scholarly journals Analysis of Codon Usage and Nucleotide Bias in Middle East Respiratory Syndrome Coronavirus Genes

2020 ◽  
Vol 16 ◽  
pp. 117693432091886 ◽  
Author(s):  
Snawar Hussain ◽  
Pottathil Shinu ◽  
Mohammed Monirul Islam ◽  
Muhammad Shahzad Chohan ◽  
Sahibzada Tasleem Rasool
Keyword(s):  
Middle East ◽  
Codon Usage ◽  
Vaccine Strain ◽  
Codon Usage Bias ◽  
Chemical Properties ◽  
Case Fatality ◽  
Middle East Respiratory Syndrome ◽  
Virulent Phenotype ◽  
Conserved Gene ◽  
A Minor

The Middle East Respiratory Syndrome (MERS) is an emerging disease caused by a recently identified human coronavirus (CoV). Over 2494 laboratory-confirmed cases and 858 MERS-related deaths have been reported from 27 countries. MERS-CoV has been associated with a high case fatality rate, especially in patients with pre-existing conditions. Despite the fatal nature of MERS-CoV infection, a comprehensive study to explore its evolution and adaptation in different hosts is lacking. We performed codon usage analyses on 4751 MERS-CoV genes and determined underlying forces that affect the codon usage bias in the MERS-CoV genome. The current analyses revealed a low but highly conserved, gene-specific codon usage bias in the MERS-CoV genome. The codon usage bias is mainly shaped by natural selection, while mutational pressure emerged as a minor factor affecting codon usage in some genes. Other contributory factors included CpG dinucleotide bias, physical and chemical properties of encoded proteins and gene length. Results reported in this study provide considerable insights into the molecular evaluation of MERS-CoV and could serve as a theoretical basis for optimizing MERS-CoV gene expression to study the functional relevance of various MERS-CoV proteins. Alternatively, an attenuated vaccine strain containing hundreds of silent mutations could be engineered. Codon de-optimization will not affect the amino acid sequence or antigenicity of a vaccine strain, but the sheer number of mutations would make viral reversion to a virulent phenotype extremely unlikely.

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 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.

scholarly journals Passive Immunotherapy with Dromedary Immune Serum in an Experimental Animal Model for Middle East Respiratory Syndrome Coronavirus Infection

2015 ◽  
Vol 89 (11) ◽  
pp. 6117-6120 ◽  
Author(s):  
Jincun Zhao ◽  
Ranawaka A. P. M. Perera ◽  
Ghazi Kayali ◽  
David Meyerholz ◽  
Stanley Perlman ◽  
...  
Keyword(s):  
Middle East ◽  
Pulmonary Infection ◽  
Serum Antibody ◽  
Case Fatality ◽  
Immune Serum ◽  
Middle East Respiratory Syndrome ◽  
Specific Therapy ◽  
Passive Immunotherapy ◽  
Coronavirus Infection ◽  
Kinetics Of

ABSTRACTMiddle East respiratory syndrome (MERS) is a highly lethal pulmonary infection. Serum from convalescent MERS patients may provide some benefit but is not readily available. In contrast, nearly all camels in the Middle East have been infected with MERS-CoV. Here, we show that sera obtained from MERS-immune camels augment the kinetics of MERS-CoV clearance and reduce the severity of pathological changes in infected lungs, with efficacy proportional to the titer of MERS-CoV-neutralizing serum antibody.IMPORTANCEMiddle East respiratory syndrome, caused by a coronavirus, is highly lethal, with a case fatality rate of 35 to 40%. No specific therapy is available, and care is generally supportive. One promising approach is passive administration of sera from convalescent human MERS patients or other animals to exposed or infected patients. The vast majority of, if not all, camels in the Middle East have been infected with MERS-CoV, and some contain high titers of antibody to the virus. Here, we show that this antibody is protective if delivered either prophylactically or therapeutically to mice infected with MERS-CoV, indicating that this may be a useful intervention in infected patients.

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 Middle East Respiratory Syndrome Coronavirus (MERS-CoV): State of the Science

2020 ◽  
Vol 8 (7) ◽  
pp. 991 ◽  
Author(s):  
Ahmed Mostafa ◽  
Ahmed Kandeil ◽  
Mahmoud Shehata ◽  
Rabeh El Shesheny ◽  
Abdallah M. Samy ◽  
...  
Keyword(s):  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Disease Outbreaks ◽  
Case Fatality ◽  
Large Family ◽  
Middle East Respiratory Syndrome ◽  
Current State ◽  
The Common ◽  
Mode Of Transmission ◽  
State Of The Science

Coronaviruses belong to a large family of viruses that can cause disease outbreaks ranging from the common cold to acute respiratory syndrome. Since 2003, three zoonotic members of this family evolved to cross species barriers infecting humans and resulting in relatively high case fatality rates (CFR). Compared to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV, CFR = 10%) and pandemic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, CFR = 6%), the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has scored the highest CFR (approximately 35%). In this review, we systematically summarize the current state of scientific knowledge about MERS-CoV, including virology and origin, epidemiology, zoonotic mode of transmission, and potential therapeutic or prophylactic intervention modalities.

scholarly journals Epidemiology and evolution of Middle East respiratory syndrome coronavirus, 2012–2020

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
An-Ran Zhang ◽  
Wen-Qiang Shi ◽  
Kun Liu ◽  
Xin-Lou Li ◽  
Ming-Jin Liu ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Middle East ◽  
Transportation Network ◽  
Case Fatality ◽  
Middle East Respiratory Syndrome ◽  
World Health ◽  
Spatial Diffusion ◽  
Risk Of Death ◽  
Animal Contact ◽  
History Of

Abstract Background The ongoing transmission of the Middle East respiratory syndrome coronavirus (MERS-CoV) in the Middle East and its expansion to other regions are raising concerns of a potential pandemic. An in-depth analysis about both population and molecular epidemiology of this pathogen is needed. Methods MERS cases reported globally as of June 2020 were collected mainly from World Health Organization official reports, supplemented by other reliable sources. Determinants for case fatality and spatial diffusion of MERS were assessed with Logistic regressions and Cox proportional hazard models, respectively. Phylogenetic and phylogeographic analyses were performed to examine the evolution and migration history of MERS-CoV. Results A total of 2562 confirmed MERS cases with 150 case clusters were reported with a case fatality rate of 32.7% (95% CI: 30.9‒34.6%). Saudi Arabia accounted for 83.6% of the cases. Age of ≥ 65 years old, underlying conditions and ≥ 5 days delay in diagnosis were independent risk factors for death. However, a history of animal contact was associated with a higher risk (adjusted OR = 2.97, 95% CI: 1.10–7.98) among female cases < 65 years but with a lower risk (adjusted OR = 0.31, 95% CI: 0.18–0.51) among male cases ≥ 65 years old. Diffusion of the disease was fastest from its origin in Saudi Arabia to the east, and was primarily driven by the transportation network. The most recent sub-clade C5.1 (since 2013) was associated with non-synonymous mutations and a higher mortality rate. Phylogeographic analyses pointed to Riyadh of Saudi Arabia and Abu Dhabi of the United Arab Emirates as the hubs for both local and international spread of MERS-CoV. Conclusions MERS-CoV remains primarily locally transmitted in the Middle East, with opportunistic exportation to other continents and a potential of causing transmission clusters of human cases. Animal contact is associated with a higher risk of death, but the association differs by age and sex. Transportation network is the leading driver for the spatial diffusion of the disease. These findings how this pathogen spread are helpful for targeting public health surveillance and interventions to control endemics and to prevent a potential pandemic. Graphical abstract

scholarly journals Prevalence of comorbidities in cases of Middle East respiratory syndrome coronavirus: a retrospective study

2018 ◽  
Vol 147 ◽  
Author(s):  
F.Y. Alqahtani ◽  
F.S. Aleanizy ◽  
R. Ali El Hadi Mohamed ◽  
M. S. Alanazi ◽  
N. Mohamed ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Middle East ◽  
Clinical Presentation ◽  
Clinical Manifestations ◽  
Case Fatality ◽  
Middle East Respiratory Syndrome ◽  
Shortness Of Breath ◽  
Life Threatening ◽  
Stage Renal Disease ◽  
End Stage

AbstractThe Middle East respiratory syndrome coronavirus (MERS-CoV) is a life-threatening respiratory disease with a high case fatality rate; however, its risk factors remain unclear. We aimed to explore the influence of demographic factors, clinical manifestations and underlying comorbidities on mortality in MERS-CoV patients. Retrospective chart reviews were performed to identify all laboratory-confirmed cases of MERS-COV infection in Saudi Arabia that were reported to the Ministry of Health of Saudi Arabia between 23 April 2014 and 7 June 2016. Statistical analyses were conducted to assess the effect of sex, age, clinical presentation and comorbidities on mortality from MERS-CoV. A total of 281 confirmed MERS-CoV cases were identified: 167 (59.4%) patients were male and 55 (20%) died. Mortality predominantly occurred among Saudi nationals and older patients and was significantly associated with respiratory failure and shortness of breath. Of the 281 confirmed cases, 160 (56.9%) involved comorbidities, wherein diabetes mellitus, hypertension, ischemic heart disease, congestive heart failure, end-stage renal disease and chronic kidney disease were significantly associated with mortality from MERS-CoV and two or three comorbidities significantly affected the fatality rates from MERS-CoV. The findings of this study show that old age and the existence of underlying comorbidities significantly increase mortality from MERS-CoV.

scholarly journals Improving turnaround time of molecular diagnosis of Middle East respiratory syndrome coronavirus in a hospital in Saudi Arabia

2021 ◽  
Author(s):  
Ali A Rabaan ◽  
Jaffar A Al-Tawfiq
Keyword(s):  
Middle East ◽  
Case Fatality Rate ◽  
Case Fatality ◽  
Turnaround Time ◽  
Middle East Respiratory Syndrome ◽  
Control Measures ◽  
Chain Reaction ◽  
Infection Control Measures ◽  
The Mean ◽  
Polymerase Chain

Abstract Background There have been 2562 laboratory-confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) in 27 countries, with a case fatality rate of 34.5%. Data on the turnaround time (TAT) are lacking. We report TAT for MERS-CoV samples over time. Methods This is a monocentric study and the TAT for the reporting of 2664 MERS-CoV polymerase chain reaction (PCR) results were calculated in hours from the time of the receipt of respiratory samples to the reporting of the results. Results The mean TAT±standard deviation was significantly lower in 2018 compared with previous years (19.25±13.8). The percentage of samples processed within 24 h increased from 42.3% to 73.8% in 2015 and 2018, respectively (p&lt;0.0001). The mean TAT was 19.2 h in 2018 and was significantly lower than previous years. Conclusions The TAT for the MERS-CoV results decreased during the study period. Timely reporting of MERS-CoV PCR results may aid in further enhancing infection control measures.

scholarly journals Taking stock of the first 133 MERS coronavirus cases globally – Is the epidemic changing?

2013 ◽  
Vol 18 (39) ◽  
Author(s):  
P M Penttinen ◽  
K Kaasik-Aaslav ◽  
A Friaux ◽  
A Donachie ◽  
B Sudre ◽  
...  
Keyword(s):  
Middle East ◽  
Sex Ratio ◽  
Case Fatality ◽  
Middle East Respiratory Syndrome ◽  
Nosocomial Transmission ◽  
Fatality Risk ◽  
Time Periods ◽  
Case Fatality Risk

Since June 2012, 133 Middle East respiratory syndrome coronavirus (MERS-CoV) cases have been identified in nine countries. Two time periods in 2013 were compared to identify changes in the epidemiology. The case-fatality risk (CFR) is 45% and is decreasing. Men have a higher CFR (52%) and are over-represented among cases. Thirteen out of 14 known primary cases died. The sex-ratio is more balanced in the latter period. Nosocomial transmission was implied in 26% of the cases.

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