE2-using viruses. We identified a molecular determinant close to the viral binding interface that restricts human ACE2 from supporting NeoCoV infection, especially around residue Asp338. Conversely, NeoCoV efficiently infects human ACE2 expressing cells after a T510F mutation on the receptor-binding motif (RBM). Notably, the infection could not be cross-neutralized by antibodies targeting SARS-CoV-2 or MERS-CoV. Our study demonstrates the first case of ACE2 usage in MERS-related viruses, shedding light on a potential bio-safety threat of the human emergence of an ACE2 using "MERS-CoV-2" with both high fatality and transmission rate.

3.
Emerg Microbes Infect ; 11(1): 567-572, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1642256

ABSTRACT

Global concern has been raised by the emergence and rapid transmission of the heavily mutated SARS-CoV-2 Omicron variant (B.1.1.529). So far, the infection features and immune escape ability of the Omicron variant have not been extensively studied. Here, we produced the Omicron pseudovirus and compared its entry, membrane fusion, and immune escape efficiency with the original strain and the dominating Delta variant. We found the Omicron variant showed slightly higher infectivity than the Delta variant and a similar ability to compete with the Delta variant in using Angiotensin-converting enzyme 2 (ACE2) in a BHK21-ACE2 cell line. However, the Omicron showed a significantly reduced fusogenicity than the original strain and the Delta variant in both BHK21-ACE2 and Vero-E6 cells. The neutralization assay testing the Wuhan convalescents' sera one-year post-infection showed a more dramatic reduction (10.15 fold) of neutralization against the Omicron variant than the Delta variant (1.79 fold) compared with the original strain with D614G. Notably, immune-boosting through three vaccine shots significantly improved the convalescents' immunity against the Omicron variants. Our results reveal a reduced fusogenicity and a striking immune escape ability of the Omicron variant, highlighting the importance of booster shots against the challenge of the SARS-CoV-2 antigenic drift.


Subject(s)
COVID-19 , SARS-CoV-2/immunology , Animals , COVID-19/immunology , Chlorocebus aethiops , Humans , Immune Evasion , Immunization, Secondary , Vero Cells
4.
Innovation (N Y) ; 3(1): 100181, 2022 Jan 25.
Article in English | MEDLINE | ID: covidwho-1595417

ABSTRACT

Most COVID-19 convalescents can build effective anti-SARS-CoV-2 humoral immunity, but it remains unclear how long it can maintain and how efficiently it can prevent the reinfection of the emerging SARS-CoV-2 variants. Here, we tested the sera from 248 COVID-19 convalescents around 1 year post-infection in Wuhan, the earliest known epicenter. SARS-CoV-2 immunoglobulin G (IgG) was well maintained in most patients and potently neutralizes the infection of the original strain and the B.1.1.7 variant. However, varying degrees of immune escape was observed on the other tested variants in a patient-specific manner, with individuals showing remarkably broad neutralization potency. The immune escape can be largely attributed to several critical spike mutations. These results suggest that SARS-CoV-2 can elicit long-lasting immunity but this is escaped by the emerging variants.

5.
China CDC Wkly ; 3(46): 967-972, 2021 Nov 12.
Article in English | MEDLINE | ID: covidwho-1513532

ABSTRACT

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently emergent coronavirus of natural origin and caused the coronavirus disease (COVID-19) pandemic. The study of its natural origin and host range is of particular importance for source tracing, monitoring of this virus, and prevention of recurrent infections. One major approach is to test the binding ability of the viral receptor gene ACE2 from various hosts to SARS-CoV-2 spike protein, but it is time-consuming and labor-intensive to cover a large collection of species. METHODS: In this paper, we applied state-of-the-art machine learning approaches and created a pipeline reaching >87% accuracy in predicting binding between different ACE2 and SARS-CoV-2 spike. RESULTS: We further validated our prediction pipeline using 2 independent test sets involving >50 bat species and achieved >78% accuracy. A large-scale screening of 204 mammal species revealed 144 species (or 61%) were susceptible to SARS-CoV-2 infections, highlighting the importance of intensive monitoring and studies in mammalian species. DISCUSSION: In short, our study employed machine learning models to create an important tool for predicting potential hosts of SARS-CoV-2 and achieved the highest precision to our knowledge in experimental validation. This study also predicted that a wide range of mammals were capable of being infected by SARS-CoV-2.

6.
BMC Psychiatry ; 21(1): 543, 2021 11 03.
Article in English | MEDLINE | ID: covidwho-1501993

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) has increased the physical and psychological stress of medical workers. This study was designed to investigate the prevalence and risk factors of job burnout and its impact on work ability among Biosafety Laboratory (BSL) staffs during the COVID-19 epidemic in Xinjiang. METHODS: A total of 7911 qualified BSL staffs in Xinjiang were investigated by electronic questionnaires. The Maslach Burnout Inventory-General Survey (MBI-GS) was used for job burnout survey. Work Ability Index (WAI) was used for work ability survey. The prevalence and risk factors of job burnout in BSL staffs were analyzed through chi square test, t-test and one-way ANOVA. And then, the influence of demographic and job-related variables, i.e., confounding factors, were eliminated to the greatest extent by the propensity score analysis (PSA) method, to investigate the impact of job burnout on work ability in BSL staffs. RESULTS: A total of 67.6% BSL staffs experienced job burnout. There were significant differences in the detection rate of job burnout among demographic and job-related variables, including gender, age, ethnicity, education, working years, professional title, marital status, number of night shift per month and overall sleep condition (all P < 0.05). The detection rate of job burnout in female was higher than that in male. The detection rates of job burnout in 45-50 years old, Han ethnicity, education of postgraduate or above, 11-20 years of working, intermediate professional title, married, staff with many night shifts per month and poor overall sleep condition were higher than that of other groups. The average burnout scores of the Emotional Exhaustion (EE), Cynicism (CY), Reduced Personal Accomplishment (PA) scale were 10.00 ± 5.99, 4.64 ± 4.59 and 15.25 ± 8.16, respectively. Multiple logistic regression analysis showed that the three dimensions of job burnout, i.e., EE, CY, PE, were negatively correlated with work ability and significantly affected the work ability of BSL staffs (all P < 0.001). CONCLUSIONS: Our results suggest that the prevalence of job burnout is extremely common among BSL staffs. In addition, the work ability decreases with the increase of job burnout and the improvement of job burnout can enhance work ability among BSL staffs.


Subject(s)
Burnout, Professional , COVID-19 , Epidemics , Burnout, Professional/epidemiology , Containment of Biohazards , Female , Humans , Job Satisfaction , Laboratories , Male , Middle Aged , SARS-CoV-2 , Surveys and Questionnaires , Work Capacity Evaluation
7.
Vaccine ; 39(48): 7001-7011, 2021 11 26.
Article in English | MEDLINE | ID: covidwho-1488001

ABSTRACT

COVID-19 pandemic has severely impacted the public health and social economy worldwide. A safe, effective, and affordable vaccine against SARS-CoV-2 infections/diseases is urgently needed. We have been developing a recombinant vaccine based on a prefusion-stabilized spike trimer of SARS-CoV-2 and formulated with aluminium hydroxide and CpG 7909. The spike protein was expressed in Chinese hamster ovary (CHO) cells, purified, and prepared as a stable formulation with the dual adjuvant. Immunogenicity studies showed that candidate vaccines elicited robust neutralizing antibody responses and substantial CD4+ T cell responses in both mice and non-human primates. And vaccine-induced neutralizing antibodies persisted at high level for at least 6 months. Challenge studies demonstrated that candidate vaccine reduced the viral loads and inflammation in the lungs of SARS-CoV-2 infected golden Syrian hamsters significantly. In addition, the vaccine-induced antibodies showed cross-neutralization activity against B.1.1.7 and B.1.351 variants. These data suggest candidate vaccine is efficacious in preventing SARS-CoV-2 infections and associated pneumonia, thereby justifying ongoing phase I/II clinical studies in China (NCT04982068 and NCT04990544).


Subject(s)
COVID-19 Vaccines , COVID-19 , Alum Compounds , Aluminum Hydroxide , Animals , Antibodies, Neutralizing , Antibodies, Viral , CHO Cells , Cricetinae , Cricetulus , Humans , Mice , Pandemics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
8.
Nat Ecol Evol ; 5(5): 600-608, 2021 05.
Article in English | MEDLINE | ID: covidwho-1111986

ABSTRACT

Bats are the suggested natural hosts for severe acute respiratory syndrome coronavirus (SARS-CoV) and the causal agent of the coronavirus disease 2019 (COVID-19) pandemic, SARS-CoV-2. The interaction of viral spike proteins with their host receptor angiotensin-converting enzyme 2 (ACE2) is a critical determinant of potential hosts and cross-species transmission. Here we use virus-host receptor binding and infection assays to examine 46 ACE2 orthologues from phylogenetically diverse bat species, including those in close and distant contact with humans. We found that 24, 21 and 16 of them failed to support infection by SARS-CoV, SARS-CoV-2 or both viruses, respectively. Furthermore, we confirmed that infection assays in human cells were consistent with those in two bat cell lines. Additionally, we used genetic and functional analyses to identify critical residues in bat ACE2 receptors associated with viral entry restrictions. Our results suggest that many bat species may not be the potential hosts of one or both viruses and that no correlation was identified between proximity to humans and probability of being natural hosts of SARS-CoV or SARS-CoV-2. This study demonstrates dramatic variation in susceptibility to SARS-CoV and SARS-CoV-2 infection among bat species and adds knowledge towards a better understanding of coronavirus-bat interaction.


Subject(s)
COVID-19 , Chiroptera , Angiotensin-Converting Enzyme 2 , Animals , Humans , Peptidyl-Dipeptidase A/genetics , Receptors, Virus/genetics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
9.
Cell Res ; 31(4): 395-403, 2021 04.
Article in English | MEDLINE | ID: covidwho-1091494

ABSTRACT

The upcoming flu season in the Northern Hemisphere merging with the current COVID-19 pandemic raises a potentially severe threat to public health. Through experimental coinfection with influenza A virus (IAV) and either pseudotyped or live SARS-CoV-2 virus, we found that IAV preinfection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Remarkably, in vivo, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice coinfected with IAV. Moreover, such enhancement of SARS-CoV-2 infectivity was not observed with several other respiratory viruses, likely due to a unique feature of IAV to elevate ACE2 expression. This study illustrates that IAV has a unique ability to aggravate SARS-CoV-2 infection, and thus, prevention of IAV infection is of great significance during the COVID-19 pandemic.


Subject(s)
COVID-19/pathology , Coinfection/pathology , Influenza A virus/physiology , Orthomyxoviridae Infections/pathology , SARS-CoV-2/physiology , Angiotensin-Converting Enzyme 2/deficiency , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/virology , Cathepsin L/genetics , Cathepsin L/metabolism , Cell Line , Coinfection/virology , Humans , Influenza A virus/isolation & purification , Lung/pathology , Mice , Mice, Transgenic , Orthomyxoviridae Infections/virology , RNA, Guide/metabolism , SARS-CoV-2/isolation & purification , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Severity of Illness Index , Viral Load , Virus Internalization
10.
Theranostics ; 10(26): 12223-12240, 2020.
Article in English | MEDLINE | ID: covidwho-934619

ABSTRACT

Rationale: Many viral infections are known to activate the p38 mitogen-activated protein kinase (MAPK) signaling pathway. However, the role of p38 activation in viral infection and the underlying mechanism remain unclear. The role of virus-hijacked p38 MAPK activation in viral infection was investigated in this study. Methods: The correlation of hepatitis C virus (HCV) infection and p38 activation was studied in patient tissues and primary human hepatocytes (PHHs) by immunohistochemistry and western blotting. Coimmunoprecipitation, GST pulldown and confocal microscopy were used to investigate the interaction of p38α and the HCV core protein. In vitro kinase assays and mass spectrometry were used to analyze the phosphorylation of the HCV core protein. Plaque assays, quantitative real time PCR (qRT-PCR), western blotting, siRNA and CRISPR/Cas9 were used to determine the effect of p38 activation on viral replication. Results: HCV infection was associated with p38 activation in clinical samples. HCV infection increased p38 phosphorylation by triggering the interaction of p38α and TGF-ß activated kinase 1 (MAP3K7) binding protein 1 (TAB1). TAB1-mediated p38α activation facilitated HCV replication, and pharmaceutical inhibition of p38α activation by SB203580 suppressed HCV infection at the viral assembly step. Activated p38α interacted with the N-terminal region of the HCV core protein and subsequently phosphorylated the HCV core protein, which promoted HCV core protein oligomerization, an essential step for viral assembly. As expected, SB203580 or the HCV core protein N-terminal peptide (CN-peptide) disrupted the p38α-HCV core protein interaction, efficiently impaired HCV assembly and impeded normal HCV replication in both cultured cells and primary human hepatocytes. Similarly, severe fever with thrombocytopenia syndrome virus (SFTSV), herpes simplex virus type 1 (HSV-1) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection also activated p38 MAPK. Most importantly, pharmacological blockage of p38 activation by SB203580 effectively inhibited SFTSV, HSV-1 and SARS-CoV-2. Conclusion: Our study shows that virus-hijacked p38 activation is a key event for viral replication and that pharmacological blockage of p38 activation is an antiviral strategy.


Subject(s)
COVID-19/metabolism , Hepacivirus/metabolism , Hepatitis C/metabolism , Mitogen-Activated Protein Kinase 14/metabolism , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , A549 Cells , Adaptor Proteins, Signal Transducing/metabolism , Animals , COVID-19/virology , Chlorocebus aethiops , Enzyme Activation , HEK293 Cells , Hepatitis C/pathology , Hepatitis C/virology , Hepatocytes/metabolism , Humans , Imidazoles/pharmacology , MAP Kinase Kinase Kinases/metabolism , MAP Kinase Signaling System/drug effects , Mitogen-Activated Protein Kinase 14/antagonists & inhibitors , Phosphorylation , Pyridines/pharmacology , Vero Cells , Viral Core Proteins/metabolism , Virus Replication/drug effects
11.
Medicine (Baltimore) ; 99(37): e22109, 2020 Sep 11.
Article in English | MEDLINE | ID: covidwho-760048

ABSTRACT

BACKGROUND: Patients with the Corona Virus Disease 2019 (COVID-19) often see their respiratory, physical, and psychological functions impaired to varying degrees, especially for the elderly patients. Timely respiratory rehabilitation intervention for such patients may improve their prognoses. However, its relative effectiveness has not been proved. Therefore, this study is purposed to determine the effect of respiratory rehabilitation on elderly patients with COVID-19. METHODS: This study will search the following electronic databases: Embase, MEDLINE, PubMed, Cochrane Library, China national knowledge infrastructure database, Wan Fang database, Chinese Science and Technology Periodical Database, and Chinese Biomedical Literature Database, with the retrieval period running from their inception to August 2020. All randomized controlled trials of respiratory rehabilitation training on elderly patients with COVID-19 are collected, and the data are selected and extracted independently according to the pre-designed inclusion/exclusion criteria. Cochrane bias risk assessment tool is used to evaluate the method quality and bias risk. All data analyses will be implemented by using Revman5.3 and Stata14 software. RESULTS: This study will make a high-quality and comprehensive evaluation of the efficacy of respiratory rehabilitation training on elderly patients with COVID-19. CONCLUSION: The conclusions of this systematic review will deliver more convincing evidence. ETHICS AND DISSEMINATION: The private information collected from individuals will not be published. And this systematic review will also not involve impairing the participants' rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.


Subject(s)
Breathing Exercises , Coronavirus Infections , Pandemics , Pneumonia, Viral , Psychosocial Support Systems , Aged , Betacoronavirus , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/psychology , Coronavirus Infections/rehabilitation , Humans , Meta-Analysis as Topic , Pneumonia, Viral/epidemiology , Pneumonia, Viral/psychology , Pneumonia, Viral/rehabilitation , Prognosis , Research Design , SARS-CoV-2 , Systematic Reviews as Topic , Treatment Outcome
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