scholarly journals Mapping the Specific Amino Acid Residues That Make Hamster DPP4 Functional as a Receptor for Middle East Respiratory Syndrome Coronavirus

2016 ◽  
Vol 90 (11) ◽  
pp. 5499-5502 ◽  
Author(s):  
Neeltje van Doremalen ◽  
Kerri L. Miazgowicz ◽  
Vincent J. Munster
Keyword(s):  
Amino Acids ◽  
Middle East ◽  
Case Fatality ◽  
Small Animal ◽  
Middle East Respiratory Syndrome ◽  
The Novel ◽  
Amino Acid Residues ◽  
Specific Amino Acid ◽  
Dipeptidyl Peptidase 4 ◽  
Protein Functions

ABSTRACTThe novel emerging coronavirus Middle East respiratory syndrome coronavirus (MERS-CoV) binds to its receptor, dipeptidyl peptidase 4 (DPP4), via 14 interacting amino acids. We previously showed that if the five interacting amino acids which differ between hamster and human DPP4 are changed to the residues found in human DPP4, hamster DPP4 does act as a receptor. Here, we show that the functionality of hamster DPP4 as a receptor is severely decreased if less than 4 out of 5 amino acids are changed.IMPORTANCEThe novel emerging coronavirus MERS-CoV has infected >1,600 people worldwide, and the case fatality rate is ∼36%. In this study, we show that by changing 4 amino acids in hamster DPP4, this protein functions as a receptor for MERS-CoV. This work is vital in the development of new small-animal models, which will broaden our understanding of MERS-CoV and be instrumental in the development of countermeasures.

scholarly journals Genetic Insights into the Middle East Respiratory Syndrome Coronavirus Infection among Saudi People

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1193
Author(s):  
Hatem A. Abuelizz ◽  
Maha M. AlRasheed ◽  
Ali Alhoshani ◽  
Tariq Alhawassi
Keyword(s):  
Amino Acid ◽  
Middle East ◽  
Point Mutations ◽  
Middle East Respiratory Syndrome ◽  
Atypical Pneumonia ◽  
Amino Acid Residues ◽  
Genome Database ◽  
Dipeptidyl Peptidase 4 ◽  
Dpp4 Inhibitors ◽  
Medical City

Background: The Middle East respiratory syndrome coronavirus (MERS-CoV) was isolated for the first time in Saudi Arabia from a patient suffering from atypical pneumonia. The Saudi Genome database was built by King Abdulaziz Medical City via the next-generation sequencing of 7000 candidates. Method: A large list of point mutations were reported in the region of the dipeptidyl peptidase 4 (DPP4) gene. The DPP4 amino acid residues correlated to MERS-CoV entry and the site of activity of DPP4 inhibitors was investigated. We retrieved the SNPs (Single-Nucleotide Polymorphism) with a variation frequency of >0.05. Results: SNP 2:162,890,175 and SNP 2:162,891,848 in the intronic region were located within 50 bp of amino acid residues responsible for MERS-CoV entry, amino acids 259–296 and 205–258, respectively. The variation frequency of SNP 2:162,890,175 was 2321 out of 2379 screened individuals. Moreover, mutation of SNP 2:162,891,848, which is located near amino acid residues E205 and E206 (crucial for the activity of DPP4 inhibitors), occurred in 76 out of 2379 screened individuals. Conclusions: Our study shows high variation frequency in the DPP4 region reported in the Saudi Genome database. The identified SNPs are of high significance for MERS-CoV infection in better understanding disease pathogenesis.

scholarly journals Wild-type and innate immune-deficient mice are not susceptible to the Middle East respiratory syndrome coronavirus

2014 ◽  
Vol 95 (2) ◽  
pp. 408-412 ◽  
Author(s):  
Christopher M. Coleman ◽  
Krystal L. Matthews ◽  
Lindsay Goicochea ◽  
Matthew B. Frieman
Keyword(s):  
Middle East ◽  
Mouse Model ◽  
Small Animal ◽  
Innate Immune ◽  
Middle East Respiratory Syndrome ◽  
Highly Pathogenic ◽  
Dipeptidyl Peptidase 4 ◽  
Low Level ◽  
Pathogenic Virus ◽  
Deficient Mice

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging highly pathogenic virus causing almost 50 % lethality in infected individuals. The development of a small-animal model is critical for the understanding of this virus and to aid in development of countermeasures against MERS-CoV. We found that BALB/c, 129/SvEv and 129/SvEv STAT1 knockout mice are not permissive to MERS-CoV infection. The lack of infection may be due to the low level of mRNA and protein for the MERS-CoV receptor, dipeptidyl peptidase 4 (DPP4), in the lungs of mice. The low level of DPP4 in the lungs likely contributes to the lack of viral replication in these mouse models and suggests that a transgenic mouse model expressing DPP4 to higher levels is necessary to create a mouse model for MERS-CoV.

scholarly journals Human Monoclonal Antibody Cocktail for the Treatment or Prophylaxis of Middle East Respiratory Syndrome Coronavirus

2021 ◽  
Author(s):  
Sumathi Sivapalasingam ◽  
George A Saviolakis ◽  
Kirsten Kulcsar ◽  
Aya Nakamura ◽  
Thomas Conrad ◽  
...  
Keyword(s):  
Middle East ◽  
Adverse Events ◽  
Phase 1 ◽  
Human Monoclonal Antibody ◽  
Preclinical Study ◽  
Middle East Respiratory Syndrome ◽  
Lung Pathology ◽  
Phase 1 Study ◽  
Serious Adverse Events ◽  
Dipeptidyl Peptidase 4

Abstract Background REGN3048 and REGN3051 are human monoclonal antibodies (mAb) targeting the spike glycoprotein on the Middle East respiratory syndrome coronavirus (MERS-CoV), which binds to the receptor dipeptidyl peptidase-4 (DPP4) and is necessary for infection of susceptible cells. Methods Preclinical study: REGN3048, REGN3051 and isotype immunoglobulin G (IgG) were administered to humanized DPP4 (huDPP4) mice 1 day prior to and 1 day after infection with MERS-CoV (Jordan strain). Virus titers and lung pathology were assessed. Phase 1 study: healthy adults received the combined mAb (n = 36) or placebo (n = 12) and followed for 121 days. Six dose levels were studied. Strict safety criteria were met prior to dose escalation. Results Preclinical study: REGN3048 plus REGN3051, prophylactically or therapeutically, was substantially more effective for reducing viral titer, lung inflammation, and pathology in huDPP4 mice compared with control antibodies and to each antibody monotherapy. Phase 1 study: REGN3048 plus REGN3051 was well tolerated with no dose-limiting adverse events, deaths, serious adverse events, or infusion reactions. Each mAb displayed pharmacokinetics expected of human IgG1 antibodies; it was not immunogenic. Conclusions REGN3048 and REGN3051 in combination were well tolerated. The clinical and preclinical data support further development for the treatment or prophylaxis of MERS-CoV infection.

scholarly journals Limited Genetic Diversity Detected in Middle East Respiratory Syndrome-Related Coronavirus Variants Circulating in Dromedary Camels in Jordan

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 592
Author(s):  
Stephanie N. Seifert ◽  
Jonathan E. Schulz ◽  
Stacy Ricklefs ◽  
Michael Letko ◽  
Elangeni Yabba ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Middle East ◽  
United Arab Emirates ◽  
Sequence Data ◽  
Case Fatality ◽  
High Sensitivity ◽  
Middle East Respiratory Syndrome ◽  
Full Genome Sequence ◽  
Genome Sequences ◽  
Dromedary Camels

Middle East respiratory syndrome-related coronavirus (MERS-CoV) is a persistent zoonotic pathogen with frequent spillover from dromedary camels to humans in the Arabian Peninsula, resulting in limited outbreaks of MERS with a high case-fatality rate. Full genome sequence data from camel-derived MERS-CoV variants show diverse lineages circulating in domestic camels with frequent recombination. More than 90% of the available full MERS-CoV genome sequences derived from camels are from just two countries, the Kingdom of Saudi Arabia (KSA) and United Arab Emirates (UAE). In this study, we employ a novel method to amplify and sequence the partial MERS-CoV genome with high sensitivity from nasal swabs of infected camels. We recovered more than 99% of the MERS-CoV genome from field-collected samples with greater than 500 TCID50 equivalent per nasal swab from camel herds sampled in Jordan in May 2016. Our subsequent analyses of 14 camel-derived MERS-CoV genomes show a striking lack of genetic diversity circulating in Jordan camels relative to MERS-CoV genome sequences derived from large camel markets in KSA and UAE. The low genetic diversity detected in Jordan camels during our study is consistent with a lack of endemic circulation in these camel herds and reflective of data from MERS outbreaks in humans dominated by nosocomial transmission following a single introduction as reported during the 2015 MERS outbreak in South Korea. Our data suggest transmission of MERS-CoV among two camel herds in Jordan in 2016 following a single introduction event.

scholarly journals Origins and pathogenesis of Middle East respiratory syndrome-associated coronavirus: recent advances

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1628 ◽  
Author(s):  
Stephen A. Goldstein ◽  
Susan R. Weiss
Keyword(s):  
Immune Response ◽  
Middle East ◽  
Animal Models ◽  
Case Fatality ◽  
Innate Immune ◽  
Middle East Respiratory Syndrome ◽  
Live Virus ◽  
Novel Proteins ◽  
Significant Research ◽  
African Bats

Middle East respiratory syndrome-associated coronavirus (MERS-CoV) has been a significant research focus since its discovery in 2012. Since 2012, 2,040 cases and 712 deaths have been recorded (as of August 11, 2017), representing a strikingly high case fatality rate of 36%. Over the last several years, MERS-CoV research has progressed in several parallel and complementary directions. This review will focus on three particular areas: the origins and evolution of MERS-CoV, the challenges and achievements in the development of MERS-CoV animal models, and our understanding of how novel proteins unique to MERS-CoV counter the host immune response. The origins of MERS-CoV, likely in African bats, are increasingly clear, although important questions remain about the establishment of dromedary camels as a reservoir seeding human outbreaks. Likewise, there have been important advances in the development of animal models, and both non-human primate and mouse models that seem to recapitulate human disease are now available. How MERS-CoV evades and inhibits the host innate immune response remains less clear. Although several studies have identified MERS-CoV proteins as innate immune antagonists, little of this work has been conducted using live virus under conditions of actual infection, but rather with ectopically expressed proteins. Accordingly, considerable space remains for major contributions to understanding unique ways in which MERS-CoV interacts with and modulates the host response. Collectively, these areas have seen significant advances over the last several years but continue to offer exciting opportunities for discovery.

scholarly journals Does the novel coronavirus 2019 like heart more than the other family members of coronaviruses?

2020 ◽  
Vol 12 (2) ◽  
pp. 156-157
Author(s):  
Mohammad Mostafa Ansari Ramandi ◽  
Mohammadreza Baay ◽  
Nasim Naderi
Keyword(s):  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Family Members ◽  
Middle East Respiratory Syndrome ◽  
The Other ◽  
The Novel ◽  
The World ◽  
Future Challenges ◽  
Novel Coronavirus ◽  
Coronavirus Infections

The disaster due to the novel coronavirus disease 2019 (COVID-19) around the world has made investigators enthusiastic about working on different aspects of COVID-19. However, although the pandemic of COVID-19 has not yet ended, it seems that COVID-19 compared to the other coronavirus infections (the Middle East Respiratory Syndrome [MERS] and Severe Acute Respiratory Syndrome [SARS]) is more likely to target the heart. Comparing the previous presentations of the coronavirus family and the recent cardiovascular manifestations of COVID-19 can also help in predicting possible future challenges and taking measures to tackle these issues.

scholarly journals Middle East Respiratory Syndrome (MERS) Infection in Hematological and Oncological Patients: A Case Series from a Tertiary Care Center in Saudi Arabia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5871-5871 ◽  
Author(s):  
Ahmed Alaskar ◽  
Mohammed Bosaeed ◽  
Hina Rehan ◽  
May Anne Mendoza ◽  
Bader Alahmari ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Middle East ◽  
Clinical Presentation ◽  
Conflicts Of Interest ◽  
Tertiary Care ◽  
Case Series ◽  
Case Fatality ◽  
Middle East Respiratory Syndrome ◽  
Future Research ◽  
Fatality Rate

We present the largest to date of a case series of nine patients with hematological and oncological malignancies who were infected with Middle East Respiratory Syndrome Coronavirus (MERS-CoV). MERS-CoV is a novel beta-coronavirus with a high fatality rate in comorbid patients. The majority of MERS cases globally were reported from Saudi Arabia (1983 cases, including 745 related deaths with a case-fatality rate of 37.5%) according to the WHO update of February 2019. All were clinically stable before acquiring the virus. Most of the cases had an active disease as relapse or refractory with three cases being neutropenic. The clinical presentation and radiological features of the patients were variable and inconsistent (Table 1). Diagnosis was confirmed with RT-PCR assays targeting upstream of the E gene and the open-reading frame gene 1a which had to be done repeatedly and required an average of 3 (with max. of 7) samples for a test to be positive (Table 2). All the patients developed respiratory failure, were admitted to the critical care unit (ICU) and required mechanical ventilation. The length of hospital stay ranged from 15 - 48, with an average of 24 days. Unfortunately, all nine patients died within days after admission to the ICU. In addition, the time from diagnosis to death has an average of 9 days ranging from 2-24 days, respectively. In conclusion, MERS CoV infection in hematology/oncology patients has a very poor prognosis regardless of the status of the underlying disease. The clinical presentation is not distinctive and confirming the diagnosis requires numerous respiratory samples. Measures to prevent nosocomial outbreaks should include proper compliance with personal protection equipment by health-care workers when managing patients with suspected and confirmed MERS-CoV infection and prompt isolation of infected patients. Future research is required to enhance our understanding of the disease and to evaluate superior diagnostic and therapeutic options. Disclosures No relevant conflicts of interest to declare.

A Review of the Virology of SARS-CoV-2

2020 ◽  
Vol 7 (1) ◽  
pp. 69-77
Author(s):  
Aldonna Maria Susngi ◽  
◽  
Clara Ermine Sawian
Keyword(s):  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Causative Agent ◽  
Middle East Respiratory Syndrome ◽  
The Novel ◽  
Highly Pathogenic ◽  
Key Features

The novel severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19) is a β-coronavirus, which also includes the highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome Coronavirus (MERS-CoV). Emerging in December 2019 from Wuhan, China, it has spread worldwide resulting in a pandemic that has not ended till date. This review highlights some of the key features of the virology of SARS-CoV-2.

Recent Advances in Photoredox Catalysis Enabled Functionalization of α-Amino Acids and Peptides: Concepts, Strategies and Mechanisms

Synthesis ◽  
2019 ◽  
Vol 51 (14) ◽  
pp. 2759-2791 ◽  
Author(s):  
Jian-Quan Liu ◽  
Andrey Shatskiy ◽  
Bryan S. Matsuura ◽  
Markus D. Kärkäs
Keyword(s):  
Amino Acids ◽  
Visible Light ◽  
Hypervalent Iodine ◽  
Amino Acid Residues ◽  
Photoredox Catalysis ◽  
Metal Catalysis ◽  
Specific Amino Acid ◽  
Recent Advances ◽  
Redox Active ◽  
Decarboxylative Coupling

The selective modification of α-amino acids and peptides constitutes a pivotal arena for accessing new peptide-based materials and therapeutics. In recent years, visible light photoredox catalysis has appeared as a powerful platform for the activation of small molecules via single-electron transfer events, allowing previously inaccessible reaction pathways to be explored. This review outlines the recent advances, mechanistic underpinnings, and opportunities of applying photoredox catalysis to the expansion of the synthetic repertoire for the modification of specific amino acid residues.1 Introduction2 Visible-Light-Mediated Functionalization of α-Amino Acids2.1 Decarboxylative Functionalization Involving Redox-Active Esters2.2 Direct Decarboxylative Coupling Strategies2.3 Hypervalent Iodine Reagents2.4 Dual Photoredox and Transition-Metal Catalysis2.5 Amination and Deamination Strategies3 Photoinduced Peptide Diversification3.1 Gese-Type Bioconjugation Methods3.2 Peptide Macrocyclization through Photoredox Catalysis3.3 Biomolecule Conjugation through Arylation3.4 C–H Functionalization Manifolds4 Conclusions and Outlook

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