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1.
Discrete Dynamics in Nature & Society ; : 1-6, 2022.
Article in English | Academic Search Complete | ID: covidwho-1861704

ABSTRACT

Objectives. The statistical characteristics of incubation time of COVID-19 are studied comprehensively in this paper. We studied the mean value and tail characteristic of incubation time. Also, the difference in incubation time is studied in different age groups, different genders, and different contact modes. Methods. We analyzed the data by a lognormal distribution. Tail characteristics of incubation time are studied by the excess function. The difference in incubation time between different age groups, different genders, and different contact modes is studied by one-way ANOVA. Results. The results showed that the mean value of incubation time is about 12.6 days, and the standard deviation is about 6.1 days. The incubation time of 95% of patients was within 24 days. Some patients have a very long incubation time according to the excess function. The incubation time was not related to age and gender but related to the suspected contact modes. Conclusions. The mean value of incubation time is consistent with the actual situation. The above results are a reasonable explanation for the phenomenon of super-long incubation time in some patients and the development trend of epidemic situations. [ FROM AUTHOR] Copyright of Discrete Dynamics in Nature & Society is the property of Hindawi Limited and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

2.
J Immunol ; 2022 May 23.
Article in English | MEDLINE | ID: covidwho-1863025

ABSTRACT

The adaptive immune receptor repertoire consists of the entire set of an individual's BCRs and TCRs and is believed to contain a record of prior immune responses and the potential for future immunity. Analyses of TCR repertoires via deep learning (DL) methods have successfully diagnosed cancers and infectious diseases, including coronavirus disease 2019. However, few studies have used DL to analyze BCR repertoires. In this study, we collected IgG H chain Ab repertoires from 276 healthy control subjects and 326 patients with various infections. We then extracted a comprehensive feature set consisting of 10 subsets of repertoire-level features and 160 sequence-level features and tested whether these features can distinguish between infected individuals and healthy control subjects. Finally, we developed an ensemble DL model, namely, DL method for infection diagnosis (https://github.com/chenyuan0510/DeepID), and used this model to differentiate between the infected and healthy individuals. Four subsets of repertoire-level features and four sequence-level features were selected because of their excellent predictive performance. The DL method for infection diagnosis outperformed traditional machine learning methods in distinguishing between healthy and infected samples (area under the curve = 0.9883) and achieved a multiclassification accuracy of 0.9104. We also observed differences between the healthy and infected groups in V genes usage, clonal expansion, the complexity of reads within clone, the physical properties in the α region, and the local flexibility of the CDR3 amino acid sequence. Our results suggest that the Ab repertoire is a promising biomarker for the diagnosis of various infections.

3.
Int J Gen Med ; 15: 4285-4301, 2022.
Article in English | MEDLINE | ID: covidwho-1817654

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) greatly affects cancer patients, especially those with lung cancer. This study aimed to identify potential drug targets for lung adenocarcinoma (LUAD) patients with COVID-19. Methods: LUAD samples were obtained from public databases. Differentially expressed genes (DEGs) related to COVID-19 were screened. Protein-protein interactions among COVID-19-related genes, the traditional Chinese medicine (TCM) and TCM target genes were analyzed by CytoScape. The correlation between tumor microenvironment and COVID-19 target genes were assessed by Pearson correlation analysis. Unsupervised consensus clustering was conducted to categorize molecular subtypes. Results: We filtered 26 COVID-19 target genes related to TCM for LUAD. Interleukin (IL)-17 signaling pathway and tumor necrosis factor (TNF) signaling pathway were significantly enriched in these 26 genes. A strong correlation was found between COVID-19 target genes and tumor microenvironment (TME), cell death. Importantly, interleukin-1beta (IL1B) was identified as a core gene in the protein-protein interactions (PPI) network. Based on the 26 target genes, two molecular subtypes showing distinct overall survival, TME and response to target therapy were developed. Conclusions: This study explored 26 COVID-19 target genes, which could serve as potential therapeutic drug targets for LUAD. IL1B was verified as a critical target for developing new molecular drugs. Furthermore, two novel molecular subtypes showed the potential to guide personalized therapies in clinical practice.

4.
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences ; 49(2):245-248, 2020.
Article in Chinese | EuropePMC | ID: covidwho-1772476

ABSTRACT

目的 探讨亟待进行肿瘤根治术的患者合并2019冠状病毒病(COVID-19)后如何选择手术治疗时机。 方法 详细分析1例乙状结肠癌合并COVID-19患者的治疗过程,以及该患者在病毒两次转阴后进行根治性手术后的恢复情况。 结果 患者术后恢复良好,炎症指标、发热等临床表现改善,肺部病灶也维持稳定。 结论 对于亟待进行肿瘤根治术且合并COVID-19的患者,在符合病毒核酸检测两次阴性之后进行肿瘤根治术是可行的。

5.
J Cell Mol Med ; 26(7): 1979-1993, 2022 04.
Article in English | MEDLINE | ID: covidwho-1774827

ABSTRACT

Acute kidney injury (AKI) is a substantial worldwide public health concern with no specific and effective therapies in clinic. NAD+ is a pivotal determinant of cellular energy metabolism involved in the progression of AKI; however, its mechanism in kidney injury remains poorly understood. Sirtuin 1 (SIRT1) is an NAD+ -dependent deacetylase associated with renal protection and acute stress resistance. In this study, we have investigated the role of NAD+ in AKI and the potential mechanism(s) involved in its renoprotective effect. NAD+ was notably decreased and negatively correlated with kidney dysfunction in AKI, restoring NAD+ with NMN significantly ameliorates LPS-induced oxidative stress and apoptosis and attenuates renal damage. We also found that the protection of NAD+ is associated with SIRT1 expressions and performs in a SIRT1-dependent manner. Inhibition of SIRT1 blunted the protective effect of NAD+ and up-regulated the activity of glycogen synthase kinase-3ß (GSK-3ß) that was concomitant with mitigated Nrf2 nuclear accumulation, thereby exacerbates AKI. These findings suggest that NAD+ /SIRT1/GSK-3ß/Nrf2 axis is an important mechanism that can protect against AKI which might be a potential therapeutic target for the treatment of AKI.


Subject(s)
Acute Kidney Injury , Glycogen Synthase Kinase 3 beta , NAD , NF-E2-Related Factor 2 , Sirtuin 1 , Acute Kidney Injury/metabolism , Endotoxins , Glycogen Synthase Kinase 3 beta/metabolism , Humans , NAD/metabolism , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Sirtuin 1/genetics , Sirtuin 1/metabolism
6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325218

ABSTRACT

SARS-CoV-2 can infect many domestic animals, including dogs. Herein, we show that dog angiotensin converting enzyme 2 (dACE2) can bind to SARS-CoV-2 spike (S) protein receptor binding region (RBD), and that both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells. we solved the crystal structure of RBD in complex with dACE2 and found that the total numbers of contact residues, contact atoms, hydrogen bonds and salt bridges at the binding interface in this complex are slightly fewer than those in the complex of the RBD and human ACE2 (hACE2). This result is consistent with the fact that the binding affinity of RBD to dACE2 is lower than that to hACE2. We further show that a few important mutations in the RBD binding interface play a pivotal role in the binding affinity of RBD to both dACE2 and hACE2, and need intense monitoring and controlling.

8.
Sci Rep ; 11(1): 23223, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1553757

ABSTRACT

Low pathogenic avian influenza viruses (LPAIVs) have been widespread in poultry and wild birds throughout the world for many decades. LPAIV infections are usually asymptomatic or cause subclinical symptoms. However, the genetic reassortment of LPAIVs may generate novel viruses with increased virulence and cross-species transmission, posing potential risks to public health. To evaluate the epidemic potential and infection landscape of LPAIVs in Guangxi Province, China, we collected and analyzed throat and cloacal swab samples from chickens, ducks and geese from the live poultry markets on a regular basis from 2016 to 2019. Among the 7,567 samples, 974 (12.87%) were LPAIVs-positive, with 890 single and 84 mixed infections. Higher yearly isolation rates were observed in 2017 and 2018. Additionally, geese had the highest isolation rate, followed by ducks and chickens. Seasonally, spring had the highest isolation rate. Subtype H3, H4, H6 and H9 viruses were detected over prolonged periods, while H1 and H11 viruses were detected transiently. The predominant subtypes in chickens, ducks and geese were H9, H3, and H6, respectively. The 84 mixed infection samples contained 22 combinations. Most mixed infections involved two subtypes, with H3 + H4 as the most common combination. Our study provides important epidemiological data regarding the isolation rates, distributions of prevalent subtypes and mixed infections of LPAIVs. These results will improve our knowledge and ability to control epidemics, guide disease management strategies and provide early awareness of newly emerged AIV reassortants with pandemic potential.


Subject(s)
Influenza A virus/isolation & purification , Influenza in Birds/epidemiology , Influenza in Birds/virology , Poultry/virology , Animals , Chickens/virology , China/epidemiology , Ducks/virology , Epidemiological Monitoring , Geese/virology , Influenza A virus/genetics
9.
Front Immunol ; 12: 717496, 2021.
Article in English | MEDLINE | ID: covidwho-1512035

ABSTRACT

The antibody repertoire is a critical component of the adaptive immune system and is believed to reflect an individual's immune history and current immune status. Delineating the antibody repertoire has advanced our understanding of humoral immunity, facilitated antibody discovery, and showed great potential for improving the diagnosis and treatment of disease. However, no tool to date has effectively integrated big Rep-seq data and prior knowledge of functional antibodies to elucidate the remarkably diverse antibody repertoire. We developed a Rep-seq dataset Analysis Platform with an Integrated antibody Database (RAPID; https://rapid.zzhlab.org/), a free and web-based tool that allows researchers to process and analyse Rep-seq datasets. RAPID consolidates 521 WHO-recognized therapeutic antibodies, 88,059 antigen- or disease-specific antibodies, and 306 million clones extracted from 2,449 human IGH Rep-seq datasets generated from individuals with 29 different health conditions. RAPID also integrates a standardized Rep-seq dataset analysis pipeline to enable users to upload and analyse their datasets. In the process, users can also select set of existing repertoires for comparison. RAPID automatically annotates clones based on integrated therapeutic and known antibodies, and users can easily query antibodies or repertoires based on sequence or optional keywords. With its powerful analysis functions and rich set of antibody and antibody repertoire information, RAPID will benefit researchers in adaptive immune studies.


Subject(s)
Antibodies/genetics , Computational Biology/methods , Databases, Genetic , Humans , Software , Web Browser
10.
Nat Commun ; 12(1): 6103, 2021 10 20.
Article in English | MEDLINE | ID: covidwho-1475296

ABSTRACT

Multiple SARS-CoV-2 variants of concern (VOCs) have been emerging and some have been linked to an increase in case numbers globally. However, there is yet a lack of understanding of the molecular basis for the interactions between the human ACE2 (hACE2) receptor and these VOCs. Here we examined several VOCs including Alpha, Beta, and Gamma, and demonstrate that five variants receptor-binding domain (RBD) increased binding affinity for hACE2, and four variants pseudoviruses increased entry into susceptible cells. Crystal structures of hACE2-RBD complexes help identify the key residues facilitating changes in hACE2 binding affinity. Additionally, soluble hACE2 protein efficiently prevent most of the variants pseudoviruses. Our findings provide important molecular information and may help the development of novel therapeutic and prophylactic agents targeting these emerging mutants.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/virology , Protein Interaction Domains and Motifs/genetics , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Amino Acid Sequence , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/isolation & purification , Angiotensin-Converting Enzyme 2/ultrastructure , Animals , Cell Line, Tumor , Crystallography, X-Ray , HEK293 Cells , Humans , Molecular Dynamics Simulation , Mutation , Recombinant Proteins/genetics , Recombinant Proteins/isolation & purification , Recombinant Proteins/metabolism , Recombinant Proteins/ultrastructure , SARS-CoV-2/genetics , Sf9 Cells , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/isolation & purification , Spike Glycoprotein, Coronavirus/ultrastructure , Spodoptera , Surface Plasmon Resonance , Virus Attachment , Virus Internalization
11.
Nat Commun ; 12(1): 4195, 2021 07 07.
Article in English | MEDLINE | ID: covidwho-1301166

ABSTRACT

SARS-CoV-2 can infect many domestic animals, including dogs. Herein, we show that dog angiotensin-converting enzyme 2 (dACE2) can bind to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD), and that both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells. We solved the crystal structure of RBD in complex with dACE2 and found that the total number of contact residues, contact atoms, hydrogen bonds and salt bridges at the binding interface in this complex are slightly fewer than those in the complex of the RBD and human ACE2 (hACE2). This result is consistent with the fact that the binding affinity of RBD to dACE2 is lower than that of hACE2. We further show that a few important mutations in the RBD binding interface play a pivotal role in the binding affinity of RBD to both dACE2 and hACE2. Our work reveals a molecular basis for cross-species transmission and potential animal spread of SARS-CoV-2, and provides new clues to block the potential transmission chains of this virus.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , SARS-CoV-2/metabolism , Angiotensin-Converting Enzyme 2/chemistry , Animals , Binding Sites , Cell Line , Cricetinae , Crystallography, X-Ray , Dogs , HeLa Cells , Humans , Mutation , Protein Binding , Protein Domains , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization
12.
Cell ; 184(13): 3438-3451.e10, 2021 06 24.
Article in English | MEDLINE | ID: covidwho-1275185

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading worldwide, causing a global pandemic. Bat-origin RaTG13 is currently the most phylogenetically related virus. Here we obtained the complex structure of the RaTG13 receptor binding domain (RBD) with human ACE2 (hACE2) and evaluated binding of RaTG13 RBD to 24 additional ACE2 orthologs. By substituting residues in the RaTG13 RBD with their counterparts in the SARS-CoV-2 RBD, we found that residue 501, the major position found in variants of concern (VOCs) 501Y.V1/V2/V3, plays a key role in determining the potential host range of RaTG13. We also found that SARS-CoV-2 could induce strong cross-reactive antibodies to RaTG13 and identified a SARS-CoV-2 monoclonal antibody (mAb), CB6, that could cross-neutralize RaTG13 pseudovirus. These results elucidate the receptor binding and host adaption mechanisms of RaTG13 and emphasize the importance of continuous surveillance of coronaviruses (CoVs) carried by animal reservoirs to prevent another spillover of CoVs.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Binding Sites/physiology , COVID-19/metabolism , Chiroptera/virology , SARS-CoV-2/pathogenicity , Amino Acid Sequence , Animals , Antibodies, Monoclonal/immunology , COVID-19/immunology , Chiroptera/immunology , Chiroptera/metabolism , Host Specificity/immunology , Humans , Phylogeny , Protein Binding/physiology , Receptors, Virus/metabolism , SARS-CoV-2/immunology , Sequence Alignment
13.
EMBO J ; 40(16): e107786, 2021 08 16.
Article in English | MEDLINE | ID: covidwho-1239217

ABSTRACT

Pangolins have been suggested as potential reservoir of zoonotic viruses, including SARS-CoV-2 causing the global COVID-19 outbreak. Here, we study the binding of two SARS-CoV-2-like viruses isolated from pangolins, GX/P2V/2017 and GD/1/2019, to human angiotensin-converting enzyme 2 (hACE2), the receptor of SARS-CoV-2. We find that the spike protein receptor-binding domain (RBD) of pangolin CoVs binds to hACE2 as efficiently as the SARS-CoV-2 RBD in vitro. Furthermore, incorporation of pangolin CoV RBDs allows entry of pseudotyped VSV particles into hACE2-expressing cells. A screen for binding of pangolin CoV RBDs to ACE2 orthologs from various species suggests a broader host range than that of SARS-CoV-2. Additionally, cryo-EM structures of GX/P2V/2017 and GD/1/2019 RBDs in complex with hACE2 show their molecular binding in modes similar to SARS-CoV-2 RBD. Introducing the Q498H substitution found in pangolin CoVs into the SARS-CoV-2 RBD expands its binding capacity to ACE2 homologs of mouse, rat, and European hedgehog. These findings suggest that these two pangolin CoVs may infect humans, highlighting the necessity of further surveillance of pangolin CoVs.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Betacoronavirus/physiology , Pangolins/virology , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Amino Acid Substitution , Angiotensin-Converting Enzyme 2/chemistry , Animals , Binding Sites , HEK293 Cells , Hedgehogs/virology , Host Specificity , Humans , Mice , Models, Molecular , Phylogeny , Protein Binding , Protein Conformation , Rats , Spike Glycoprotein, Coronavirus/genetics , Virus Internalization
14.
mBio ; 12(2)2021 04 27.
Article in English | MEDLINE | ID: covidwho-1206004

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affected over 120 million people and killed over 2.7 million individuals by March 2021. While acute and intermediate interactions between SARS-CoV-2 and the immune system have been studied extensively, long-term impacts on the cellular immune system remain to be analyzed. Here, we comprehensively characterized immunological changes in peripheral blood mononuclear cells in 49 COVID-19-convalescent individuals (CI) in comparison to 27 matched SARS-CoV-2-unexposed individuals (UI). Despite recovery from the disease for more than 2 months, CI showed significant decreases in frequencies of invariant NKT and NKT-like cells compared to UI. Concomitant with the decrease in NKT-like cells, an increase in the percentage of annexin V and 7-aminoactinomycin D (7-AAD) double-positive NKT-like cells was detected, suggesting that the reduction in NKT-like cells results from cell death months after recovery. Significant increases in regulatory T cell frequencies and TIM-3 expression on CD4 and CD8 T cells were also observed in CI, while the cytotoxic potential of T cells and NKT-like cells, defined by granzyme B (GzmB) expression, was significantly diminished. However, both CD4 and CD8 T cells of CI showed increased Ki67 expression and were fully able to proliferate and produce effector cytokines upon T cell receptor (TCR) stimulation. Collectively, we provide a comprehensive characterization of immune signatures in patients recovering from SARS-CoV-2 infection, suggesting that the cellular immune system of COVID-19 patients is still under a sustained influence even months after the recovery from disease.IMPORTANCE Wuhan was the very first city hit by SARS-CoV-2. Accordingly, the patients who experienced the longest phase of convalescence following COVID-19 reside here. This enabled us to investigate the "immunological scar" left by SARS-CoV-2 on cellular immunity after recovery from the disease. In this study, we characterized the long-term impact of SARS-CoV-2 infection on the immune system and provide a comprehensive picture of cellular immunity of a convalescent COVID-19 patient cohort with the longest recovery time. We revealed that the cellular immune system of COVID-19 patients is still under a sustained influence even months after the recovery from disease; in particular, a profound NKT cell impairment was found in the convalescent phase of COVID-19.


Subject(s)
COVID-19/immunology , Convalescence , Immunity, Cellular , Natural Killer T-Cells/immunology , Adult , Apoptosis , COVID-19/diagnosis , Cohort Studies , Cytokines/immunology , Cytotoxicity, Immunologic , Female , Humans , Leukocytes, Mononuclear/immunology , Male , Middle Aged , Phenotype , SARS-CoV-2/immunology , T-Lymphocyte Subsets/immunology
15.
Proc Natl Acad Sci U S A ; 118(1)2021 01 05.
Article in English | MEDLINE | ID: covidwho-1066044

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global health. Although varied SARS-CoV-2-related coronaviruses have been isolated from bats and SARS-CoV-2 may infect bat, the structural basis for SARS-CoV-2 to utilize the human receptor counterpart bat angiotensin-converting enzyme 2 (bACE2) for virus infection remains less understood. Here, we report that the SARS-CoV-2 spike protein receptor binding domain (RBD) could bind to bACE2 from Rhinolophus macrotis (bACE2-Rm) with substantially lower affinity compared with that to the human ACE2 (hACE2), and its infectivity to host cells expressing bACE2-Rm was confirmed with pseudotyped SARS-CoV-2 virus and SARS-CoV-2 wild virus. The structure of the SARS-CoV-2 RBD with the bACE2-Rm complex was determined, revealing a binding mode similar to that of hACE2. The analysis of binding details between SARS-CoV-2 RBD and bACE2-Rm revealed that the interacting network involving Y41 and E42 of bACE2-Rm showed substantial differences with that to hACE2. Bats have extensive species diversity and the residues for RBD binding in bACE2 receptor varied substantially among different bat species. Notably, the Y41H mutant, which exists in many bats, attenuates the binding capacity of bACE2-Rm, indicating the central roles of Y41 in the interaction network. These findings would benefit our understanding of the potential infection of SARS-CoV-2 in varied species of bats.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19/genetics , COVID-19/metabolism , Chiroptera , SARS-CoV-2 , Amino Acid Substitution , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/epidemiology , Chiroptera/genetics , Chiroptera/metabolism , Chiroptera/virology , HEK293 Cells , Humans , Mutation, Missense , Pandemics , Protein Binding , Protein Domains , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , Species Specificity
16.
Proc Natl Acad Sci U S A ; 118(1)2021 01 05.
Article in English | MEDLINE | ID: covidwho-990135

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global health. Although varied SARS-CoV-2-related coronaviruses have been isolated from bats and SARS-CoV-2 may infect bat, the structural basis for SARS-CoV-2 to utilize the human receptor counterpart bat angiotensin-converting enzyme 2 (bACE2) for virus infection remains less understood. Here, we report that the SARS-CoV-2 spike protein receptor binding domain (RBD) could bind to bACE2 from Rhinolophus macrotis (bACE2-Rm) with substantially lower affinity compared with that to the human ACE2 (hACE2), and its infectivity to host cells expressing bACE2-Rm was confirmed with pseudotyped SARS-CoV-2 virus and SARS-CoV-2 wild virus. The structure of the SARS-CoV-2 RBD with the bACE2-Rm complex was determined, revealing a binding mode similar to that of hACE2. The analysis of binding details between SARS-CoV-2 RBD and bACE2-Rm revealed that the interacting network involving Y41 and E42 of bACE2-Rm showed substantial differences with that to hACE2. Bats have extensive species diversity and the residues for RBD binding in bACE2 receptor varied substantially among different bat species. Notably, the Y41H mutant, which exists in many bats, attenuates the binding capacity of bACE2-Rm, indicating the central roles of Y41 in the interaction network. These findings would benefit our understanding of the potential infection of SARS-CoV-2 in varied species of bats.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19/genetics , COVID-19/metabolism , Chiroptera , SARS-CoV-2 , Amino Acid Substitution , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/epidemiology , Chiroptera/genetics , Chiroptera/metabolism , Chiroptera/virology , HEK293 Cells , Humans , Mutation, Missense , Pandemics , Protein Binding , Protein Domains , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , Species Specificity
17.
Cell Discov ; 6: 68, 2020.
Article in English | MEDLINE | ID: covidwho-817184

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the recent pandemic COVID-19, is reported to have originated from bats, with its intermediate host unknown to date. Here, we screened 26 animal counterparts of the human ACE2 (hACE2), the receptor for SARS-CoV-2 and SARS-CoV, and found that the ACE2s from various species, including pets, domestic animals and multiple wild animals, could bind to SARS-CoV-2 receptor binding domain (RBD) and facilitate the transduction of SARS-CoV-2 pseudovirus. Comparing to SARS-CoV-2, SARS-CoV seems to have a slightly wider range in choosing its receptor. We further resolved the cryo-electron microscopy (cryo-EM) structure of the cat ACE2 (cACE2) in complex with the SARS-CoV-2 RBD at a resolution of 3 Å, revealing similar binding mode as hACE2 to the SARS-CoV-2 RBD. These results shed light on pursuing the intermediate host of SARS-CoV-2 and highlight the necessity of monitoring susceptible hosts to prevent further outbreaks.

18.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(2): 245-248, 2020 05 25.
Article in Chinese | MEDLINE | ID: covidwho-808360

ABSTRACT

OBJECTIVE: To explore the feasibility of surgical treatment for cancer patients complicated with corona virus disease 2019 (COVID-19). METHODS: The management and clinical outcome of a sigmoid cancer patient with COVID-19 were analyzed. RESULTS: The inflammation indicators and fever of this patient were effectively controlled and the lung lesions remained stable after active anti-viral treatment, then the radical colorectomy was performed after the viral negative conversion for twice. CONCLUSIONS: The case indicates that it may feasible to undergo radical tumor surgery for cancer patients with COVID-19 after the virus nucleic acid testing turns negative and more studies are needed to confirm this conclusion.


Subject(s)
Colonic Neoplasms/surgery , Coronavirus Infections , Pandemics , Pneumonia, Viral , Antiviral Agents/therapeutic use , Betacoronavirus , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Colonic Neoplasms/complications , Colonic Neoplasms/virology , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Fever , Humans , Nucleic Acid Amplification Techniques , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , SARS-CoV-2
19.
Curr Med Sci ; 40(4): 618-624, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-695581

ABSTRACT

The COVID-19 pandemic caused by SARS-CoV2 is characterized by a remarkable variation in clinical severity ranging from a mild illness to a fatal multi-organ disease. Understanding the dysregulated human immune responses in the fatal subjects is critical for management of COVID-19 patients and the pandemic. In this study, we examined the immune cell compositions in the lung tissues and hilar lymph nodes using immunohistochemistry on 6 deceased COVID-19 patients and 4 focal organizing pneumonia (FOP) patients who underwent lung surgery and served as controls. We found a dominant presence of macrophages and a general deficiency of T cells and B cells in the lung tissues from deceased COVID-19 patients. In contrast to the FOP patients, Tfh cells and germinal center formation were largely absent in the draining hilar lymph nodes in the deceased COVID-19 patients. This was correlated with reduced IgM and IgG levels compared to convalescent COVID-19 patients. In summary, our data highlight a defect of germinal center structure in deceased COVID-19 patients leading to an impaired humoral immunity. Understanding the mechanisms of this deficiency will be one of the key points for the management of this epidemic.


Subject(s)
Betacoronavirus , Coronavirus Infections/immunology , Germinal Center/immunology , Pneumonia, Viral/immunology , T-Lymphocytes, Helper-Inducer/immunology , Adaptive Immunity , Aged , Aged, 80 and over , COVID-19 , Case-Control Studies , China/epidemiology , Coronavirus Infections/mortality , Coronavirus Infections/pathology , Fatal Outcome , Female , Germinal Center/pathology , Humans , Lymphopenia/immunology , Lymphopenia/mortality , Lymphopenia/pathology , Macrophages/immunology , Macrophages/pathology , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/pathology , SARS-CoV-2 , T-Lymphocytes, Helper-Inducer/pathology
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