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2.
Medicine (Baltimore) ; 100(14): e24904, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33832070

RESUMO

BACKGROUND: The role of the HLA-DRB1 and HLA-DQB1 genes in the antibody response to hepatitis B (HB) vaccine has been well established; however, the involvement of the HLA-DPB1 allele in the HB vaccine immune response remained to be clarified by a systematic review. METHODS: A meta-analysis was performed in which databases were searched for relevant studies published in English or Chinese up until June 1, 2020. Six studies were identified and a total of 10 alleles were processed into statistical processing in this meta-analysis. RESULTS: Three thousand one hundred forty four subjects (including 2477 responders and 667 non-responders) were included in this research. Alleles HLA-DPB1∗02:02, DPB1∗03:01, DPB1∗04:01, DPB1∗04:02, and DPB1∗14:01 were found to be associated with a significant increase in the antibody response to HB vaccine, and their pooled odds ratios (ORs) were 4.53, 1.57, 3.33, 4.20, and 1.79, respectively; whereas DPB1∗05:01 (OR = 0.73) showed the opposite correlation. CONCLUSIONS: These findings suggested that specific HLA-DPB1 alleles are associated with the antibody response to HB vaccine.

3.
Int J Mol Sci ; 22(7)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33805879

RESUMO

Auxin response factors (ARFs) play important roles in various plant physiological processes; however, knowledge of the exact role of ARFs in plant responses to water deficit is limited. In this study, SlARF4, a member of the ARF family, was functionally characterized under water deficit. Real-time fluorescence quantitative polymerase chain reaction (PCR) and ß-glucuronidase (GUS) staining showed that water deficit and abscisic acid (ABA) treatment reduced the expression of SlARF4. SlARF4 was expressed in the vascular bundles and guard cells of tomato stomata. Loss of function of SlARF4 (arf4) by using Clustered Regularly Interspaced Short Palindromic Repeats/Cas 9 (CRISPR/Cas 9) technology enhanced plant resistance to water stress and rehydration ability. The arf4 mutant plants exhibited curly leaves and a thick stem. Malondialdehyde content was significantly lower in arf4 mutants than in wildtype plants under water stress; furthermore, arf4 mutants showed higher content of antioxidant substances, superoxide dismutase, actual photochemical efficiency of photosystem II (PSII), and catalase activities. Stomatal and vascular bundle morphology was changed in arf4 mutants. We identified 628 differentially expressed genes specifically expressed under water deficit in arf4 mutants; six of these genes, including ABA signaling pathway-related genes, were differentially expressed between the wildtype and arf4 mutants under water deficit and unlimited water supply. Auxin responsive element (AuxRE) elements were found in these genes' promoters indicating that SlARF4 participates in ABA signaling pathways by regulating the expression of SlABI5/ABF and SCL3, thereby influencing stomatal morphology and vascular bundle development and ultimately improving plant resistance to water deficit.

4.
Immunogenetics ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33710355

RESUMO

Hepatitis B virus (HBV) affects approximately 68 million people in China, and 10-15% of adults infected with HBV develop chronic hepatitis B, liver cirrhosis, liver failure or hepatocellular carcinoma (HCC). HLA-DPB1 gene polymorphism and expression have been shown to be associated with HBV infection susceptibility and spontaneous clearance. The aim of this study is to evaluate the role of HLA-DPB1 gene polymorphism in HBV infection. HLA-DPB1 and rs9277535 polymorphisms were investigated in 259 patients with HBV infection and 442 healthy controls (HCs) using sequence-based typing. The mRNA of HLA-DPB1 was measured by real-time polymerase chain reaction. HLA-DPB1 genes and rs9277535 polymorphisms were all associated with HBV infection in the Sichuan Han population. rs9277535A and HLA-DPB1*04:02 played a protective role against HBV infection. rs9277535G and DPB1*05:01 were associated with susceptibility to HBV infection. rs9277535GG had significantly higher HLA-DPB1 mRNA expression in the HBV infection group compared with the HC group. HLA-DPB1*05:01 and HLA-DPB1*21:01 had significantly lower mRNA expression in the HBV infection group compared with the HC group. The meta-analysis revealed that HLA-DPB1*02:01, HLA-DPB1*02:02, HAL-DPB1*04:01 and HLA-DPB1*04:02 protected against HBV infection, while HLA-DPB1*05:01, HLA-DPB1*09:01, and HLA-DPB1*13:01 were risk factors for susceptibility to HBV infection. HLA-DPB1*02:01, HLA-DPB1*02:02, and HLA-DPB1*04:01 were associated with HBV spontaneous clearance, while HLA-DPB1*05:01 was associated with chronic HBV infection. HLA-DPB1 alleles and rs9277535 have a major effect on the risk of HBV infection, and HBV infection is associated with lower HLA-DPB1 expression. HLA-DPB1 alleles have an important role in HBV susceptibility and spontaneous clearance.

5.
Food Res Int ; 141: 110162, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33642022

RESUMO

The impact of lipid content of excipient nanoemulsions on the bioavailability of carotenoids from spinach was assessed using a combination of in vitro and in vivo digestion models. Alterations in the particle size, charge, microstructure, and lipid digestion were monitored as the spinach-nanoemulsion mixtures passed through the digestive tract. There was an increase in both bioaccessibility (19.2% > 14.4% > 7.5% > 3.1%) and bioavailability (106.7 > 39.6 ≈ 35.3 > 15.0 ng/mL) of carotenoids with increasing lipid content (1.0, 0.6, 0.2, 0 g), which attributed to higher transfer efficiency of the carotenoids from spinach to fat droplets and mixed micelles in increasing lipid content. The polarity of carotenoids also had an important impact: the bioavailability of lutein was significantly higher than that of ß-carotene. Our findings show the importance of selecting an appropriate lipid content of reduced-fat emulsion-based foods to enhance the oral bioavailability of co-ingested hydrophobic nutraceuticals.

6.
Immunology ; 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33738807

RESUMO

In contrast to humans or rabbits, in which maternal IgG is transmitted to offspring prenatally via the placenta or the yolk sac, large domestic animals such as pigs, cows and sheep transmit IgG exclusively through colostrum feeding after delivery. The extremely high IgG content in colostrum is absorbed by newborns via the small intestine. Although it is widely accepted that the neonatal Fc receptor, FcRn, is the receptor mediating IgG transfer across both the placenta and small intestine, it remains unclear whether FcRn also mediates serum IgG transfer across the mammary barrier to colostrum/milk, especially in large domestic animals. In this study, using a FcRn knockout pig model generated with a CRISPR-Cas9 based approach, we clearly demonstrate that FcRn is not responsible for the IgG transfer from serum to colostrum in pigs, although like in other mammals, it is involved in IgG homeostasis and mediates IgG absorption in the small intestine of newborns.

7.
Invest Ophthalmol Vis Sci ; 62(3): 37, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33764399

RESUMO

Purpose: This study examined the role of the CSF1/CSF1Raxis in the crosstalk between choroidal vascular endothelial cells (CVECs) and macrophages during the formation of choroidal neovascularization (CNV). Methods: Quantitative reverse transcriptase (QRT)-PCR, Western blot and ELISA measured the production and release of CSF1 from human choroidal vascular endothelial cells (HCVECs) under hypoxic conditions. Western blot detected CSF1 released from HCVECs under hypoxic conditions that activated the PI3K/AKT/FOXO1 axis in human macrophages via binding to CSF1R. Transwell migration assay, qRT-PCR, and Western blot detected the effect of CSF1 released from HCVECs on macrophage migration and M2 polarization via the CSF1R/PI3K/AKT/FOXO1 pathway. Incorporation of 5-ethynyl-20-deoxyuridine, transwell migration, and tube formation assays detected the effects of CSF1/CSF1R on the behaviors of HCVECs. Fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), and immunofluorescence detected the effect of blockade of CSF1/CSF1R on mouse laser-induced CNV. Color fundus photograph, ICGA, and FFA detected CNV lesions in neovascular AMD (nAMD) patients. ELISA detected CSF1 and CSF1R in the aqueous humor of age-related cataract and nAMD patients. Results: CSF1 released from HCVECs under hypoxic conditions activated the PI3K/AKT/FOXO1 axis in human macrophages via binding to CSF1R, promoting macrophage migration and M2 polarization via up-regulation of the CSF1R/PI3K/AKT/FOXO1 pathway. Human macrophages promoted the proliferation, migration, and tube formation of HCVECs in a CSF1/CSFR1-dependent manner under hypoxic conditions. CSF1/CSF1R blockade ameliorated the formation of mouse laser-induced CNV. CSF1 and CSF1R were increased in the aqueous humor of nAMD patients. Conclusions: Our results affirmed the crucial role of CSF1/CSF1R in boosting the formation of CNV and offered potential molecular targets for the treatment of nAMD.

8.
Sci Total Environ ; 774: 145180, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33609847

RESUMO

The growth of the economy in the tropics is faster than that in the rest of the world. However, whether this growth can have impacts on the environmental quality in the tropics is still a question. Here, we first introduce the terrestrial carbon sequestration capacity as an environmental indicator and then investigate the relationships between gross domestic product per capita, sectoral economies, and the terrestrial carbon sequestration capacity for different income countries in the tropics from 1995 to 2018. By using panel models, we find that there exists a significantly negative effect of the growth of gross domestic product per capita on terrestrial carbon sequestration capacity in the full panel and at low-income and lower middle-income levels but not at the upper middle-income level. The sectoral economies have different effects on the terrestrial carbon sequestration capacity at different income levels. Interestingly, the industrial sector dominates the degradation of the terrestrial carbon sequestration capacity in the lower middle-income countries; the agricultural sector exerts a significantly negative impact on the terrestrial carbon sequestration capacity at the low-income and upper middle-income levels, but largely offset by the growth of the service sector. These findings suggest that the balance between economic development and the natural environment is required for economic sustainability in the tropics.

9.
Stem Cell Reports ; 16(3): 493-504, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33626333

RESUMO

Enteroviruses, such as EV-A71 and CVA16, mainly infect the human gastrointestinal tract. Human coronaviruses, including SARS-CoV and SARS-CoV-2, have been variably associated with gastrointestinal symptoms. We aimed to optimize the human intestinal organoids and hypothesize that these optimized intestinal organoids can recapitulate enteric infections of enterovirus and coronavirus. We demonstrate that the optimized human intestinal organoids enable better simulation of the native human intestinal epithelium, and that they are significantly more susceptible to EV-A71 than CVA16. Higher replication of EV-A71 than CVA16 in the intestinal organoids triggers a more vigorous cellular response. However, SARS-CoV and SARS-CoV-2 exhibit distinct dynamics of virus-host interaction; more robust propagation of SARS-CoV triggers minimal cellular response, whereas, SARS-CoV-2 exhibits lower replication capacity but elicits a moderate cellular response. Taken together, the disparate profile of the virus-host interaction of enteroviruses and coronaviruses in human intestinal organoids may unravel the cellular basis of the distinct pathogenicity of these viral pathogens.


Assuntos
/virologia , Enterovirus Humano A/patogenicidade , Infecções por Enterovirus/virologia , Intestinos/virologia , Organoides/virologia , /patogenicidade , Animais , Linhagem Celular , Chlorocebus aethiops , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Mucosa Intestinal/virologia , Células Vero , Replicação Viral/fisiologia
10.
Emerg Microbes Infect ; 10(1): 342-355, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33555988

RESUMO

The current study aims to develop a safe and highly immunogenic COVID-19 vaccine. The novel combination of a DNA vaccine encoding the full-length Spike (S) protein of SARS-CoV-2 and a recombinant S1 protein vaccine induced high level neutralizing antibody and T cell immune responses in both small and large animal models. More significantly, the co-delivery of DNA and protein components at the same time elicited full protection against intratracheal challenge of SARS-CoV-2 viruses in immunized rhesus macaques. As both DNA and protein vaccines have been proven safe in previous human studies, and DNA vaccines are capable of eliciting germinal center B cell development, which is critical for high-affinity memory B cell responses, the DNA and protein co-delivery vaccine approach has great potential to serve as a safe and effective approach to develop COVID-19 vaccines that provide long-term protection.


Assuntos
/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas de DNA/imunologia , Vacinas de Subunidades/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Linhagem Celular , DNA/imunologia , Células HEK293 , Humanos , Contagem de Linfócitos , Macaca mulatta , Camundongos , Camundongos Endogâmicos C57BL , Plasmídeos/genética , Coelhos , Proteínas Recombinantes/imunologia , /imunologia , Linfócitos T/imunologia
11.
Nanoscale ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33527935

RESUMO

Topological nodal-line semimetals, as a type of exotic quantum electronic state, have drawn considerable research interest recently. In this work, we propose a new two-dimensional covalent-organic Cr2N6C3 monolayer (ML) material, which has a combined honeycomb and effective Kagome lattice and has various half-metallic nodal loops (HMNLs). First-principles calculations show that the Cr2N6C3 ML is dynamically and thermally stable and has an out-of-plane ferromagnetic order. Remarkably, various nodal loops, including types I-III, are found coexisting in the material, all of which are rare half-metallic states. The obtained HMNLs, simultaneously possessing the merits of spintronics and semimetals, are robust against spin-orbit coupling and biaxial strain. A topological phase transition, characterized by loop-winding indexes, can be induced in the ML by applying uniaxial strain. Tight-binding model calculations show that the obtained HMNLs originate primarily from the band inversion between Cr dx2-y2/xy and N pz orbitals, accommodated on the honeycomb and Kagome sublattices, respectively. The various predicted HMNLs and topological behaviors mean that the Cr2N6C3 MLs have promisingly versatile applications in future low-power-consuming spintronics and electronics.

12.
Org Biomol Chem ; 19(8): 1738-1743, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33543173

RESUMO

An efficient nano-Cu2O-catalyzed cascade multicomponent reaction of 2-halobenzoic acids and trimethylsilyl cyanide with diverse amines was developed using water as a solvent, affording versatile N-substituted phthalimide derivatives in moderate to excellent yields. This novel strategy features carbon monoxide gas-free, environmentally benign, one-pot multistep transformation, commercially available reagents, a cheap catalyst without any additives, wide functional group tolerance, and operational convenience.

13.
Inorg Chem ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33434017

RESUMO

Based on first-principles calculations with the DFT + U method, the couplings of lattice, charge, spin, and electronic behaviors underlying the Eu-Mn charge transfer in a strongly correlated system of EuMnO3 were investigated. The potential valence transition from Eu3+/Mn3+ to Eu2+/Mn4+ was observed in a compressed lattice with little distortions, which is achieved under hydrostatic pressure and external strain. The intraplane antiferromagnetism (AFM) of Mn is proved to be instrumental in the emergence of Eu2+. Furthermore, we calculated the magnetic exchange interactions within two equilibrium structures of Eu3+Mn3+O3 and Eu2+Mn4+O3. Mn-Mn ferromagnetic exchange in the ab-plane is enhanced strongly in the Eu2+Mn4+O3 structure, contributing to the existence of mixed states. The versatile electronic structures were obtained within the Eu2+Mn4+O3 phase by imposing different magnetic configurations on the Eu and Mn sublattice, attributed to the coupling of charge transfer and magnetic orderings. It is found that the intraplane ferromagnetic ordering of Mn leads to a metallic electronic structure with the coexistence of Eu2+ and Eu3+, while the intraplane AFM Mn spin ordering leads to insulating states only with Eu2+. Notably, a half-metallic characteristic emerges at the magnetic ground state of CF ordering (C-type AFM for the Eu sublattice and ferromagnetic for the Mn sublattice), which makes such a supposed phase more intriguing than the conventional experimental phase. Additionally, the mixture of delocalized 4f with 5d states of Eu in the background of Mn 3d and O 2p orbitals implies a pathway of Eu 4f 5d ↔ O 2p ↔ Mn 3d for charge transfer between Eu and Mn. Our calculation shows that the Eu-Mn charge transfer could be expected in compressed EuMnO3 and the introduction of Eu2+ 4f states near the Fermi level plays an important role in manipulating the interlinks of charge and spin together with electronic behaviors.

14.
Crit Rev Food Sci Nutr ; : 1-22, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33435726

RESUMO

The antioxidant ability is the link and bridge connecting a variety of biological activities. Citrus flavonoids play an essential role in regulating oxidative stress and are an important source of daily intake of antioxidant supplements. Many studies have shown that citrus flavonoids promote health through antioxidation. In this review, the biosynthesis, composition and distribution of citrus flavonoids were concluded. The detection methods of antioxidant capacity of citrus flavonoids were divided into four categories: chemical, cellular, animal and clinical antioxidant capacity evaluation systems. The modeling methods, applicable scenarios, and their relative merits were compared based on these four systems. The antioxidant functions of citrus flavonoids under different evaluation systems were also discussed, especially the regulation of the Nrf2-antioxidases pathway. Some shortcomings in the current research were pointed out, and some suggestions for progress were put forward.

15.
Biomed Pharmacother ; 137: 111274, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33517190

RESUMO

Oxidative stress and inflammation are important pathogenic factors of diabetic retinopathy (DR). DR remains the most common ocular complication caused by diabetes mellitus (DM) and is the leading cause of visual impairment in working-aged people worldwide. Melatonin has attracted extensive attention due to its potent antioxidant and anti-inflammatory effects. In the present study, melatonin inhibited oxidative stress and inflammation by enhancing the expression and activity of silent information regulator factor 2-related enzyme 1 (Sirt1) both in in vitro and in vivo models of DR, and the Sirt1 inhibitor EX-527 counteracted melatonin-mediated antioxidant and anti-inflammatory effects on Müller cells. Moreover, melatonin enhanced Sirt1 activity through the maternally expressed gene 3 (MEG3)/miR-204 axis, leading to the deacetylation of the Sirt1 target genes forkhead box o1 (Foxo1) and nuclear factor kappa B (NF-κB) subunit p65, eventually contribute to the alleviation of oxidative stress and inflammation. The study revealed that melatonin promotes the Sirt1 pathway, thereby protecting the retina from DM-induced damage.

16.
Biosens Bioelectron ; 173: 112832, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33234387

RESUMO

This work established an immobilization-free photoelectrochemical (PEC) biosensor for ultrasensitive determination of carcinoembryonic antigen (CEA) based on the DNA-functionalized metal-organic frameworks (MOFs) and T7 exonuclease-aided recycling amplification. In this proposal, MOFs were served as nanocarriers for efficient encapsulation of electron donors, while an ingeniously designed hairpin probe (HP) employed as the recognition element. The recognition of CEA by its aptamer sequence in HP triggered the conformational change and the T7 exonuclease-aided recycling amplification, which opened the pore of MOFs to release a large number of electron donors, producing a significantly increased photocurrent. Benefitting from the high loading ability of MOFs and the excellent amplification efficiency of the T7 exonuclease-assisted recycling process, the proposed biosensor is capable of ultrasensitive and highly selective determination of CEA with a detection limit down to 0.36 fg mL-1 and a wide linear range from 1.0 fg mL-1 to 10 ng mL-1. Moreover, the proposed biosensor can also apply to measure CEA in spiked serum samples, indicating that this PEC biosensor holds excellent potential for application in bioanalysis and early disease diagnosis.

17.
J Hazard Mater ; 401: 123355, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-32659580

RESUMO

A highly reactive hollow tubular g-C3N4 isotype heterojunction (SCN-CN) was designed to enhance visible light absorption and manipulate the directed transfer of electrons and holes. The results of UV-vis DRS, XPS valence band and DFT theoretical calculations indicated S doping increases the visible-light absorption capacity and changed the ba nd gap structure of g-C3N4 (CN), resulting in the transfer of electrons from the CN to the SCN and holes from the SCN to the CN under visible light. In addition, the tubular structure of the SCN-CN facilitated the transfer of electrons in the longitudinal direction, which reduced charge carrier recombination. Furthermore, the optical properties, electronic structure, and electron transfer of SCN-CN were also studied by experiments and theoretical calculations. The antibiotic tetracycline hydrochloride (TCH) and dye Rhodamine B (RHB) were subjected to evaluate the photocatalytic performance of SCN-CN. The scavenger tests and ESR data showed that the h+, ·O2- and ·OH worked together in the photocatalytic process. Moreover, the photocatalytic degradation pathway was analyzed by LC-MS. This study synthesized a hollow tubular CN isotype heterojunction with high visible-light photocatalytic performance and provided a theoretical basis for CN isotype heterojunction.

18.
Sci Rep ; 10(1): 21351, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33288842

RESUMO

Semimetals are a new kind of quantum materials, in which the conduction and valence bands cross each other near the Fermi level. Based on density-functional theory calculations and symmetry analysis, we propose nodal-line semimetals in layered stacked black phosphorus (BP) films which are designed to have a mirror symmetry lying in the BP layer plane and thus rendering them different from the BP film systems previously studied. A closed nodal-line degenerate band can appear around the Fermi level in the BP films after a biaxial compressive strain is applied. The calculated Z2 number of Z2 = - 1 indicates the robustness of the nodal-line semimetals obtained in the BP films, protected by the in-plane mirror symmetry. Intriguingly, with the increase of the film thickness, a smaller biaxial compressive strain is required to produce the nodal-line semimetals, more accessible in experiments. Our results provide a promising route to carrying out the nodal-line semimetals based on various two-dimensional materials.

19.
Cell Death Dis ; 11(11): 1016, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33247124

RESUMO

Wet age-related macular degeneration, which is characterized by choroidal neovascularization (CNV) and induces obvious vision loss. Vascular endothelial growth factor (VEGF) family member VEGF-A (also named as VEGF) and its receptor VEGFR2 contribute to the pathogenesis of CNV. Choroidal endothelial cells (CECs) secret C-C motif chemokine ligand 2 (CCL2), which attracts macrophages to CNV lesion and promotes macrophage M1 polarization. Accordingly, infiltrating macrophages secret inflammatory cytokines to promote CNV. In vivo, intravitreal injection of fruquintinib (HMPL-013), an antitumor neovascularization drug, alleviated mouse CNV formation without obvious ocular toxicity. Meanwhile, HMPL-013 inhibited VEGF/VEGFR2 binding in CECs and macrophages, as well as macrophage M1 polarization. In vitro, noncontact coculture of human choroidal vascular endothelial cells (HCVECs) and macrophages under hypoxia conditions was established. HMPL-013 downregulated VEGF/VEGFR2/phosphoinositide-3-kinase/protein kinase B (AKT)/nuclear factor kappa B pathway and CCL2 secretion in HCVECs, as well as VEGF/VEGFR2-induced macrophage M1 polarization under hypoxia condition. In addition, HMPL-013 inhibited HCEVC derived CCL2-induced macrophage migration and M1 polarization, along with macrophage M1 polarization-induced HCVECs proliferation, migration, and tube formation. Altogether, HMPL-013 alleviated CNV formation might via breaking detrimental cross talk between CECs and macrophages.

20.
Emerg Microbes Infect ; : 1-27, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33179566

RESUMO

Rapid accumulation of viral proteins in host cells render viruses highly dependent on cellular chaperones including heat shock protein 90 (Hsp90). Three highly pathogenic human coronaviruses, including MERS-CoV, SARS-CoV and SARS-CoV-2, have emerged in the past 2 decades. However, there is no approved antiviral agent against these coronaviruses. We inspected the role of Hsp90 for coronavirus propagation. First, an Hsp90 inhibitor, 17-AAG, significantly suppressed MERS-CoV propagation in cell lines and physiological-relevant human intestinal organoids. Second, siRNA depletion of Hsp90ß, but not Hsp90α, significantly restricted MERS-CoV replication and abolished virus spread. Third, Hsp90ß interaction with MERS-CoV nucleoprotein (NP) was revealed in a co-immunoprecipitation assay. Hsp90ß is required to maintain NP stability. Fourth, 17-AAG substantially inhibited the propagation of SARS-CoV and SARS-CoV-2. Collectively, Hsp90 is a host dependency factor for human coronavirus MERS-CoV, SARS-CoV and SARS-COV-2. Hsp90 inhibitors can be repurposed as a potent and broad-spectrum antiviral against human coronaviruses.

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