Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus.

Abstract:

:The Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated in 2012, and circulated worldwide with high mortality. The continual outbreaks of MERS-CoV highlight the importance of developing antiviral therapeutics. Here, we rationally designed a novel fusion inhibitor named MERS-five-helix bundle (MERS-5HB) derived from the six-helix bundle (MERS-6HB) which was formed by the process of membrane fusion. MERS-5HB consists of three copies of heptad repeat 1 (HR1) and two copies of heptad repeat 2 (HR2) while MERS-6HB includes three copies each of HR1 and HR2. As it lacks one HR2, MERS-5HB was expected to interact with viral HR2 to interrupt the fusion step. What we found was that MERS-5HB could bind to HR2P, a peptide derived from HR2, with a strong affinity value (KD) of up to 0.24 nM. Subsequent assays indicated that MERS-5HB could inhibit pseudotyped MERS-CoV entry effectively with 50% inhibitory concentration (IC50) of about 1 μM. In addition, MERS-5HB significantly inhibited spike (S) glycoprotein-mediated syncytial formation in a dose-dependent manner. Further biophysical characterization showed that MERS-5HB was a thermo-stable α-helical secondary structure. The inhibitory potency of MERS-5HB may provide an attractive basis for identification of a novel inhibitor against MERS-CoV, as a potential antiviral agent.

journal_name

Viruses

journal_title

Viruses

authors

Sun Y,Zhang H,Shi J,Zhang Z,Gong R

doi

10.3390/v9090255

subject

Has Abstract

pub_date

2017-09-14 00:00:00

issue

9

issn

1999-4915

pii

v9090255

journal_volume

9

pub_type

杂志文章
  • Implications of HIV-1 Nef for "Shock and Kill" Strategies to Eliminate Latent Viral Reservoirs.

    abstract::Finding a cure for HIV is challenging because the virus is able to integrate itself into the host cell genome and establish a silent state, called latency, allowing it to evade antiviral drugs and the immune system. Various "shock and kill" strategies are being explored in attempts to eliminate latent HIV reservoirs. ...

    journal_title:Viruses

    pub_type: 杂志文章,评审

    doi:10.3390/v10120677

    authors: Kuang XT,Brockman MA

    更新日期:2018-11-30 00:00:00

  • A Novel Duplex Real-Time Reverse-Transcription PCR Assay for the Detection of Influenza A and the Novel Influenza A(H1N1) Strain.

    abstract::Timely implementation of antiviral treatment and other public health based responses are dependent on accurate and rapid diagnosis of the novel pandemic influenza A(H1N1) strain. In this study we developed a duplex real-time PCR (RT-PCR) (dFLU-TM) assay for the simultaneous detection of a broad range of influenza A su...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v1031204

    authors: Rockett RJ,Bialasiewicz S,Whiley DM,Bletchly C,Faux CE,Lambert SB,Nimmo GR,Nissen MD,Sloots TP

    更新日期:2009-12-01 00:00:00

  • Interactions of Human Dermal Dendritic Cells and Langerhans Cells Treated with Hyalomma Tick Saliva with Crimean-Congo Hemorrhagic Fever Virus.

    abstract::Crimean-Congo hemorrhagic fever virus is one the most important and wide spread tick-borne viruses. Very little is known about the transmission from the tick and the early aspects of pathogenesis. Here, we generate human cutaneous antigen presenting cells-dermal dendritic cells and Langerhans cells-from umbilical cord...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v10070381

    authors: Rodriguez SE,McAuley AJ,Gargili A,Bente DA

    更新日期:2018-07-20 00:00:00

  • Lambda gpP-DnaB Helicase Sequestration and gpP-RpoB Associated Effects: On Screens for Auxotrophs, Selection for Rif(R), Toxicity, Mutagenicity, Plasmid Curing.

    abstract::The bacteriophage lambda replication initiation protein P exhibits a toxic effect on its Escherichia coli (E. coli) host, likely due to the formation of a dead-end P-DnaB complex, sequestering the replicative DnaB helicase from further activity. Intracellular expression of P triggers SOS-independent cellular filamenta...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v8060172

    authors: Hayes S,Wang W,Rajamanickam K,Chu A,Banerjee A,Hayes C

    更新日期:2016-06-22 00:00:00

  • The IKK Kinases: Operators of Antiviral Signaling.

    abstract::The ability of a cell to combat an intracellular pathogen requires a mechanism to recognize the threat and elicit a transcriptional response against it. In the context of virus infection, the cell must take measures to inhibit viral replication, meanwhile, convey warning signals to neighboring cells of the imminent th...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v2010055

    authors: Pham AM,Tenoever BR

    更新日期:2010-01-01 00:00:00

  • A Flagellar Glycan-Specific Protein Encoded by Campylobacter Phages Inhibits Host Cell Growth.

    abstract::We previously characterized a carbohydrate binding protein, Gp047, derived from lytic Campylobacter phage NCTC 12673, as a promising diagnostic tool for the identification of Campylobacter jejuni and Campylobacter coli. We also demonstrated that this protein binds specifically to acetamidino-modified pseudaminic acid ...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v7122964

    authors: Javed MA,Sacher JC,van Alphen LB,Patry RT,Szymanski CM

    更新日期:2015-12-16 00:00:00

  • Equilibrium and kinetics of Sin Nombre hantavirus binding at DAF/CD55 functionalized bead surfaces.

    abstract::Decay accelerating factor (DAF/CD55) is targeted by many pathogens for cell entry. It has been implicated as a co-receptor for hantaviruses. To examine the binding of hantaviruses to DAF, we describe the use of Protein G beads for binding human IgG Fc domain-functionalized DAF ((DAF)₂-Fc). When mixed with Protein G be...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v6031091

    authors: Buranda T,Swanson S,Bondu V,Schaefer L,Maclean J,Mo Z,Wycoff K,Belle A,Hjelle B

    更新日期:2014-03-10 00:00:00

  • Successful Infection of Domestic Pigs by Ingestion of the European Soft Tick O. Erraticus That Fed on African Swine Fever Virus Infected Pig.

    abstract::African swine fever is a highly lethal hemorrhagic fever of Suidae, threatening pig production globally. Suidae can be infected by different ways like ingestion of contaminated feed, direct contact with infected animals or fomites, and biting by infected soft tick bites. As already described, European soft ticks (Orni...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v12030300

    authors: Pereira De Oliveira R,Hutet E,Duhayon M,Guionnet JM,Paboeuf F,Vial L,Le Potier MF

    更新日期:2020-03-11 00:00:00

  • Equine Immunoglobulin and Equine Neutralizing F(ab')₂ Protect Mice from West Nile Virus Infection.

    abstract::West Nile virus (WNV) is prevalent in Africa, Europe, the Middle East, West Asia, and North America, and causes epidemic encephalitis. To date, no effective therapy for WNV infection has been developed; therefore, there is urgent need to find an efficient method to prevent WNV disease. In this study, we prepared and e...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v8120332

    authors: Cui J,Zhao Y,Wang H,Qiu B,Cao Z,Li Q,Zhang Y,Yan F,Jin H,Wang T,Sun W,Feng N,Gao Y,Sun J,Wang Y,Perlman S,Zhao J,Yang S,Xia X

    更新日期:2016-12-18 00:00:00

  • Cell surface markers in HTLV-1 pathogenesis.

    abstract::The phenotype of HTLV-1-transformed CD4(+) T lymphocytes largely depends on defined viral effector molecules such as the viral oncoprotein Tax. In this review, we exemplify the expression pattern of characteristic lineage markers, costimulatory receptors and ligands of the tumor necrosis factor superfamily, cytokine r...

    journal_title:Viruses

    pub_type: 杂志文章,评审

    doi:10.3390/v3081439

    authors: Kress AK,Grassmann R,Fleckenstein B

    更新日期:2011-08-01 00:00:00

  • The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations.

    abstract::Emergence of human immunodeficiency virus type 1 (HIV-1) drug resistance arises from mutation fixation in the viral genome during antiretroviral therapy. Primary mutations directly confer antiviral drug resistance, while secondary mutations arise that do not confer drug resistance. The A62V amino acid substitution in ...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v10070376

    authors: Maldonado JO,Mansky LM

    更新日期:2018-07-19 00:00:00

  • Duck Plague Virus Promotes DEF Cell Apoptosis by Activating Caspases, Increasing Intracellular ROS Levels and Inducing Cell Cycle S-Phase Arrest.

    abstract:BACKGROUND:Duck plague virus (DPV) can induce apoptosis in duck embryo fibroblasts (DEFs) and in infected ducks, but the molecular mechanism of DPV-induced apoptosis remains unknown. METHODS:We first used qRT-PCR and a Caspase-Glo assay to determine whether the caspase protein family plays an important role in DPV-ind...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v11020196

    authors: Zhao C,Wang M,Cheng A,Yang Q,Wu Y,Jia R,Zhu D,Chen S,Liu M,Zhao X,Zhang S,Liu Y,Yu Y,Zhang L,Tian B,Rehman MU,Pan L,Chen X

    更新日期:2019-02-24 00:00:00

  • A filtration based technique for simultaneous SEM and TEM sample preparation for the rapid detection of pathogens.

    abstract::Diagnostic electron microscopy for infectious diseases has the advantage that "everything" in the specimen can be observed, without a priori knowledge of the likely identity of the microorganisms present in the sample. The classical specimen preparation method used employs a droplet of sample, which allows particles t...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v6093458

    authors: Beniac DR,Siemens CG,Wright CJ,Booth TF

    更新日期:2014-09-19 00:00:00

  • A Cell-Based ELISA to Improve the Serological Analysis of Anti-SARS-CoV-2 IgG.

    abstract::Knowledge of the antibody-mediated immune response to SARS-CoV-2 is crucial to understand virus immunogenicity, establish seroprevalence, and determine whether subjects or recovered patients are at risk for infection/reinfection and would therefore benefit from vaccination. Here, we describe a novel and simple cell-EL...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v12111274

    authors: Zarletti G,Tiberi M,De Molfetta V,Bossù M,Toppi E,Bossù P,Scapigliati G

    更新日期:2020-11-08 00:00:00

  • "FastCheckFLI PPR-like"-A Molecular Tool for the Fast Genome Detection of PPRV and Differential Diagnostic Pathogens.

    abstract::To assist the global eradication of peste des petits ruminants virus (PPRV), a molecular test for the rapid and reliable detection of PPRV was developed which additionally enables the detection of pathogens relevant for differential diagnostics. For this purpose, the necessary time frame of a magnetic bead-based nucle...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v12111227

    authors: Halecker S,Mettenleiter TC,Beer M,Hoffmann B

    更新日期:2020-10-29 00:00:00

  • Autophagy Induced by Simian Retrovirus Infection Controls Viral Replication and Apoptosis of Jurkat T Lymphocytes.

    abstract::Autophagy and apoptosis are two important evolutionarily conserved host defense mechanisms against viral invasion and pathogenesis. However, the association between the two pathways during the viral infection of T lymphocytes remains to be elucidated. Simian type D retrovirus (SRV) is an etiological agent of fatal sim...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v12040381

    authors: Zhu J,Yang L,Zhang Q,Meng J,Lu ZL,Rong R

    更新日期:2020-03-31 00:00:00

  • Structural and Functional Characterization of the Secondary Mutation N126K Selected by Various HIV-1 Fusion Inhibitors.

    abstract::Peptides derived from the C-terminal heptad repeat (CHR) region of HIV-1 gp41 is potent viral membrane fusion inhibitors, such as the first clinically approved peptide drug T20 and a group of newly-designed peptides. The resistance profiles of various HIV-1 fusion inhibitors were previously characterized, and the seco...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v12030326

    authors: Yu D,Su Y,Ding X,Zhu Y,Qin B,Chong H,Cui S,He Y

    更新日期:2020-03-18 00:00:00

  • Phylodynamic Analysis Complements Partner Services by Identifying Acute and Unreported HIV Transmission.

    abstract::Tailoring public health responses to growing HIV transmission clusters depends on accurately mapping the risk network through which it spreads and identifying acute infections that represent the leading edge of cluster growth. HIV transmission links, especially those involving persons with acute HIV infection (AHI), c...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v12020145

    authors: Campbell EM,Patala A,Shankar A,Li JF,Johnson JA,Westheimer E,Gay CL,Cohen SE,Switzer WM,Peters PJ

    更新日期:2020-01-27 00:00:00

  • Adenovirus E1A/E1B Transformed Amniotic Fluid Cells Support Human Cytomegalovirus Replication.

    abstract::The human cytomegalovirus (HCMV) replicates to high titers in primary human fibroblast cell cultures. A variety of primary human cells and some tumor-derived cell lines do also support permissive HCMV replication, yet at low levels. Cell lines established by transfection of the transforming functions of adenoviruses h...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v8020037

    authors: Krömmelbein N,Wiebusch L,Schiedner G,Büscher N,Sauer C,Florin L,Sehn E,Wolfrum U,Plachter B

    更新日期:2016-02-02 00:00:00

  • Evasion of the interferon-mediated antiviral response by filoviruses.

    abstract::The members of the filoviruses are recognized as some of the most lethal viruses affecting human and non-human primates. The only two genera of the Filoviridae family, Marburg virus (MARV) and Ebola virus (EBOV), comprise the main etiologic agents of severe hemorrhagic fever outbreaks in central Africa, with case fata...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v2010262

    authors: Cárdenas WB

    更新日期:2010-01-01 00:00:00

  • Isolation of a T7-Like Lytic Pasteurella Bacteriophage vB_PmuP_PHB01 and Its Potential Use in Therapy against Pasteurella multocida Infections.

    abstract::A lytic bacteriophage PHB01 specific for Pasteurella multocida type D was isolated from the sewage water collected from a pig farm. This phage had the typical morphology of the family Podoviridae, order Caudovirales, presenting an isometric polyhedral head and a short noncontractile tail. PHB01 was able to infect most...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v11010086

    authors: Chen Y,Guo G,Sun E,Song J,Yang L,Zhu L,Liang W,Hua L,Peng Z,Tang X,Chen H,Wu B

    更新日期:2019-01-21 00:00:00

  • Approaches for identification of HIV-1 entry inhibitors targeting gp41 pocket.

    abstract::The hydrophobic pocket in the HIV-1 gp41 N-terminal heptad repeat (NHR) domain plays an important role in viral fusion and entry into the host cell, and serves as an attractive target for development of HIV-1 fusion/entry inhibitors. The peptide anti-HIV drug targeting gp41 NHR, T-20 (generic name: enfuvirtide; brand ...

    journal_title:Viruses

    pub_type: 杂志文章,评审

    doi:10.3390/v5010127

    authors: Yu F,Lu L,Du L,Zhu X,Debnath AK,Jiang S

    更新日期:2013-01-11 00:00:00

  • Live Attenuated African Swine Fever Viruses as Ideal Tools to Dissect the Mechanisms Involved in Cross-Protection.

    abstract::African swine fever (ASF) has become the major threat for the global swine industry. Furthermore, the epidemiological situation of African swine fever virus (ASFV) in some endemic regions of Sub-Saharan Africa is worse than ever, with multiple virus strains and genotypes currently circulating in a given area. Despite ...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v12121474

    authors: Lopez E,van Heerden J,Bosch-Camós L,Accensi F,Navas MJ,López-Monteagudo P,Argilaguet J,Gallardo C,Pina-Pedrero S,Salas ML,Salt J,Rodriguez F

    更新日期:2020-12-21 00:00:00

  • Contemporary Zika Virus Isolates Induce More dsRNA and Produce More Negative-Strand Intermediate in Human Astrocytoma Cells.

    abstract::The recent emergence and rapid geographic expansion of Zika virus (ZIKV) poses a significant challenge for public health. Although historically causing only mild febrile illness, recent ZIKV outbreaks have been associated with more severe neurological complications, such as Guillain-Barré syndrome and fetal microcepha...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v10120728

    authors: Barnard TR,Rajah MM,Sagan SM

    更新日期:2018-12-19 00:00:00

  • Foamy virus budding and release.

    abstract::Like all other viruses, a successful egress of functional particles from infected cells is a prerequisite for foamy virus (FV) spread within the host. The budding process of FVs involves steps, which are shared by other retroviruses, such as interaction of the capsid protein with components of cellular vacuolar protei...

    journal_title:Viruses

    pub_type: 杂志文章,评审

    doi:10.3390/v5041075

    authors: Hütter S,Zurnic I,Lindemann D

    更新日期:2013-04-10 00:00:00

  • Marine Viruses: Key Players in Marine Ecosystems.

    abstract::Viruses were recognized as the causative agents of fish diseases, such as infectious pancreatic necrosis and Oregon sockeye disease, in the early 1960s [1], and have since been shown to be responsible for diseases in all marine life from bacteria to protists, mollusks, crustaceans, fish and mammals [2].[...]. ...

    journal_title:Viruses

    pub_type: 社论

    doi:10.3390/v9100302

    authors: Middelboe M,Brussaard CPD

    更新日期:2017-10-18 00:00:00

  • Temperature Sensitive Mutations in Influenza A Viral Ribonucleoprotein Complex Responsible for the Attenuation of the Live Attenuated Influenza Vaccine.

    abstract::Live attenuated influenza vaccines (LAIV) have prevented morbidity and mortality associated with influenza viral infections for many years and represent the best therapeutic option to protect against influenza viral infections in humans. However, the development of LAIV has traditionally relied on empirical methods, s...

    journal_title:Viruses

    pub_type: 杂志文章,评审

    doi:10.3390/v10100560

    authors: Martínez-Sobrido L,Peersen O,Nogales A

    更新日期:2018-10-15 00:00:00

  • Use of the Syrian hamster as a new model of ebola virus disease and other viral hemorrhagic fevers.

    abstract::Historically, mice and guinea pigs have been the rodent models of choice for therapeutic and prophylactic countermeasure testing against Ebola virus disease (EVD). Recently, hamsters have emerged as a novel animal model for the in vivo study of EVD. In this review, we discuss the history of the hamster as a research l...

    journal_title:Viruses

    pub_type: 杂志文章,评审

    doi:10.3390/v4123754

    authors: Wahl-Jensen V,Bollinger L,Safronetz D,de Kok-Mercado F,Scott DP,Ebihara H

    更新日期:2012-12-14 00:00:00

  • Preparation, Characterization and Diagnostic Valuation of Two Novel Anti-HPV16 E7 Oncoprotein Monoclonal Antibodies.

    abstract::At present, the clinical detection method of human papillomavirus (HPV) is mainly based on the PCR method. However, this method can only be used to detect HPV DNA and HPV types, and cannot be used to accurately predict cervical cancer. HPV16 E7 is an oncoprotein selectively expressed in cervical cancers. In this study...

    journal_title:Viruses

    pub_type: 杂志文章

    doi:10.3390/v12030333

    authors: Hu R,Dong Z,Zhang K,Pan G,Li C,Cui H

    更新日期:2020-03-19 00:00:00

  • An Insight into Cotton Leaf Curl Multan Betasatellite, the Most Important Component of Cotton Leaf Curl Disease Complex.

    abstract::Cotton leaf curl disease (CLCuD) is one of the most economically important diseases and is a constraint to cotton production in major producers, Pakistan and India. CLCuD is caused by monopartite plant viruses belonging to the family Geminiviridae (genus Begomovirus), in association with an essential, disease-specific...

    journal_title:Viruses

    pub_type: 杂志文章,评审

    doi:10.3390/v9100280

    authors: Zubair M,Zaidi SS,Shakir S,Amin I,Mansoor S

    更新日期:2017-09-29 00:00:00