Small Particle #Aerosol #Exposure of African Green #Monkeys to #MERS-CoV as a #Model for Highly Pathogenic #Coronavirus Infection (Emerg Infect Dis., abstract)

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

Volume 26, Number 12—December 2020 | Research

Small Particle Aerosol Exposure of African Green Monkeys to MERS-CoV as a Model for Highly Pathogenic Coronavirus Infection

Allison Totura1, Virginia Livingston, Ondraya Frick, David Dyer, Donald Nichols, and Aysegul Nalca

Author affiliations: Author affiliation: US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA

 

Abstract

Emerging coronaviruses are a global public health threat because of the potential for person-to-person transmission and high mortality rates. Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing lethal respiratory disease in »35% of cases. Primate models of coronavirus disease are needed to support development of therapeutics, but few models exist that recapitulate severe disease. For initial development of a MERS-CoV primate model, 12 African green monkeys were exposed to 103, 104, or 105 PFU target doses of aerosolized MERS-CoV. We observed a dose-dependent increase of respiratory disease signs, although all 12 monkeys survived for the 28-day duration of the study. This study describes dose-dependent effects of MERS-CoV infection of primates and uses a route of infection with potential relevance to MERS-CoV transmission. Aerosol exposure of African green monkeys might provide a platform approach for the development of primate models of novel coronavirus diseases.

Keywords: MERS-CoV-2; Coronavirus; Animal models.

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#Modelling the #inactivation of #viruses from the #Coronaviridae family in response to #temperature and relative #humidity in #suspensions or #surfaces (Appl Environ Microbiol., abstract)

[Source: Applied and Environmental Microbiology, full page: (LINK). Abstract, edited.]

Modelling the inactivation of viruses from the Coronaviridae family in response to temperature and relative humidity in suspensions or surfaces.

Laurent Guillier, Sandra Martin-Latil, Estelle Chaix, Anne Thébault, Nicole Pavio, Sophie Le Poder; on behalf of Covid-19 Emergency Collective Expert Appraisal Group, Christophe Batéjat, Fabrice Biot, Lionel Koch, Don Schaffner, Moez Sanaa

DOI: 10.1128/AEM.01244-20

 

ABSTRACT

Temperature and relative humidity are major factors determining virus inactivation in the environment. This article reviews inactivation data of coronaviruses on surfaces and in liquids from published studies and develops secondary models to predict coronaviruses inactivation as a function of temperature and relative humidity. A total of 102 D-values (time to obtain a log10 reduction of virus infectivity), including values for SARS-CoV-2, were collected from 26 published studies. The values obtained from the different coronaviruses and studies were found to be generally consistent. Five different models were fitted to the global dataset of D-values. The most appropriate model considered temperature and relative humidity. A spreadsheet predicting the inactivation of coronaviruses and the associated uncertainty is presented and can be used to predict virus inactivation for untested temperatures, time points or any coronavirus strains belonging to Alphacoronavirus and Betacoronavirus genera.

 

Importance:

The prediction of the persistence of SARS-CoV-2 on fomites is essential to investigate the importance of contact transmission. This study collects available information on inactivation kinetics of coronaviruses in both solid and liquid fomites and creates a mathematical model for the impact of temperature and relative humidity on virus persistence. The predictions of the model can support more robust decision-making and could be useful in various public health contexts. Having a calculator for the natural clearance of SARS-CoV-2 depending on temperature and relative humidity could be a valuable operational tool for public authorities.

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

Keywords: SARS-CoV-2; COVID-19; Coronavirus; Betacoronavirus.

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#Assessment of #Th1/Th2 #cytokines among patients with #MERS #coronavirus infection (Int Immunol., abstract)

[Source: International Immunology, full page: (LINK). Abstract, edited.]

Assessment of Th1/Th2 cytokines among patients with Middle East respiratory syndrome coronavirus infection

Abdulkarim Alhetheel, Ahmed Albarrag, Zahid Shakoor, Ali Somily, Mazin Barry, Hifa Altalhi, Muhammed Bakhrebah, Majed Nassar, Mohamed B Alfageeh, Ayed Assiri, Sarah H Alfaraj, Ziad A Memish

International Immunology, dxaa047, https://doi.org/10.1093/intimm/dxaa047

Published: 10 July 2020

 

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a member of the beta-coronavirus genus of zoonotic origin that emerged in the Arabian Peninsula and is associated with significant morbidity and mortality. This study was conducted to assess the plasma levels of cytokines to evaluate the Th1/Th2 status among 46 MERS-CoV infected patients (19 asymptomatic and 27 symptomatic) and 52 normal healthy controls using a customized luminex kit. Comparative analysis of data between MERS-CoV infected patients and normal healthy controls revealed that whereas no difference was observed between asymptomatic MERS-CoV patients and controls, the mean plasma levels of IL-10 (44.69 ± 40.04 pg/mL vs 14.84 ± 6.96 pg/mL; p<0.0001), IL-4 (22.46 ± 8.02 pg/mL vs 16.01 ± 9.97 pg/mL; p<0.0001), IL-5 (10.78 ± 2.86 pg/mL vs 8.06 ± 1.41 pg/mL; p<0.0001) and IL-13 (14.51 ± 3.97 pg/mL vs 11.53 ± 4.16 pg/mL; p<0.003) in MERS-CoV symptomatic patients were significantly higher than the normal controls. The mean plasma levels of IFN-γ and IL-12 were no different among the study groups. The cytokine profile among symptomatic MERS-CoV infected patients was skewed to Th2 type immune response.

Th1/Th2 cytokines, MERS-CoV, Saudi Arabia

Issue Section: Short Communication

This content is only available as a PDF.

© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Society for Immunology.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Keywords: MERS-CoV; Cytokines; Immunopathology.

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A #universal #design of #betacoronavirus #vaccines against #COVID19, #MERS and #SARS (Cell, abstract)

[Source: Cell, full page: (LINK). Abstract, edited.]

A universal design of betacoronavirus vaccines against COVID-19, MERS and SARS

Lianpan Dai,  Tianyi Zheng, Kun Xu, Yuxuan Han, Lili Xu, Enqi Huang, Yaling An, Yingjie Cheng, Shihua Li, Mei Liu, Mi Yang, Yan Li, Huijun Cheng, Yuan Yuan, Wei Zhang, Changwen Ke, Gary Wong, Jianxun Qi, Chuan Qin, Jinghua Yan, George F. Gao

Published: June 28, 2020 | DOI: https://doi.org/10.1016/j.cell.2020.06.035

 

Highlights

  • A dimeric form of MERS-CoV RBD is highly immunogenic and protective in mice
  • RBD-dimer structure guides further design of a homogeneous dimer by tandem repeat
  • The strategy is generalizable to design beta-CoV vaccines against COVID-19 and SARS
  • CoV RBD-dimer immunogens can be produced at high yields in pilot scale production

 

Summary

Vaccines are urgently needed to control the ongoing pandemic COVID-19 and previously-emerging MERS/SARS caused by coronavirus (CoV) infections. The CoV spike receptor-binding domain (RBD) is an attractive vaccine target but is undermined by limited immunogenicity. We describe a dimeric form of MERS-CoV RBD that overcomes this limitation. The RBD-dimer significantly increased neutralizing antibody (NAb) titers compared to conventional monomeric form and protected mice against MERS-CoV infection. Crystal structure showed RBD-dimer fully exposed dual receptor-binding motifs, the major target for NAbs. Structure-guided design further yielded a stable version of RBD-dimer as a tandem repeat single-chain (RBD-sc-dimer) which retained the vaccine potency. We generalized this strategy to design vaccines against COVID-19 and SARS, achieving 10-100-fold enhancement of NAb titers. RBD-sc-dimers in pilot scale production yielded high yields, supporting their scalability for further clinical development. The framework of immunogen design can be universally applied to other beta-CoV vaccines to counter emerging threats.

Accepted: June 23, 2020 – Received in revised form: June 3, 2020 – Received: May 4, 2020

Publication stage In Press Accepted Manuscript

Identification DOI: https://doi.org/10.1016/j.cell.2020.06.035

Copyright © 2020 Elsevier Inc.

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

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Novel #Immunoglobulin #Domain #Proteins Provide Insights into #Evolution and #Pathogenesis of #SARS-CoV-2-Related Viruses (mBio, abstract)

[Source: mBio, full page: (LINK). Abstract, edited.]

Novel Immunoglobulin Domain Proteins Provide Insights into Evolution and Pathogenesis of SARS-CoV-2-Related Viruses

Yongjun Tan, Theresa Schneider, Matthew Leong, L. Aravind, Dapeng Zhang

Igor B. Zhulin, Editor

DOI: 10.1128/mBio.00760-20

 

ABSTRACT

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was recently identified as the causative agent for the coronavirus disease 2019 (COVID-19) outbreak that has generated a global health crisis. We use a combination of genomic analysis and sensitive profile-based sequence and structure analysis to understand the potential pathogenesis determinants of this virus. As a result, we identify several fast-evolving genomic regions that might be at the interface of virus-host interactions, corresponding to the receptor binding domain of the Spike protein, the three tandem Macro fold domains in ORF1a, and the uncharacterized protein ORF8. Further, we show that ORF8 and several other proteins from alpha- and beta-CoVs belong to novel families of immunoglobulin (Ig) proteins. Among them, ORF8 is distinguished by being rapidly evolving, possessing a unique insert, and having a hypervariable position among SARS-CoV-2 genomes in its predicted ligand-binding groove. We also uncover numerous Ig domain proteins from several unrelated metazoan viruses, which are distinct in sequence and structure but share comparable architectures to those of the CoV Ig domain proteins. Hence, we propose that SARS-CoV-2 ORF8 and other previously unidentified CoV Ig domain proteins fall under the umbrella of a widespread strategy of deployment of Ig domain proteins in animal viruses as pathogenicity factors that modulate host immunity. The rapid evolution of the ORF8 Ig domain proteins points to a potential evolutionary arms race between viruses and hosts, likely arising from immune pressure, and suggests a role in transmission between distinct host species.

 

IMPORTANCE

The ongoing COVID-19 pandemic strongly emphasizes the need for a more complete understanding of the biology and pathogenesis of its causative agent SARS-CoV-2. Despite intense scrutiny, several proteins encoded by the genomes of SARS-CoV-2 and other SARS-like coronaviruses remain enigmatic. Moreover, the high infectivity and severity of SARS-CoV-2 in certain individuals make wet-lab studies currently challenging. In this study, we used a series of computational strategies to identify several fast-evolving regions of SARS-CoV-2 proteins which are potentially under host immune pressure. Most notably, the hitherto-uncharacterized protein encoded by ORF8 is one of them. Using sensitive sequence and structural analysis methods, we show that ORF8 and several other proteins from alpha- and beta-coronavirus comprise novel families of immunoglobulin domain proteins, which might function as potential immune modulators to delay or attenuate the host immune response against the viruses.

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

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Are we now observing an increasing number of #coinfections between #SARS‐CoV‐2 and other respiratory #pathogens? (J Med Virol., abstract)

[Source: Journal of Medical Virology, full page: (LINK). Abstract, edited.]

Are we now observing an increasing number of coinfections between SARS‐CoV‐2 and other respiratory pathogens?

Jorge A. Sánchez‐Duque,  Juan Pablo Orozco‐Hernández,  Daniel S. Marín‐Medina, Aleksandar Cvetkovic‐Vega,  Telmo Raul Aveiro‐Róbalo,  Alvaro Mondragon‐Cardona, …

First published: 29 May 2020 | DOI:  https://doi.org/10.1002/jmv.26089

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jmv.26089

 

Abstract

We have recently read the article by Chaung et al.,1 describing a case of SARS‐CoV‐2 and HCoV‐HKU1 coinfection. The HCoV‐HKU1 is also a member of the Betacoronavirus.

This article is protected by copyright. All rights reserved.

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

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#Proteolytic #cleavage of the #SARS-CoV-2 #spike protein and the role of the novel S1/S2 site (iScience, abstract)

[Source: iScience, full page: (LINK). Abstract, edited.]

Proteolytic cleavage of the SARS-CoV-2 spike protein and the role of the novel S1/S2 site

Javier A. Jaimes, Jean K. Millet, Gary R. Whittaker

Open Access | Published: May 28, 2020 | DOI: https://doi.org/10.1016/j.isci.2020.101212

 

Highlights

  • SARS-CoV-2 spike protein harbors a distinct 4 amino acid insertion at the S1/S2 site
  • The S1/S2 site can be cleaved by furin-like, trypsin-like and cathepsin proteases
  • The S1/S2 insert likely enhances spike protein cleavage by several proteases in vivo

 

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19) has rapidly spread to the entire world within a few months. The origin of SARS-CoV-2 has been related to the lineage  B Betacoronavirus  SARS-CoV and SARS-related coronaviruses found in bats. Early characterizations of the  SARS-CoV-2 genome revealed the existence of a distinct 4 amino acid insert within the  spike (S) protein (underlined, SPRRAR↓S), at the S1/S2 site located at the interface  between the S1 receptor binding subunit and the S2 fusion subunit. Notably, this insert  appears to be a distinguishing feature among SARS-related sequences and introduces a  potential cleavage site for the protease furin. Here, we investigate the potential role of  this novel S1/S2 cleavage site and present direct biochemical evidence for proteolytic  processing by a variety of proteases. We discuss these findings in the context of the  origin of SARS-CoV-2, viral stability and transmission.

Accepted: May 27, 2020 – Received in revised form: May 4, 2020 – Received: April 10, 2020

Publication stage In Press Accepted Manuscript

Identification DOI: https://doi.org/10.1016/j.isci.2020.101212

Copyright © 2020

Keywords: SARS-CoV-2; COVID-19.

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Are #pangolins the intermediate #host of the 2019 novel #coronavirus (#SARS-CoV-2)? (PLOS Pathog., abstract)

[Source: PLOS Pathogens, full page: (LINK). Abstract, edited.]

OPEN ACCESS |  PEER-REVIEWED | RESEARCH ARTICLE

Are pangolins the intermediate host of the 2019 novel coronavirus (SARS-CoV-2)?

Ping Liu , Jing-Zhe Jiang , Xiu-Feng Wan, Yan Hua, Linmiao Li, Jiabin Zhou, Xiaohu Wang, Fanghui Hou, Jing Chen, Jiejian Zou, Jinping Chen

Published: May 14, 2020 | DOI: https://doi.org/10.1371/journal.ppat.1008421

 

Abstract

The outbreak of a novel corona Virus Disease 2019 (COVID-19) in the city of Wuhan, China has resulted in more than 1.7 million laboratory confirmed cases all over the world. Recent studies showed that SARS-CoV-2 was likely originated from bats, but its intermediate hosts are still largely unknown. In this study, we assembled the complete genome of a coronavirus identified in 3 sick Malayan pangolins. The molecular and phylogenetic analyses showed that this pangolin coronavirus (pangolin-CoV-2020) is genetically related to the SARS-CoV-2 as well as a group of bat coronaviruses but do not support the SARS-CoV-2 emerged directly from the pangolin-CoV-2020. Our study suggests that pangolins are natural hosts of Betacoronaviruses. Large surveillance of coronaviruses in pangolins could improve our understanding of the spectrum of coronaviruses in pangolins. In addition to conservation of wildlife, minimizing the exposures of humans to wildlife will be important to reduce the spillover risks of coronaviruses from wild animals to humans.

 

Author summary

Recently, a novel coronavirus, SARS-CoV-2, caused a still ongoing pandemic. Epidemiological study suggested this virus was associated with a wet market in Wuhan, China. However, the exact source of this virus is still unknown. In this study, we attempted to assemble the complete genome of a coronavirus identified from two groups of sick Malayan pangolins, which were likely to be smuggled for black market trade. The molecular and evolutionary analyses showed that this pangolin coronavirus we assembled was genetically associated with the SARS-CoV-2 but was not likely its precursor. This study suggested that pangolins are natural hosts of coronaviruses. Determining the spectrum of coronaviruses in pangolins can help understand the natural history of coronaviruses in wildlife and at the animal-human interface, and facilitate the prevention and control of coronavirus-associated emerging diseases.

___

Citation: Liu P, Jiang J-Z, Wan X-F, Hua Y, Li L, Zhou J, et al. (2020) Are pangolins the intermediate host of the 2019 novel coronavirus (SARS-CoV-2)? PLoS Pathog 16(5): e1008421. https://doi.org/10.1371/journal.ppat.1008421

Editor: Stanley Perlman, University of Iowa, UNITED STATES

Received: February 14, 2020; Accepted: April 8, 2020; Published: May 14, 2020

Copyright: © 2020 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All our files are available from the GeneBank database (accession number 2312773).

Funding: This project was supported by wildlife disease monitoring and early warning system maintenance project from National Forestry and Grassland Administration (2019072) to Chen JP, GDAS Special Project of Science and Technology Development (grant number 2020GDASYL-20200103090, 2018GDASCX-0107) to Liu P.,Guangzhou Science Technology and Innovation Commission (grant number 201804020080) to Chen JP, Natural Science Foundation of China (grant number 31972847) to Jiang JZ, Guangzhou science and technology project (grant number 2019001) to Chen JP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: No authors have competing interests.

Keywords: SARS-CoV-2; Betacoronavirus; Pangolins; Wildlife.

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Multivariate #analyses of #codon usage of #SARS-CoV-2 and other #betacoronaviruses (Virus Evol., abstract)

[Source: Virus Evolution, full page: (LINK). Abstract, edited.]

Multivariate analyses of codon usage of SARS-CoV-2 and other betacoronaviruses

Haogao Gu, Daniel K W Chu, Malik Peiris, Leo L M Poon

Virus Evolution, Volume 6, Issue 1, January 2020,  veaa032, https://doi.org/10.1093/ve/veaa032

Published: 14 May 2020

 

Abstract

Coronavirus disease 2019 (COVID-19) is a global health concern as it continues to spread within China and beyond. The causative agent of this disease, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belongs to the genus Betacoronavirus, which also includes severe acute respiratory syndrome-related coronavirus (SARSr-CoV) and Middle East respiratory syndrome-related coronavirus (MERSr-CoV). Codon usage of viral genes are believed to be subjected to different selection pressures in different host environments. Previous studies on codon usage of influenza A viruses helped identify viral host origins and evolution trends, however, similar studies on coronaviruses are lacking. In this study, we compared the codon usage bias using global correspondence analysis (CA), within-group CA and between-group CA. We found that the bat RaTG13 virus best matched the overall codon usage pattern of SARS-CoV-2 in orf1ab, spike and nucleocapsid genes, while the pangolin P1E virus had a more similar codon usage in membrane gene. The amino acid usage pattern of SARS-CoV-2 was generally found similar to bat and human SARSr-CoVs. However, we found greater synonymous codon usage differences between SARS-CoV-2 and its phylogenetic relatives on spike and membrane genes, suggesting these two genes of SARS-CoV-2 are subjected to different evolutionary pressures.

SARS-CoV-2, coronavirus, codon usage analysis, WCA

Issue Section:  RAPID COMMUNICATION

Keywords: SARS-CoV-2; COVID-19; Bats; Pangolins; Betacoronavirus.

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A novel #bat #coronavirus closely related to #SARS-CoV-2 contains natural insertions at the #S1/S2 cleavage site of the #spike protein (Cell Curr Biol., abstract)

[Source: Cell Current Biology, full page: (LINK). Abstract, edited.]

A novel bat coronavirus closely related to SARS-CoV-2 contains natural insertions at the S1/S2 cleavage site of the spike protein

Hong Zhou 8, Xing Chen 8, Tao Hu 8, Juan Li 8, Hao Song, Yanran Liu, Peihan Wang, Di Liu, Jing Yang, Edward C. Holmes, Alice C. Hughes, Yuhai Bi, Weifeng Shi 9

Published: May 10, 2020 | DOI: https://doi.org/10.1016/j.cub.2020.05.023

 

Summary

The unprecedented pandemic of pneumonia caused by a novel coronavirus, SARS-CoV-2, in China and beyond has had major public health impacts on a global scale [1,2]. Although bats are regarded as the most likely natural hosts for SARS-CoV-2 [3], the origins of the virus remain unclear. Here, we report a novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomics analysis of samples from 227 bats collected from Yunnan Province in China between May and October, 2019. Notably, RmYN02 shares 93.3% nucleotide identity with SARS-CoV-2 at the scale of the complete virus genome and 97.2% identity in the 1ab gene, in which it is the closest relative of SARS-CoV-2 reported to date. In contrast, RmYN02 showed low sequence identity (61.3%) to SARS-CoV-2 in the receptor binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2). Critically, and in a similar manner to SARS-CoV-2, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the spike (S) protein. This provides strong evidence that such insertion events can occur naturally in animal betacoronaviruses.

Accepted: May 6, 2020 – Received in revised form: May 1, 2020 – Received: April 16, 2020

Publication stage In Press Accepted Manuscript

Identification DOI: https://doi.org/10.1016/j.cub.2020.05.023

Copyright © 2020 Elsevier Inc.

Keywords: Betacoronavirus; Bats; Wildlife; SARS-CoV-2.

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