Research articles

Expanded Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) as a Therapeutic Strategy in Managing Critically Ill COVID-19 Patients: The Case for Compassionate Use

Pain physician
Volume 23, 2020, Issue 2, E71-e83

Atluri, S.; Manchikanti, L.; Hirsch, J. A..

Abstract

COVID-19 has affected the United States leading to a national emergency with health care and economic impact, propelling the country into a recession with disrupted lifestyles not seen in recent history. COVID-19 is a serious illness leading to multiple deaths in various countries including the United States. Several million Americans satisfy the Center for Disease Control and Prevention (CDC) criteria for being high risk. Unfortunately, the available supply of medical beds and equipment for mechanical ventilation are much less than is projected to be needed. The World Health Organization (WHO) and multiple agencies led by the CDC in the United States have attempted to organize intensive outbreak investigation programs utilizing appropriate preventive measures, evaluation, and treatment. The clinical spectrum of COVID-19 varies from asymptomatic forms to conditions encompassing multiorgan and systemic manifestations in terms of septic shock, and multiple organ dysfunction (MOD) syndromes. The presently approved treatments are supportive but not curative for the disease. There are multiple treatments being studied. These include vaccines, medications Remdesivir and hydroxychloroquine and potentially combination therapy. Finally, expanded umbilical cord mesenchymal stem cells or (UC-MSCs) may have a role and are being studied. The cure of COVID-19 is essentially dependent on the patients' own immune system. When the immune system is over activated in an attempt to kill the virus, this can lead to the production of a large number of inflammatory factors, resulting in severe cytokine storm. The cytokine storm may induce organ damage followed by the edema, dysfunction of air exchange, acute respiratory distress syndrome (ARDS), acute cardiac injury, and secondary infection, which may lead to death. Thus, at this point, the avoidance of the cytokine storm may be the key for the treatment of HCOV-19 infected patients.In China, where there was limited availability of effective modalities to manage COVID-19 several patients were treated with expanded UC-MSCs. Additionally, the Italian College of Anesthesia, Analgesia, Resuscitation and Intensive Care have reported guidelines to treat coronavirus patients with stem cells in the hope of decreasing the number of patients going to the ICU, and, also relatively quickly getting them out of ICU. In this manuscript, we describe the urgent need for various solutions, pathogenesis of coronavirus and the clinical evidence for treatment of COVID-19 with stem cells. The limited but emerging evidence regarding UC MSC in managing COVID-19 suggests that it might be considered for compassionate use in critically ill patients to reduce morbidity and mortality in the United States. The administration and Coronavirus Task Force might wish to approach the potential of expanded UC-MSCs as an evolutionary therapeutic strategy in managing COVID-19 illness with a 3-pronged approach: If proven safe and effective on a specific and limited basis...1. Minimize regulatory burden by all agencies so that critically ill COVID-19 patients will have access regardless of their financial circumstance.2. Institute appropriate safeguards to avoid negative consequences from unscrupulous actors.3. With proper informed consent from patients or proxy when necessary, and subject to accumulation of data in that cohort, allow the procedure to be initiated in critically ill patients who are not responding to conventional therapies.KEY WORDS: Coronavirus, COVID-19, cytokine storm, multiorgan failure, expanded umbilical cord mesenchymal stem cells.

Keywords

Coronavirus, COVID-19, cytokine storm, multiorgan failure, expanded umbilical cord mesenchymal stem cells

Role of changes in SARS-CoV-2 spike protein in the interaction with the human ACE2 receptor: An in silico analysis

EXCLI journal
Volume 19, March 2020, pp 410-417

Ortega, J. T.; Serrano, M. L.; Pujol, F. H.; Rangel, H. R.

Abstract

Many human viral diseases are a consequence of a zoonotic event. Some of the diseases caused by these zoonotic events have affected millions of people around the world, some of which have resulted in high rates of morbidity/mortality in humans. Changes in the viral proteins that function as ligands of the host receptor may promote the spillover between species. The most recent of these zoonotic events that have caused an ongoing epidemic of high magnitude is the Covid-19 epidemics caused by SARS-CoV-2. The aim of this study was to determine the mutation(s) in the sequence of the spike protein of the SARS-CoV-2 that might be favoring human to human transmission. An in silico approach was performed, and changes were detected in the S1 subunit of the receptor-binding domain of spike. The observed changes have significant effect on SARS-CoV-2 spike/ACE2 interaction and produce a reduction in the binding energy, compared to the one of the Bat-CoV to this receptor. The data presented in this study suggest a higher affinity of the SARS-Cov-2 spike protein to the human ACE2 receptor, compared to the one of Bat-CoV spike and ACE2. This could be the cause of the rapid viral spread of SARS-CoV-2 in humans.

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Keywords

Comparative study, RCT; Clinical aspects, diagnosis, treatment

Potential therapeutic options for coronavirus disease 2019: using knowledge of past outbreaks to guide future treatment

Chinese medical journal

Lin, J.; Ouyang, J.; Peng, X. R.; Isnard, S.; Fombuena, B.; Routy, J. P.; Chen, Y. K.

Introduction

In December 2019, initial cases of the novel coronavirus (2019-nCov) infection, termed Coronavirus Disease 2019 (COVID-19), were first reported in Wuhan, China. In humans, infections with the human coronavirus 229E, OC43, NL63 and HKU1 usually result in mild, self-limiting upper respiratory tract infections. However, other variants have rapid transmission rates and can cause severe respiratory syndrome and death. These variants include severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the current 2019-nCov…

Keywords

By Comparative study, RCT; Normative guidance; Clinical aspects, diagnosis, treatment; Epidemiology

Unrevealing sequence and structural features of novel coronavirus using in silico approaches: The main protease as molecular target

EXCLI journal
Volume 19, March 2020, pp 400-409

Ortega, J. T.; Serrano, M. L.; Pujol, F. H.; Rangel, H. R.

Abstract

Direct-acting antivirals are effective tools to control viral infections. SARS-CoV-2 is a coronavirus associated with the epidemiological outbreak in late 2019. Previous reports showed that HIV-1 protease inhibitors could block SARS-CoV main protease. Based on that and using an in silico approach, we evaluated SARS-CoV-2 main protease as a target for HIV-1 protease inhibitors to reveal the structural features related to their antiviral effect. Our results showed that several HIV inhibitors such as lopinavir, ritonavir, and saquinavir produce strong interaction with the active site of SARS-CoV-2 main protease. Furthermore, broad library protease inhibitors obtained from PubChem and ZINC (www.zinc.docking.org) were evaluated. Our analysis revealed 20 compounds that could be clustered into three groups based on their chemical features. Then, these structures could serve as leading compounds to develop a series of derivatives optimizing their activity against SARS-CoV-2 and other coronaviruses. Altogether, the results presented in this work contribute to gain a deep understanding of the molecular pharmacology of SARS-CoV-2 treatment and validate the use of protease inhibitors against SARS-CoV-2.

Keywords

Clinical aspects, diagnosis, treatment

Can chlorine dioxide prevent the spreading of coronavirus or other viral infections? Medical hypotheses

Physiology international
Pages 1-11

Kaly-Kullai, K.; Wittmann, M.; Noszticzius, Z.; Rosivall, L.

Introduction

Viruses have caused many epidemics throughout human history. The novel coronavirus is just the latest example. A new viral outbreak can be unpredictable, and development of specific defense tools and countermeasures against the new virus remains time-consuming even in today's era of modern medical science and technology. In the lack of effective and specific medication or vaccination, it would be desirable to have a nonspecific protocol or substance to render the virus inactive, a substance/protocol, which could be applied whenever a new viral outbreak occurs. This is especially important in cases when the emerging new virus is as infectious as SARS-CoV-2

Keywords

COVID-19, SARS-CoV-2, Medication

Climate factors and incidence of Middle East respiratory syndrome coronavirus

Journal of Infection and Public Health
ARTICLE IN PRESS

Asmaa Altamimi, Anwar E. Ahmed

Abstract

Background

Our understanding of climate factors and their links to the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) outbreaks is incomplete. This study aimed to estimate the monthly incidence of MERS-CoV cases and to investigate their correlation to climate factors.

Methods

The study used aggregated monthly MERS-CoV cases that reported to the Saudi Center for Disease Prevention and Control from the Riyadh Region between November 1, 2012 and December 31, 2018. Data on the meteorological situation throughout the study period was calculated based on Google reports on the Riyadh Region (24.7136 °N, 46.6753 °E). The Poisson regression was used to estimate the incidence rate ratio (IRR) and its 95% confidence intervals (CI) for each climate factor.

Results

A total of 712 MERS-CoV cases were included in the analysis (mean age 54.2 ± 9.9 years), and more than half (404) (56.1%) MERS-CoV cases were diagnosed during a five-month period from April to August. The highest peak timing positioned in August 2015, followed by April 2014, June 2017, March 2015, and June 2016. High temperatures (IRR = 1.054, 95% CI: 1.043–1.065) and a high ultraviolet index (IRR = 1.401, 95% CI: 1.331–1.475) were correlated with a higher incidence of MERS-CoV cases. However, low relative humidity (IRR = 0.956, 95% CI: 0.948–0.964) and low wind speed (IRR = 0.945, 95% CI: 0.912–0.979) were correlated with a lower incidence of MERS-CoV cases.

Conclusion

The novel coronavirus, MERS-CoV, is influenced by climate conditions with increasing incidence between April and August. High temperature, high ultraviolet index, low wind speed, and low relative humidity are contributors to increased MERS-CoV cases. The climate factors must be evaluated in hospitals and community settings and integrated into guidelines to serve as source of control measures to prevent and eliminate the risk of infection.

Keywords

Weather conditions, Meteorological factors, MERS-CoV

Nucleocapsid Proteins From Other Swine Enteric Coronaviruses Differentially Modulate PEDV Replication

Virology
Volume 540, 15 January 2020, Pages 45-56

Sungsuwan, S.; Jongkaewwattana, A.; Jaru-Ampornpan, P.

Abstract

Porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV) and porcine deltacoronavirus (PDCoV) share tropism for swine intestinal epithelial cells. Whether mixing of viral components during co-infection alters pathogenic outcomes or viral replication is not known. In this study, we investigated how different coronavirus nucleocapsid (CoV N) proteins interact and affect PEDV replication. We found that PDCoV N and TGEV N can competitively interact with PEDV N. However, the presence of PDCoV or TGEV N led to very different outcomes on PEDV replication. While PDCoV N significantly suppresses PEDV replication, overexpression of TGEV N, like that of PEDV N, increases production of PEDV RNA and virions. Despite partial interchangeability in nucleocapsid oligomerization and viral RNA synthesis, endogenous PEDV N cannot be replaced in the production of infectious PEDV particles. Results from this study give insights into functional compatibilities and evolutionary relationship between CoV viral proteins during viral co-infection and co-evolution.

Keywords

Porcine epidemic diarrhea virus, Swine coronavirus, Nucleocapsid protein

Characterization And Evolution Of The Coronavirus Porcine Epidemic Diarrhoea Virus HLJBY Isolated In China

Transboundary and Emerging Diseases

Huan, ChangChao; Pan, HaoChun; Fu, SiYao; Xu, WeiYin; Gao, QingQing; Wang, XiaoBo; Gao, Song; Chen, ChangHai; Liu, XiuFan

Abstract

A strain of porcine epidemic diarrhoea virus (PEDV), namely HLJBY, was isolated in Heilongjiang province, China. To provide insight into the understanding of the phylogenetic and the current epidemiological status of PEDV, PEDV HLJBY was compared with CV777 and other PEDV strains deposited in the GenBank. The homology between the entire genomic nucleotide sequences of PEDV HLJBY and CV777 was 97.7%. The homology of M gene was the highest (99.0%). However, the homology of ORF3 gene was 97.7%, and protein of ORF3 was 90.1%. In addition, HLJBY showed the highest nucleotide identity (99.9%) with PEDV-SX/China/2017 strain and lowest similarity (91.2%) to PEDV/Belgorod/dom/2008 strain. We analysed the changes in S gene and its protein of PEDV HLJBY with 65 historic PEDV strains. The highest nucleotide identity was 99.9% compared with PEDV-SX/China/2017 strain, and the lowest nucleotide identity was 60.0% compared with PEDV/Belgorod/dom/2008 strain. The length of deduced amino acid sequences of S proteins varied from 1,372 to 1,390 amino acids (aa). Compared with most aa sequences of S proteins, HLJBY exhibited 5 aa deletions (position 55, 59-61, 144). Analysis and comparison of open reading frame 3 (ORF3) proteins between HLJBY strain and other PEDV strains were also focused in this study. We revealed that the length of deduced amino acid sequences of ORF3 proteins was 80-224 aa among tested strains and the identity of HLJBY ORF3 amino acids with other PEDV strains was 71.4%-98.9%. ORF3 protein of both HLJBY strain and PEDV-SX/China/2017 strain consists of 91 aa, with 133 aa deletions at their C' end in relation to the other tested PEDV strains. The phylogenetic tree based on different proteins or genes resulted in different phylogenetic groups. For pathogenicity evaluation of PEDV HLJBY strain, colostrum deprivation piglets were challenged with PEDV HLJBY, and PEDV reference strain CV777 as a control, the results showed that animals challenged with either of these PEDV strains developed diarrhoea, and histopathological examination of small intestines of challenged animals showed acute viral enteritis with villous atrophy in either PEDV HLJBY-P10 or PEDV CV777-P8 inoculated piglets.

Keywords

genomic sequence, HLJBY strain, open reading frame 3, phylogenetic analysis, porcine epidemic diarrhoea virus, S protein

Changes in infection control policies and advancing infection control advanced practice nurse education in the Republic of Korea

AJIC - American Journal of Infection Control
Volume 48, Issue 2, Pages 204-206

Choi, J. S.; Kim, K. M..

Abstract

After the Middle East respiratory syndrome outbreak of 2015, the Korean government became the payer for infection control (IC) and prevention when hospitals developed IC offices and appointed IC doctors and IC advanced practice nurses. The goal was to enhance IC for all hospitalized patients to prevent the occurrence and spread of infection among them. Measures resulted in increased demand for IC personnel, especially IC advanced practice nurses. This study addressed changes in Korea's IC policies and their impact on the IC advanced practice nursing education program.

Keywords

Infection control, Nurse, Education

A high-throughput inhibition assay to study MERS-CoV antibody interactions using image cytometry

Journal of Virological Methods
Volume 265, March 2019, Pages 77-83

Osnat Rosen, Leo Li-Ying Chan, Olubukola M. Abiona, Portia Gough, Lingshu Wang, Wei Shi, Yi Zhang, Nianshuang Wang, Wing-Pui Kong, Jason S. McLellan, Barney S. Graham, Kizzmekia S. Corbett

Abstract

The emergence of new pathogens, such as Middle East respiratory syndrome coronavirus (MERS-CoV), poses serious challenges to global public health and highlights the urgent need for methods to rapidly identify and characterize potential therapeutic or prevention options, such as neutralizing antibodies. Spike (S) proteins are present on the surface of MERS-CoV virions and mediate viral entry. S is the primary target for MERS-CoV vaccine and antibody development, and it has become increasingly important to understand MERS-CoV antibody binding specificity and function. Commonly used serological methods like ELISA, biolayer interferometry, and flow cytometry are informative, but limited. Here, we demonstrate a high-throughput protein binding inhibition assay using image cytometry. The image cytometry-based high-throughput screening method was developed by selecting a cell type with high DPP4 expression and defining optimal seeding density and protein binding conditions. The ability of monoclonal antibodies to inhibit MERS-CoV S binding was then tested. Binding inhibition results were comparable with those described in previous literature for MERS-CoV spike monomer and showed similar patterns as neutralization results. The coefficient of variation (CV) of our cell-based assay was <10%. The proposed image cytometry method provides an efficient approach for characterizing potential therapeutic antibodies for combating MERS-CoV that compares favorably with current methods. The ability to rapidly determine direct antibody binding to host cells in a high-throughput manner can be applied to study other pathogen-antibody interactions and thus can impact future research on viral pathogens.

Keywords

MERS-CoV, Antibody binding, Inhibition assay, Antibody neutralization, Image cytometry, Celigo

Effect of interferon alpha and cyclosporine treatment separately and in combination on Middle East Respiratory Syndrome Coronavirus (MERS-CoV) replication in a human in-vitro and ex-vivo culture model

Antiviral Research
Volume 155, July 2018, Pages 89-96

H. S. Li, Denise I. T. Kuok, M. C. Cheung, Mandy M. T. Ng, K. C.nNg, Kenrie P.Y.Hui, J. S.mMalik Peiris, Michael C. W. Chan John M. Nicholls

Abstract

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has emerged as a coronavirus infection of humans in the past 5 years. Though confined to certain geographical regions of the world, infection has been associated with a case fatality rate of 35%, and this mortality may be higher in ventilated patients. As there are few readily available animal models that accurately mimic human disease, it has been a challenge to ethically determine what optimum treatment strategies can be used for this disease. We used in-vitro and human ex-vivo explant cultures to investigate the effect of two immunomodulatory agents, interferon alpha and cyclosporine, singly and in combination, on MERS-CoV replication. In both culture systems the combined treatment was more effective than either agent used alone in reducing MERS-CoV replication. PCR SuperArray analysis showed that the reduction of virus replication was associated with a greater induction of interferon stimulated genes. As these therapeutic agents are already licensed for clinical use, it may be relevant to investigate their use for therapy of human MERS-CoV infection.

Keywords

Middle East Respiratory Syndrome Coronavirus (MERS-CoV)Type I interferon, Cyclosporine, Ex vivo explants

Adaptive evolution influences the infectious dose of MERS-CoV necessary to achieve severe respiratory disease

Virology
Volume 517, April 2018, Pages 98-107

Madeline G. Douglas, Jacob F. Kocher, Trevor Scobey, Ralph S. Baric, Adam S. Cockrell

Abstract

We recently established a mouse model (288–330+/+) that developed acute respiratory disease resembling human pathology following infection with a high dose (5 × 106 PFU) of mouse-adapted MERS-CoV (icMERSma1). Although this high dose conferred fatal respiratory disease in mice, achieving similar pathology at lower viral doses may more closely reflect naturally acquired infections. Through continued adaptive evolution of icMERSma1 we generated a novel mouse-adapted MERS-CoV (maM35c4) capable of achieving severe respiratory disease at doses between 103 and 105 PFU. Novel mutations were identified in the maM35c4 genome that may be responsible for eliciting etiologies of acute respiratory distress syndrome at 10–1000 fold lower viral doses. Importantly, comparative genetics of the two mouse-adapted MERS strains allowed us to identify specific mutations that remained fixed through an additional 20 cycles of adaptive evolution. Our data indicate that the extent of MERS-CoV adaptation determines the minimal infectious dose required to achieve severe respiratory disease.

Keywords

Coronavirus, MERS-CoV, Middle East respiratory syndrome, Respiratory disease, Acute respiratory distress syndrome, Spike protein

Structural insights of a self-assembling 9-residue peptide from the C-terminal tail of the SARS corona virus E-protein in DPC and SDS micelles: A combined high and low resolution spectroscopic study

Biochimica et Biophysica Acta (BBA) - Biomembranes
Volume 1860, Issue 2, February 2018, Pages 335-346

Anirban Ghosh, Dipita Bhattacharyya, Anirban Bhunia

Abstract

In recent years, several studies based on the interaction of self-assembling short peptides derived from viroporins with model membranes, have improved our understanding of the molecular mechanism of corona virus (CoV) infection under physiological conditions. In this study, we have characterized the mechanism of membrane interaction of a short, 9-residue peptide TK9 (T55VYVYSRVK63) that had been derived from the carboxyl terminal of the Severe Acute Respiratory Syndrome (SARS) corona virus (SARS CoV) envelope (E) protein. The peptide has been studied for its physical changes in the presence of both zwitterionic DPC and negatively charged SDS model membrane micelles, respectively, with the help of a battery of biophysical techniques including two-dimensional solution state NMR spectroscopy. Interestingly, in both micellar environments, TK9 adopted an alpha helical conformation; however, the helical propensities were much higher in the case of DPC compared to those of SDS micelle, suggesting that TK9 has more specificity towards eukaryotic cell membrane than the bacterial cell membrane. The orientation of the peptide TK9 also varies in the different micellar environments. The peptide's affinity was further manifested by its pronounced membrane disruption ability towards the mammalian compared to the bacterial membrane mimic. Collectively, the in-depth structural information on the interaction of TK9 with different membrane environments explains the host specificity and membrane orientation owing to subsequent membrane disruption implicated in the viral pathogenesis.

Keywords

NMR, SARS CoV, Micelle, NOESY, Paramagnetic relaxation

SARS-CoV-Encoded Small RNAs Contribute to Infection-Associated Lung Pathology

Cell Host and Microbes
Volume 21, Issue 3, 8 March 2017, Pages 344-355

Lucía Morales, Juan Carlos Oliveros, Raúl Fernandez-Delgado, Benjamin Robertten Oever, Luis Enjuanes, and Isabel Sola

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV) causes lethal disease in humans, which is characterized by exacerbated inflammatory response and extensive lung pathology. To address the relevance of small non-coding RNAs in SARS-CoV pathology, we deep sequenced RNAs from the lungs of infected mice and discovered three 18–22 nt small viral RNAs (svRNAs). The three svRNAs were derived from the nsp3 (svRNA-nsp3.1 and -nsp3.2) and N (svRNA-N) genomic regions of SARS-CoV. Biogenesis of CoV svRNAs was RNase III, cell type, and host species independent, but it was dependent on the extent of viral replication. Antagomir-mediated inhibition of svRNA-N significantly reduced in vivo lung pathology and pro-inflammatory cytokine expression. Taken together, these data indicate that svRNAs contribute to SARS-CoV pathogenesis and highlight the potential of svRNA-N antagomirs as antivirals.

Keywords

coronavirus, SARS-CoV, small viral RNAs, virus-host interaction, lung inflammatory pathology, antagomirs, deep sequencing, non-coding RNAs, innate immune response, antiviral

Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, 2015: epidemiology, characteristics and public health implications

Journal of Hospital Infection
Volume 95, Issue 2, February 2017, Pages 207-213

K. H. Kim, T. E. Tandi, J. W. Choi, J. M. Moon, M. S. Kimab

Summary

Since the first case of Middle East respiratory syndrome coronavirus (MERS-CoV) in South Korea was reported on 20th May 2015, there have been 186 confirmed cases, 38 deaths and 16,752 suspected cases. Previously published research on South Korea's MERS outbreak was limited to the early stages, when few data were available. Now that the outbreak has ended, albeit unofficially, a more comprehensive review is appropriate.

Methods

Data were obtained through the MERS portal by the Ministry for Health and Welfare (MOHW) and Korea Centres for Disease Control and Prevention, press releases by MOHW, and reports by the MERS Policy Committee of the Korean Medical Association. Cases were analysed for general characteristics, exposure source, timeline and infection generation. Sex, age and underlying diseases were analysed for the 38 deaths.

Findings

Beginning with the index case that infected 28 others, an in-depth analysis was conducted. The average age was 55 years, which was a little higher than the global average of 50 years. As in most other countries, more men than women were affected. The case fatality rate was 19.9%, which was lower than the global rate of 38.7% and the rate in Saudi Arabia (36.5%). In total, 184 patients were infected nosocomially and there were no community-acquired infections. The main underlying diseases were respiratory diseases, cancer and hypertension. The main contributors to the outbreak were late diagnosis, quarantine failure of ‘super spreaders’, familial care-giving and visiting, non-disclosure by patients, poor communication by the South Korean Government, inadequate hospital infection management, and ‘doctor shopping’. The outbreak was entirely nosocomial, and was largely attributable to infection management and policy failures, rather than biomedical factors.

Keywords

MERS-CoV outbreak, Epidemiology, Public health, South Korea

Use of the Human Coronavirus 2012 (MERS) GeneSig kit for MERS-CoV detection

Gene Reports
Volume 4, September 2016, Pages 67-69

Rouba Hoteit, Dina Shammaa, Rami Mahfouz

Abstract

Introduction

Mortality due to MERS-CoV infection is common especially among immunocompromised patients. The pathogenesis and the transmission mode of this virus are still not well understood. The name of the virus is derived from the area of its appearance and the genomic sequence that was used in the development of qRT-PCR assays for MERS-CoV detection was retrieved from the first detected case isolate. The employed assays target various regions including the area upstream of the envelope gene (upE) that is used for screening and the open reading frames (ORF) 1a and 1b used for confirmation.

Aim

This study assesses the use of a MERS-CoV specific assay for screening of respiratory samples in anticipation of the possible spread of the virus in the region.

Methods

46 respiratory specimens were tested using the qualitative one-step qRT-PCR GeneSig Human Coronavirus 2012 (MERS) kit (PrimerDesign™).

Results

Out of the 46 tested samples, 45 were negative for MERS-CoV and one sample was found MERS-CoV positive.

Conclusion

The GeneSig Human Coronavirus 2012 (MERS) kit is very useful for the screening of suspected respiratory cases in the Middle East area as well as other regions.

Keywords

MERS-CoV, Lebanon, GeneSig kit


Identification, synthesis and evaluation of SARS-CoV and MERS-CoV 3C-like protease inhibitors

Bioorganic & Medicinal Chemistry
Volume 24, Issue 13, 1 July 2016, Pages 3035-3042

Vathan Kumar, Kian-Pin Tan, Ying-Ming Wang, Sheng-Wei Lin, Po-Huang Liang

Abstract

Severe acute respiratory syndrome (SARS) led to a life-threatening form of atypical pneumonia in late 2002. Following that, Middle East Respiratory Syndrome (MERS-CoV) has recently emerged, killing about 36% of patients infected globally, mainly in Saudi Arabia and South Korea. Based on a scaffold we reported for inhibiting neuraminidase (NA), we synthesized the analogues and identified compounds with low micromolar inhibitory activity against 3CLpro of SARS-CoV and MERS-CoV. Docking studies show that a carboxylate present at either R1 or R4 destabilizes the oxyanion hole in the 3CLpro. Interestingly, 3f, 3g and 3m could inhibit both NA and 3CLpro and serve as a starting point to develop broad-spectrum antiviral agents.

Keywords

MERS-CoV, SARS-Cov, 3CLpro, Coronavirus, Pyrazolone

MERS-CoV: Middle East respiratory syndrome corona virus: Can radiology be of help? Initial single center experience

The Egyptian Journal of Radiology and Nuclear Medicine
Volume 47, Issue 1, March 2016, Pages 95-106

Ahmed Hamimi

Abstract

Human infection with a novel coronavirus named Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia and the Middle East in September, 2012. The aim of this study was to establish the most pathognomonic radiological sign(s) to diagnose MERS CoV.

Patients and methods

This is a retrospective descriptive study. All patients were subjected to serial X-ray. High resolution non-contrast CT chest was also obtained for 10 patients. The scans were reviewed for findings including consolidation, ground-glass opacities, nodules, reticular opacities and hilar and mediastinal adenopathy.

Results

A total of 12 patients were included in our study with prevalence of males (2:1) with ages ranging between 18 and 76 years having an average age of 36 ± 2 years. The outcome of these patients was as follows: 6 were treated with average hospital stay ranging between 21 and 35 days, one case died after 14 days, and 5 cases were transferred to Central Governmental hospital according the local authority rules.

Conclusions

MERS CoV virus may have a specific pattern in chest X-ray and CT developing a single or multiple opacities progressing into a widespread multifocal bilateral patches of ground glass opacities or confluent consolidation resembling organizing pneumonia.

Keywords

MERS-CoV, CT, Chest X-ray, Ground glass, Organizing pneumonia

Receptor-binding domain-based subunit vaccines against MERS-CoV

Virus Research
Volume 202, 16 April 2015, Pages 151-159

Naru Zhang, Jian Tang, Lu Lu, Shibo Jiang, Lanying Du

Abstract

Development of effective vaccines, in particular, subunit-based vaccines, against emerging Middle East respiratory syndrome (MERS) caused by the MERS coronavirus (MERS-CoV) will provide the safest means of preventing the continuous spread of MERS in humans and camels. This review briefly describes the structure of the MERS-CoV spike (S) protein and its receptor-binding domain (RBD), discusses the current status of MERS vaccine development and illustrates the strategies used to develop RBD-based subunit vaccines against MERS. It also summarizes currently available animal models for MERS-CoV and proposes a future direction for MERS vaccines. Taken together, this review will assist researchers working to develop effective and safe subunit vaccines against MERS-CoV and any other emerging coronaviruses that might cause future pandemics.

Keywords

Middle East respiratory syndrome coronavirus, MERS-CoV, Receptor-binding domain, Subunit vaccines