#Pharmacologic #Treatments and #Supportive Care for #MERS #Coronavirus (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Pharmacologic Treatments and Supportive Care for Middle East Respiratory Syndrome

Taylor Kain, Patrick J. Lindsay, Neill K.J. Adhikari, Yaseen M. Arabi, Maria D. Van Kerkhove, and Robert A. Fowler

Author affiliations: University of Toronto, Toronto, Ontario, Canada (T. Kain, P.J. Lindsay, N.K.J. Adhikari, R.A. Fowler); Harvard University, Boston, Massachusetts, USA (P.J. Lindsay); Sunnybrook Health Sciences Center, Toronto (N.K.J. Adhikari, R.A. Fowler); King Saud Bin Abdulaziz University for Health Center, Riyadh, Saudi Arabia (Y.M. Arabi); King Abdullah International Medical Research Center, Riyadh (Y.M. Arabi); World Health Organization, Geneva, Switzerland (M.D. Van Kerkhove)

 

Abstract

Available animal and cell line models have suggested that specific therapeutics might be effective in treating Middle East respiratory syndrome (MERS). We conducted a systematic review of evidence for treatment with pharmacologic and supportive therapies. We developed a protocol and searched 5 databases for studies describing treatment of MERS and deaths in MERS patients. Risk of bias (RoB) was assessed by using ROBINS-I tool. We retrieved 3,660 unique citations; 20 observational studies met eligibility, and we studied 13 therapies. Most studies were at serious or critical RoB; no studies were at low RoB. One study, at moderate RoB, showed reduced mortality rates in severe MERS patients with extracorporeal membrane oxygenation; no other studies showed a significant lifesaving benefit to any treatment. The existing literature on treatments for MERS is observational and at moderate to critical RoB. Clinical trials are needed to guide treatment decisions.

Keywords: MERS-CoV; ECMO.

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#Tilorone: A Broad-Spectrum #Antiviral For Emerging Viruses (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Tilorone: A Broad-Spectrum Antiviral For Emerging Viruses

Sean Ekins, Peter B. Madrid

DOI: 10.1128/AAC.00440-20

 

ABSTRACT

Tilorone is a 50-year-old synthetic small-molecule compound with antiviral activity that is proposed to induce interferon after oral administration. This drug is used as a broad-spectrum antiviral in several countries of the Russian Federation. We have recently described activity in vitro and in vivo against the Ebola Virus. After a broad screening of additional viruses, we now describe in vitro activity against Chikungunya virus (CHIK) and Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV).

Copyright © 2020 American Society for Microbiology. All Rights Reserved.

Keywords: MERS-CoV; Antivirals; Tilorone.

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#Comparison of #Pathological Changes and #Pathogenic Mechanisms Caused by #H1N1 Influenza Virus, HPAI #H5N1, #SARS-CoV, #MERS-CoV and 2019-nCoV #Coronavirus (Zhonghua Bing Li Xue Za Zhi, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Zhonghua Bing Li Xue Za Zhi, 40 (0), E006 2020 Mar 16 [Online ahead of print]

[Comparison of Pathological Changes and Pathogenic Mechanisms Caused by H1N1 Influenza Virus, Highly Pathogenic H5N1 Avian Influenza Virus, SARS-CoV, MERS-CoV and 2019-nCoV Coronavirus]

[Article in Chinese]

M Liu 1, R E Feng 2, Q Li 3, H K Zhang 1, Y G Wang 1

Affiliations: 1 Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China. 2 Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. 3 Shunyi Hospital of Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 101300, China.

PMID: 32174094 DOI: 10.3760/cma.j.cn112151-20200301-00155

 

Abstract

The rapid development of the new coronavirus pneumonia epidemic in Wuhan, China, has caused severe impact on the country, but so far, little is known about the pathological changes and pathogenesis of the new coronavirus pneumonia. This article summarizes the pathological changes of severe influenza virus H1N1, highly pathogenic avian influenza virus H5N1, SARS-CoV, MERS-CoV, and 2019-nCoV coronavirus that cause major outbreaks of viral infectious diseases. The autopsy lung tissues are diffuse. Alveolar damage (DAD), but pathological manifestations caused by different viruses are different. Severe influenza virus 2009 H1N1 virus binds to receptors α-2,6-SA and α-2,3-SA, except for DAD lesions It is often accompanied by inflammatory lesions of the upper respiratory tract, trachea, bronchi and bronchioles, and is more likely to be complicated by bacterial infection. The highly pathogenic avian influenza virus H5N1 mainly binds α-2,3-SA receptors, mainly involving alveolar epithelium and bronchioles. Rarely, upper respiratory tract and trachea and bronchial lesions are often associated with focal pulmonary hemorrhage and lung tissue necrosis. Mechanization and fibrosis are rare. SARS-CoV enters cells by binding to angiotensin-converting enzyme 2 (ACE2), and the lesions are related to the course of disease. The DAD exudation period is generally seen in patients who die within 10 to 14 days. Patients with a disease course of more than 10 days showed mechanized DAD, often accompanied by occlusive bronchiolitis with organic pneumonia-like changes and significant multinucleated giant cells in the alveolar cavity. In patients with SARS-CoV and H5N1 infection, lymphocyte depletion in the spleen and lymph nodes, acute tubular necrosis, and hemophagocytic cells in the bone marrow were seen in the extrapulmonary organs.

Keywords: SARS-CoV-2; SARS-CoV; H1N1pdm09; H5N1.

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From #SARS and #MERS CoVs to SARS-CoV-2: Moving Toward More Biased #Codon Usage in Viral Structural and Non-Structural Genes (J Med Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Med Virol 2020 Mar 11 [Online ahead of print]

From SARS and MERS CoVs to SARS-CoV-2: Moving Toward More Biased Codon Usage in Viral Structural and Non-Structural Genes

Mahmoud Kandeel 1 2, Abdel Azim Ibrahim 3 4, Mahmoud Fayez 5 6, Mohammed Al-Nazawi 1

Affiliations: 1 Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-hofuf, Al-ahsa, Saudi Arabia. 2 Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelshikh University, Kafrelshikh, Egypt. 3 Department of Pathology, College of Veterinary Medicine, King Faisal University, Al-hofuf, Al-ahsa, Saudi Arabia. 4 Department of Pathology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt. 5 Al Ahsa Veterinary Diagnostic Laboratory, Ministry of Agriculture, Al-Ahsa, Kingdom of Saudi Arabia. 6 Veterinary Serum and Vaccine Institute, Dokki, Cairo, Egypt.

PMID: 32159237 DOI: 10.1002/jmv.25754

 

Abstract

Background:

SARS-CoV-2 is an emerging disease with fatal outcomes. In this study, a fundamental knowledge gap question is to be resolved by evaluating the differences in biological and pathogenic aspects of SARS-CoV-2 and the changes in SARS-CoV-2 in comparison with the two prior major COV epidemics, SARS and MERS coronaviruses.

Methods:

The genome composition, nucleotides analysis, codon usage indices, relative synonymous codons usage (RESU) and effective number of codons (ENc) were analysed in the four structural genes; Spike (S), Envelope (E), membrane (M), and Nucleocapsid (N) genes, and two of the most important non-structural genes comprising RNA-dependent RNA polymerase (RdRP) and main protease (Mpro) of SARS-CoV-2, Beta-CoV from pangolins, bat SARS, MERS and SARS CoVs. These genes include Spike (S), nucleocapsid (N), Envelop(E) and membrane (M) genes.

Results:

SARS-CoV-2 prefers pyrimidine rich codons to purines. Most high-frequency codons were ending with A or T, while the low frequency and rare codons were ending with G or C. SARS-CoV-2 structural proteins showed 5-20 lower ENc values, compared with SARS, bat SARS and MERS CoVs. This implies higher codon bias and higher gene expression efficiency of SARS-CoV-2 structural proteins. SARS-CoV-2 encoded the highest number of over biased and negatively biased codons. Pangolin Beta-CoV showed little differences with SARS-CoV-2 ENc values, compared with SARS, bat SARS and MERS CoV.

Conclusion:

Extreme bias and lower ENc values of SARS-CoV-2, especially in Spike, Envelope and Mpro genes, are suggestive for higher gene expression efficiency, compared with SARS, bat SARS and MERS CoVs. This article is protected by copyright. All rights reserved.

Keywords: COVID-19; Codon bias.; MERS CoV; Preferred codons; SARS-CoV-2; non-structural protein.

This article is protected by copyright. All rights reserved.

Keywords: SARS-CoV-2; COVID-19; MERS-CoV.

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#Seroprevalence of #MERS #Coronavirus in #Dromedaries and Their #Traders in Upper #Egypt (J Infect Dev Ctries., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Infect Dev Ctries, 14 (2), 191-198 2020 Feb 29

Seroprevalence of Middle East Respiratory Syndrome Corona Virus in Dromedaries and Their Traders in Upper Egypt

Amal Sm Sayed 1, Safaa S Malek 2, Mostafa Fn Abushahba 3

Affiliations: 1 Department of Zoonoses, Faculty of Veterinary Medicine, Assiut University, Asyut, Egypt. amalsayed73@yahoo.com. 2 Department of Animal Medicine, Faculty of Veterinary Medicine, Assiut University, Asyut, Egypt. safaamalek80@aun.edu.eg. 3 Department of Zoonoses, Faculty of Veterinary Medicine, Assiut University, Asyut, Egypt. mateya@aun.edu.eg.

PMID: 32146454 DOI: 10.3855/jidc.10862

 

Abstract

Introduction:

Camel trade in Egypt depends mainly on importation. Seemingly healthy imported camels are responsible for the ingress of serious diseases into Egypt. A striking example of this concerning public health globally is the Middle East respiratory coronavirus (MERS-CoV) which causes case fatalities of over 34%. Here, we determined the seroepidemiological situation of the MERS-CoV in imported camels and their traders in Upper Egypt.

Methodology:

Sera of sixty-three dromedaries and twenty-eight camel traders were recruited (January 2015-December 2016). The age, gender, and sampling locality of each sampled camel and human were obtained. Semi-quantitative anti-MERS-CoV IgG ELISAs which utilize the purified spike protein domain S1 antigen of MERS coronavirus (MERS-CoV S1) were used to detect specific IgG antibodies against the virus.

Results:

The data showed that 58.73% of imported camels and 25% of traders had antibodies specific to MERS-CoV. Interestingly, like seroreactive camels, all seropositive humans were apparently healthy without any history of developing severe respiratory disease in the 14 days prior to sampling. Having specific antibodies among the examined camel sera was significantly different (P < 0.0001) in relation to various sampling localities, gender and age groups. In contrast, the seropositivity rate of MERS-CoV IgG in humans did not differ significantly by any of the studied factors.

Conclusions:

The current study provides the first serological evidence of occupational exposure of humans to MERS-CoV in Africa. Additionally, it reports that imported camels could be implicated in introducing MERS-CoV into Egypt. Accordingly, application of strict control measures to camel importation is a priority.

Keywords: Dromedary camels; ELISA; MERS-CoV; zoonosis.

Copyright (c) 2020 Amal Sayed, Safaa Malek, Mostafa Abushahba.

Conflict of interest statement No Conflict of Interest is declared

Keywords: MERS-CoV; Camels; Human; Egypt; Serology.

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The #Antiviral Compound #Remdesivir Potently Inhibits #RNA-dependent RNA #Polymerase From #MERS #Coronavirus (J Biol Chem., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Biol Chem  2020 Feb 24 [Online ahead of print]

The Antiviral Compound Remdesivir Potently Inhibits RNA-dependent RNA Polymerase From Middle East Respiratory Syndrome Coronavirus

Calvin J Gordon 1, Egor P Tchesnokov 1, Joy Y Feng 2, Danielle P Porter 3, Matthias Gotte 4

Affiliations: 1 University of Alberta, Canada. 2 Biology, Gilead Sciences, United States. 3 Gilead, United States. 4 Medical Microbiology and Immunology, University of Alberta, Canada.

PMID: 32094225 DOI: 10.1074/jbc.AC120.013056

 

Abstract

Antiviral drugs for managing infections with human coronaviruses are not yet approved, posing a serious challenge to current global efforts aimed at containing the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Remdesivir (RDV) is an investigational compound with a broad spectrum of antiviral activities against RNA viruses, including SARS-CoV and Middle East respiratory syndrome (MERS-CoV). RDV is a nucleotide analog inhibitor of RNA-dependent RNA polymerases (RdRps). Here, we co-expressed the MERS-CoV nonstructural proteins nsp5, nsp7, nsp8, and nsp12 (RdRp) in insect cells as a part a polyprotein to study the mechanism of inhibition of MERS-CoV RdRp by RDV. We initially demonstrated that nsp8 and nsp12 form an active complex. The triphosphate form of the inhibitor (RDV-TP) competes with its natural counterpart ATP. Of note, the selectivity value for RDV-TP obtained here with a steady-state approach suggests that it is more efficiently incorporated than ATP and two other nucleotide analogues. Once incorporated at position i, the inhibitor caused RNA synthesis arrest at position i+3. Hence, the likely mechanism of action is delayed RNA chain termination. The additional three nucleotides may protect the inhibitor from excision by the viral 3′-5′ exonuclease activity. Together, these results help to explain the high potency of RDV against RNA viruses in cell-based assays.

Keywords: Ebola virus (EBOV); Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2; RNA-dependent RNA polymerase (RdRp), viral replicase; coronavirus, positive-sense RNA virus; drug development; enzyme inhibitor; nucleoside/nucleotide analogue; plus-stranded RNA virus; remdesivir, antiviral drug, RNA chain-termination; viral polymerase.

Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Keywords: MERS-CoV; Coronavirus; Antivirals; Remdesivir.

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Overlapping and Discrete #Aspects of the #Pathology and #Pathogenesis of the Emerging Human Pathogenic #Coronaviruses #SARS-CoV, #MERS-CoV, and 2019-nCoV (J Med Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

 J Med Virol  2020 Feb 13 [Online ahead of print]

Overlapping and Discrete Aspects of the Pathology and Pathogenesis of the Emerging Human Pathogenic Coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV

Jia Liu 1 2, Xin Zheng 1 2, Qiaoxia Tong 1, Wei Li 1, Baoju Wang 1 2, Kathrin Sutter 3 2, Mirko Trilling 3 2, Mengji Lu 3 2, Ulf Dittmer 3 2, Dongliang Yang 1 2

Affiliations: 1 Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. 2 Joint International laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan, 430022, China. 3 Institute for Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, 45147, Germany.

PMID: 32056249 DOI: 10.1002/jmv.25709

 

Abstract

First reported from Wuhan, PR China, on 31 December 2019, the ongoing outbreak of a novel coronavirus (2019-nCoV) causes great global concerns. Based on the advice of the International Health Regulations Emergency Committee and the fact that to date 24 other countries also reported cases, the WHO Director-General declared that the outbreak of 2019-nCoV constitutes a Public Health Emergency of International Concern on 30 January 2020. Together with the other two highly pathogenic coronaviruses, the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), 2019-nCov and other yet to be identified coronaviruses pose a global threat to public health. In this mini-review, we provide a brief introduction on the pathology and pathogenesis of SARS-CoV and MERS-CoV, and extrapolate this knowledge to the newly identified 2019-nCoV.

Keywords: Coronavirus < Virus classification; Immnopathology < Immune responses; Respiratory tract < Pathogenesis.

This article is protected by copyright. All rights reserved.

Keywords: Coronavirus; SARS-CoV-2; COVID-19; MERS-CoV; Immunopathology; Viral pathogenesis.

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