scholarly journals Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein

2014 ◽  
Vol 194 ◽  
pp. 200-210 ◽  
Author(s):  
Shuai Xia ◽  
Qi Liu ◽  
Qian Wang ◽  
Zhiwu Sun ◽  
Shan Su ◽  
...  
Keyword(s):  
Middle East ◽  
Middle East Respiratory Syndrome ◽  
Spike Protein ◽  
Entry Inhibitors

scholarly journals Peptide-Protein Interaction Studies of Antimicrobial Peptides Targeting Middle East Respiratory Syndrome Coronavirus Spike Protein: An In Silico Approach

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Sabeena Mustafa ◽  
Hanan Balkhy ◽  
Musa Gabere
Keyword(s):  
Middle East ◽  
Antimicrobial Peptides ◽  
Protein Interactions ◽  
In Silico ◽  
Therapeutic Option ◽  
Binding Mode ◽  
Middle East Respiratory Syndrome ◽  
Spike Protein ◽  
In Silico Docking ◽  
Peptide Database

There is no effective therapeutic or vaccine for Middle East Respiratory Syndrome and this study attempts to find therapy using peptide by establishing a basis for the peptide-protein interactions through in silico docking studies for the spike protein of MERS-CoV. The antimicrobial peptides (AMPs) were retrieved from the antimicrobial peptide database (APD3) and shortlisted based on certain important physicochemical properties. The binding mode of the shortlisted peptides was measured based on the number of clusters which forms in a protein-peptide docking using Piper. As a result, we identified a list of putative AMPs which binds to the spike protein of MERS-CoV, which may be crucial in providing the inhibitory action. It is observed that seven putative peptides have good binding score based on cluster size cutoff of 208. We conclude that seven peptides, namely, AP00225, AP00180, AP00549, AP00744, AP00729, AP00764, and AP00223, could possibly have binding with the active site of the MERS-CoV spike protein. These seven AMPs could serve as a therapeutic option for MERS and enhance its treatment outcome.

scholarly journals Blocking transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) in llamas by vaccination with a recombinant spike protein

2019 ◽  
Vol 8 (1) ◽  
pp. 1593-1603 ◽  
Author(s):  
Jordi Rodon ◽  
Nisreen M. A. Okba ◽  
Nigeer Te ◽  
Brenda van Dieren ◽  
Berend-Jan Bosch ◽  
...  
Keyword(s):  
Middle East ◽  
Middle East Respiratory Syndrome ◽  
Spike Protein

scholarly journals Conjugation of Human β-Defensin 2 to Spike Protein Receptor-Binding Domain Induces Antigen-Specific Protective Immunity against Middle East Respiratory Syndrome Coronavirus Infection in Human Dipeptidyl Peptidase 4 Transgenic Mice

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 635
Author(s):  
Ju Kim ◽  
Ye Lin Yang ◽  
Yongsu Jeong ◽  
Yong-Suk Jang
Keyword(s):  
Middle East ◽  
Immune Responses ◽  
Receptor Binding ◽  
Dipeptidyl Peptidase ◽  
Binding Domain ◽  
Middle East Respiratory Syndrome ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Dipeptidyl Peptidase 4 ◽  
Protein Receptor

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory symptoms. Due to the lack of medical countermeasures, effective and safe vaccines against MERS-CoV infection are urgently required. Although different types of candidate vaccines have been developed, their immunogenicity is limited, and the dose and administration route need optimization to achieve optimal protection. We here investigated the potential use of human β-defensin 2 (HBD 2) as an adjuvant to enhance the protection provided by MERS-CoV vaccination. We found that immunization of human dipeptidyl peptidase 4 (hDPP4)-transgenic (hDPP4-Tg) mice with spike protein receptor-binding domain (S RBD) conjugated with HBD 2 (S RBD-HBD 2) induced potent antigen (Ag)-specific adaptive immune responses and protected against MERS-CoV infection. In addition, immunization with S RBD-HBD 2 alleviated progressive pulmonary fibrosis in the lungs of MERS-CoV-infected hDPP4-Tg mice and suppressed endoplasmic reticulum stress signaling activation upon viral infection. Compared to intramuscular administration, intranasal administration of S RBD-HBD 2 induced more potent mucosal IgA responses and was more effective for protecting against intranasal MERS-CoV infection. In conclusion, our findings suggest that HBD 2 potentiates Ag-specific immune responses against viral Ag and can be used as an adjuvant enhancing the immunogenicity of subunit vaccine candidates against MERS-CoV.

scholarly journals Effect of Fc Fusion on Folding and Immunogenicity of Middle East Respiratory Syndrome Coronavirus Spike Protein

2019 ◽  
Vol 29 (5) ◽  
pp. 813-819 ◽  
Author(s):  
Jungmin Chun ◽  
Yeondong Cho ◽  
Ki Hoon Park ◽  
Hanul Choi ◽  
Hansam Cho ◽  
...  
Keyword(s):  
Middle East ◽  
Middle East Respiratory Syndrome ◽  
Spike Protein

scholarly journals Binding and entering: COVID finds a new home

2021 ◽  
Vol 17 (8) ◽  
pp. e1009857
Author(s):  
Michelle N. Vu ◽  
Vineet D. Menachery
Keyword(s):  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Common Cold ◽  
Binding Domain ◽  
Middle East Respiratory Syndrome ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Protease Cleavage ◽  
Pandemic Virus

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerged as a virus with a pathogenicity closer to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and a transmissibility similar to common cold coronaviruses (CoVs). In this review, we briefly discuss the features of the receptor-binding domain (RBD) and protease cleavage of the SARS-CoV-2 spike protein that enable SARS-CoV-2 to be a pandemic virus.

scholarly journals Mutations in the Spike Protein of Middle East Respiratory Syndrome Coronavirus Transmitted in Korea Increase Resistance to Antibody-Mediated Neutralization

2018 ◽  
Vol 93 (2) ◽  
Author(s):  
Hannah Kleine-Weber ◽  
Mahmoud Tarek Elzayat ◽  
Lingshu Wang ◽  
Barney S. Graham ◽  
Marcel A. Müller ◽  
...  
Keyword(s):  
Middle East ◽  
Protein Binding ◽  
Receptor Binding ◽  
Viral Entry ◽  
Middle East Respiratory Syndrome ◽  
Spike Protein ◽  
Target Cells ◽  
S Protein ◽  
Hospital Outbreak ◽  
The Republic

ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) poses a threat to public health. The virus is endemic in the Middle East but can be transmitted to other countries by travel activity. The introduction of MERS-CoV into the Republic of Korea by an infected traveler resulted in a hospital outbreak of MERS that entailed 186 cases and 38 deaths. The MERS-CoV spike (S) protein binds to the cellular protein DPP4 via its receptor binding domain (RBD) and mediates viral entry into target cells. During the MERS outbreak in Korea, emergence and spread of viral variants that harbored mutations in the RBD, D510G and I529T, was observed. Counterintuitively, these mutations were found to reduce DPP4 binding and viral entry into target cells. In this study, we investigated whether they also exerted proviral effects. We confirm that changes D510G and I529T reduce S protein binding to DPP4 but show that this reduction only translates into diminished viral entry when expression of DPP4 on target cells is low. Neither mutation modulated S protein binding to sialic acids, S protein activation by host cell proteases, or inhibition of S protein-driven entry by interferon-induced transmembrane proteins. In contrast, changes D510G and I529T increased resistance of S protein-driven entry to neutralization by monoclonal antibodies and sera from MERS patients. These findings indicate that MERS-CoV variants with reduced neutralization sensitivity were transmitted during the Korean outbreak and that the responsible mutations were compatible with robust infection of cells expressing high levels of DPP4. IMPORTANCE MERS-CoV has pandemic potential, and it is important to identify mutations in viral proteins that might augment viral spread. In the course of a large hospital outbreak of MERS in the Republic of Korea in 2015, the spread of a viral variant that contained mutations in the viral spike protein was observed. These mutations were found to reduce receptor binding and viral infectivity. However, it remained unclear whether they also exerted proviral effects. We demonstrate that these mutations reduce sensitivity to antibody-mediated neutralization and are compatible with robust infection of target cells expressing large amounts of the viral receptor DPP4.

scholarly journals Genomic Sequencing and Analysis of Eight Camel-Derived Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Isolates in Saudi Arabia

Viruses ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 611
Author(s):  
Badr M. Al-Shomrani ◽  
Manee M. Manee ◽  
Sultan N. Alharbi ◽  
Mussad A. Altammami ◽  
Manal A. Alshehri ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Middle East ◽  
Neutralizing Antibodies ◽  
3D Structure ◽  
Arabian Gulf ◽  
Cell Epitope ◽  
Middle East Respiratory Syndrome ◽  
Spike Protein ◽  
Dromedary Camel ◽  
Gulf Countries

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans; the second-largest and most deadly outbreak to date occurred in Saudi Arabia. The dromedary camel is considered a possible host of the virus and also to act as a reservoir, transmitting the virus to humans. Here, we studied evolutionary relationships for 31 complete genomes of betacoronaviruses, including eight newly sequenced MERS-CoV genomes isolated from dromedary camels in Saudi Arabia. Through bioinformatics tools, we also used available sequences and 3D structure of MERS-CoV spike glycoprotein to predict MERS-CoV epitopes and assess antibody binding affinity. Phylogenetic analysis showed the eight new sequences have close relationships with existing strains detected in camels and humans in Arabian Gulf countries. The 2019-nCov strain appears to have higher homology to both bat coronavirus and SARS-CoV than to MERS-CoV strains. The spike protein tree exhibited clustering of MERS-CoV sequences similar to the complete genome tree, except for one sequence from Qatar (KF961222). B cell epitope analysis determined that the MERS-CoV spike protein has 24 total discontinuous regions from which just six epitopes were selected with score values of >80%. Our results suggest that the virus circulates by way of camels crossing the borders of Arabian Gulf countries. This study contributes to finding more effective vaccines in order to provide long-term protection against MERS-CoV and identifying neutralizing antibodies.

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