From #SARS to #MERS, Thrusting #Coronaviruses into the Spotlight (Viruses, abstract)

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

Viruses. 2019 Jan 14;11(1). pii: E59. doi: 10.3390/v11010059.

From SARS to MERS, Thrusting Coronaviruses into the Spotlight.

Song Z1,2,3, Xu Y4,5,6, Bao L7,8,9, Zhang L10,11,12, Yu P13,14,15, Qu Y16,17,18, Zhu H19,20,21, Zhao W22,23,24, Han Y25,26,27, Qin C28,29,30.

Author information: 1 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing 100021, China. songzhiqi1989@foxmail.com. 2 NHC Key Laboratory of Human Disease Comparative Medicine, the Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China. songzhiqi1989@foxmail.com. 3 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China. songzhiqi1989@foxmail.com. 4 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing 100021, China. xuyanf2009@163.com. 5 NHC Key Laboratory of Human Disease Comparative Medicine, the Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China. xuyanf2009@163.com. 6 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China. xuyanf2009@163.com. 7 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing 100021, China. bllmsl@aliyun.com. 8 NHC Key Laboratory of Human Disease Comparative Medicine, the Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China. bllmsl@aliyun.com. 9 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China. bllmsl@aliyun.com. 10 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing 100021, China. zhangling@cnilas.org. 11 NHC Key Laboratory of Human Disease Comparative Medicine, the Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China. zhangling@cnilas.org. 12 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China. zhangling@cnilas.org. 13 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing 100021, China. pinyucau@gmail.com. 14 NHC Key Laboratory of Human Disease Comparative Medicine, the Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China. pinyucau@gmail.com. 15 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China. pinyucau@gmail.com. 16 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing 100021, China. quyj@cnilas.org. 17 NHC Key Laboratory of Human Disease Comparative Medicine, the Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China. quyj@cnilas.org. 18 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China. quyj@cnilas.org. 19 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing 100021, China. zhuh@cnilas.org. 20 NHC Key Laboratory of Human Disease Comparative Medicine, the Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China. zhuh@cnilas.org. 21 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China. zhuh@cnilas.org. 22 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing 100021, China. hnndwenjiezhao@163.com. 23 NHC Key Laboratory of Human Disease Comparative Medicine, the Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China. hnndwenjiezhao@163.com. 24 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China. hnndwenjiezhao@163.com. 25 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing 100021, China. 18510165683@163.com. 26 NHC Key Laboratory of Human Disease Comparative Medicine, the Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China. 18510165683@163.com. 27 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China. 18510165683@163.com. 28 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical Collage (PUMC), Beijing 100021, China. qinchuan@pumc.edu.cn. 29 NHC Key Laboratory of Human Disease Comparative Medicine, the Institute of Laboratory Animal Sciences, CAMS&PUMC, Beijing 100021, China. qinchuan@pumc.edu.cn. 30 Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing 100021, China. qinchuan@pumc.edu.cn.

 

Abstract

Coronaviruses (CoVs) have formerly been regarded as relatively harmless respiratory pathogens to humans. However, two outbreaks of severe respiratory tract infection, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), as a result of zoonotic CoVs crossing the species barrier, caused high pathogenicity and mortality rates in human populations. This brought CoVs global attention and highlighted the importance of controlling infectious pathogens at international borders. In this review, we focus on our current understanding of the epidemiology, pathogenesis, prevention, and treatment of SARS-CoV and MERS-CoV, as well as provides details on the pivotal structure and function of the spike proteins (S proteins) on the surface of each of these viruses. For building up more suitable animal models, we compare the current animal models recapitulating pathogenesis and summarize the potential role of host receptors contributing to diverse host affinity in various species. We outline the research still needed to fully elucidate the pathogenic mechanism of these viruses, to construct reproducible animal models, and ultimately develop countermeasures to conquer not only SARS-CoV and MERS-CoV, but also these emerging coronaviral diseases.

KEYWORDS: MERS-CoV; SARS-CoV; animal model; coronaviruses; prevention and treatment; spike proteins

PMID: 30646565 DOI: 10.3390/v11010059

Keywords: MERS-CoV; SARS; Coronavirus.

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TMPRSS2 contributes to #virus spread and #immunopathology in the #airways of murine models after #coronavirus infection (J Virol., abstract)

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

TMPRSS2 contributes to virus spread and immunopathology in the airways of murine models after coronavirus infection

Naoko Iwata-Yoshikawa, Tadashi Okamura, Yukiko Shimizu, Hideki Hasegawa, Makoto Takeda, Noriyo Nagata

DOI: 10.1128/JVI.01815-18

 

ABSTRACT

Transmembrane serine protease TMPRSS2 activates the spike protein of highly pathogenic human coronaviruses such as severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East respiratory syndrome-related coronavirus (MERS-CoV). In vitro, activation induces virus-cell membrane fusion at the cell surface. However, the roles of TMPRSS2 during coronavirus infection in vivo are unclear. Here, we used animal models of SARS-CoV and MERS-CoV infection to investigate the role of TMPRSS2. Th-1-prone C57BL/6 mice and TMPRSS2-knockout (KO) mice were used for SARS-CoV infection, and transgenic mice expressing the human MERS-CoV receptor, hDPP4-Tg mice, and TMPRSS2-KO hDPP4-Tg mice were used for MERS-CoV infection. After experimental infection, TMPRSS2-deficient mouse strains showed reduced body weight loss and viral kinetics in the lungs. Lack of TMPRSS2 affected the primary sites of infection and virus spread within the airway, accompanied by less severe immunopathology. However, TMPRSS2-KO mice showed weakened inflammatory chemokine and/or cytokine responses to intranasal stimulation with poly (I:C), a Toll-like receptor 3 agonist. In conclusion, TMPRSS2 plays a crucial role in viral spread within the airway of murine models infected by SARS-CoV and MERS-CoV and in the resulting immunopathology.

 

IMPORTANCE

Broad-spectrum antiviral drugs against highly pathogenic coronaviruses and other emerging viruses are desirable to enable a rapid response to pandemic threats. Transmembrane protease serine type2 (TMPRSS2), a protease belonging to the type II transmembrane serine protease family, cleaves the coronavirus spike protein, making it a potential therapeutic target for coronavirus infections. Here, we examined the role of TMPRSS2 using animal models of SARS-CoV and MERS-CoV infection. The results suggest that lack of TMPRSS2 in the airways reduces the severity of lung pathology after infection by SARS-CoV and MERS-CoV. Taken together, the results will facilitate development of novel targets for coronavirus therapy.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Coronavirus; MERS-CoV; SARS; Viral pathogenesis.

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#Replication of #MERS and #SARS #coronaviruses in #bat cells offers insights to their ancestral origins (Emerg Microbes Infect., abstract)

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

Emerg Microbes Infect. 2018 Dec 10;7(1):209. doi: 10.1038/s41426-018-0208-9.

Replication of MERS and SARS coronaviruses in bat cells offers insights to their ancestral origins.

Lau SKP1,2,3,4, Fan RYY5, Luk HKH5, Zhu L5, Fung J5, Li KSM5, Wong EYM5, Ahmed SS5, Chan JFW6,5,7,8, Kok RKH6,5,7,8, Chan KH6,5,7,8, Wernery U9, Yuen KY6,5,7,8, Woo PCY10,11,12,13.

Author information: 1 State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. skplau@hku.hk. 2 Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. skplau@hku.hk. 3 Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. skplau@hku.hk. 4 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. skplau@hku.hk. 5 Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. 6 State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. 7 Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. 8 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. 9 Central Veterinary Research Laboratory, Dubai, United Arab Emirates. 10 State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. pcywoo@hku.hk. 11 Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. pcywoo@hku.hk. 12 Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. pcywoo@hku.hk. 13 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. pcywoo@hku.hk.

 

Abstract

Previous findings of Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses in bats, and the ability of Tylonycteris-BatCoV HKU4 spike protein to utilize MERS-CoV receptor, human dipeptidyl peptidase 4 hDPP4, suggest a bat ancestral origin of MERS-CoV. We developed 12 primary bat cell lines from seven bat species, including Tylonycteris pachypus, Pipistrellus abramus and Rhinolophus sinicus (hosts of Tylonycteris-BatCoV HKU4, Pipistrellus-BatCoV HKU5, and SARS-related-CoV respectively), and tested their susceptibilities to MERS-CoVs, SARS-CoV, and human coronavirus 229E (HCoV-229E). Five cell lines, including P. abramus and R. sinicus but not T. pachypus cells, were susceptible to human MERS-CoV EMC/2012. However, three tested camel MERS-CoV strains showed different infectivities, with only two strains capable of infecting three and one cell lines respectively. SARS-CoV can only replicate in R. sinicus cells, while HCoV-229E cannot replicate in any bat cells. Bat dipeptidyl peptidase 4 (DPP4) sequences were closely related to those of human and non-human primates but distinct from dromedary DPP4 sequence. Critical residues for binding to MERS-CoV spike protein were mostly conserved in bat DPP4. DPP4 was expressed in the five bat cells susceptible to MERS-CoV, with significantly higher mRNA expression levels than those in non-susceptible cells (P = 0.0174), supporting that DPP4 expression is critical for MERS-CoV infection in bats. However, overexpression of T. pachypus DPP4 failed to confer MERS-CoV susceptibility in T. pachypus cells, suggesting other cellular factors in determining viral replication. The broad cellular tropism of MERS-CoV should prompt further exploration of host diversity of related viruses to identify its ancestral origin.

PMID: 30531999 DOI: 10.1038/s41426-018-0208-9

Keywords: Coronavirus; MERS-CoV; SARS; Bats.

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Middle East respiratory syndrome #coronavirus (#MERS-CoV): #Impact on #Saudi Arabia, 2015 (Saudi J Biol Sci., abstract)

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

Saudi J Biol Sci. 2018 Nov;25(7):1402-1405. doi: 10.1016/j.sjbs.2016.09.020. Epub 2016 Oct 1.

Middle East respiratory syndrome coronavirus (MERS-CoV): Impact on Saudi Arabia, 2015.

Faridi U1.

Author information: 1 Department of Biochemistry, Tabuk University, Tabuk, Saudi Arabia.

 

Abstract

Middle East respiratory syndrome is the acute respiratory syndrome caused by betacoronavirus MERS-CoV. The first case of this disease was reported from Saudi Arabia in 2012. This virus is lethal and is a close relative of a severe acute respiratory syndrome (SARS), which is responsible for more than 3000 deaths in 2002-2003. According to Ministry of Health, Saudi Arabia. The number of new cases is 457 in 2015. Riyadh has the highest number of reports in comparison to the other cities. According to this report, males are more susceptible than female, especially after the age of 40. Because of the awareness and early diagnosis the incidence is falling gradually. The pre-existence of another disease like cancer or diabetic etc. boosts the infection. MERS is a zoonotic disease and human to human transmission is low. The MERS-CoV is a RNA virus with protein envelope. On the outer surface, virus has spike like glycoprotein which is responsible for the attachment and entrance inside host cells. There is no specific treatment for the MERS-CoV till now, but drugs are in pipeline which bind with the spike glycoprotein and inhibit its entrance host cells. MERS-CoV and SAR-CoV are from the same genus, so it was thought that the drugs which inhibit the growth of SARS-CoV can also inhibit the growth of MERS-CoV but those drugs are not completely inhibiting virus activity. Until we don’t have proper structure and the treatment of MERS-CoV, We should take precautions, especially the health care workers, Camel owners and Pilgrims during Hajj and Umrah, because they are at a higher risk of getting infected.

KEYWORDS: Betacoronavirus; MERS-CoV; SARS; Saudi Arabia

PMID: 30505188 PMCID: PMC6252006  DOI: 10.1016/j.sjbs.2016.09.020

Keywords: Coronavirus; Betacoronavirus; MERS-CoV; SARS; Saudi Arabia; Human; Camels.

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Molecular #identification of #Betacoronavirus in #bats from #Sardinia (#Italy): first detection and phylogeny (Virus Genes., abstract)

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

Virus Genes. 2018 Nov 13. doi: 10.1007/s11262-018-1614-8. [Epub ahead of print]

Molecular identification of Betacoronavirus in bats from Sardinia (Italy): first detection and phylogeny.

Lecis R1,2, Mucedda M3, Pidinchedda E3, Pittau M4,5, Alberti A4,5.

Author information: 1 Department of Veterinary Medicine, University of Sassari, Via Vienna 2, 07100, Sassari, Italy. rlecis@uniss.it. 2 Mediterranean Centre for Disease Control, University of Sassari, Via Vienna 2, 07100, Sassari, Italy. rlecis@uniss.it. 3 Centro Pipistrelli Sardegna, Via G. Leopardi 1, 07100, Sassari, Italy. 4 Department of Veterinary Medicine, University of Sassari, Via Vienna 2, 07100, Sassari, Italy. 5 Mediterranean Centre for Disease Control, University of Sassari, Via Vienna 2, 07100, Sassari, Italy.

 

Abstract

Bats may be natural reservoirs for a large variety of emerging viruses, including mammalian coronaviruses (CoV). The recent emergence of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) in humans, with evidence that these viruses may have their ancestry in bats, highlights the importance of virus surveillance in bat populations. Here, we report the identification and molecular characterization of a bat β-Coronavirus, detected during a viral survey carried out on different bat species in the island of Sardinia (Italy). Cutaneous, oral swabs, and faecal samples were collected from 46 bats, belonging to 15 different species, and tested for viral presence. Coronavirus RNA was detected in faecal samples from three different species: the greater horseshoe bat (Rhinolophus ferrumequinum), the brown long-eared bat (Plecotus auritus), and the European free-tailed bat (Tadarida teniotis). Phylogenetic analyses based on RNA-dependent RNA polymerase (RdRp) sequences assigned the detected CoV to clade 2b within betacoronaviruses, clustering with SARS-like bat CoVs previously reported. These findings point to the need for continued surveillance of bat CoV circulating in Sardinian bats, and extend the current knowledge on CoV ecology with novel sequences detected in bat species not previously described as β-Coronavirus hosts.

KEYWORDS: Bats; Coronavirus; RNA-dependent RNA polymerase; Rhinolophus ferrumequinum; Sardinia

PMID: 30426315 DOI: 10.1007/s11262-018-1614-8

Keywords: Coronavirus; Betacoronavirus; SARS; Bats; Italy.

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#AIDS, #Avian #flu, #SARS, #MERS, #Ebola, #Zika… what next? (Vaccine, abstract)

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

Vaccine. 2017 Aug 16;35(35 Pt A):4470-4474. doi: 10.1016/j.vaccine.2017.04.082. Epub 2017 Jun 19.

AIDS, Avian flu, SARS, MERS, Ebola, Zika… what next?

Reperant LA1, Osterhaus ADME2.

Author information: 1 Artemis One Health Research Foundation, Utrecht, The Netherlands. 2 Artemis One Health Research Foundation, Utrecht, The Netherlands; Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine, Hannover, Germany. Electronic address: Albert.Osterhaus@tiho-hannover.de.

 

Abstract

Emerging infections have threatened humanity since times immemorial. The dramatic anthropogenic, behavioral and social changes that have affected humanity and the environment in the past century have accelerated the intrusion of novel pathogens into the global human population, sometimes with devastating consequences. The AIDS and influenza pandemics have claimed and will continue to claim millions of lives. The recent SARS and Ebola epidemics have threatened populations across borders. The emergence of MERS may well be warning signals of a nascent pandemic threat, while the potential for geographical spread of vector-borne diseases, such as Zika, but also Dengue and Chikungunya is unprecedented. Novel technologies and innovative approaches have multiplied to address and improve response preparedness towards the increasing yet unpredictable threat posed by emerging pathogens.

KEYWORDS: Emerging; Epidemics; Preparedness; Virus

PMID: 28633891 DOI: 10.1016/j.vaccine.2017.04.082 [Indexed for MEDLINE]

Keywords: Infectious Diseases; Emerging Diseases; Pandemic Preparedness; Zika Virus; Ebola; MERS-CoV; SARS; HIV/AIDS; Avian Influenza.

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Combination #attenuation offers #strategy for live-attenuated #coronavirus #vaccines (J Virol., abstract)

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

Combination attenuation offers strategy for live-attenuated coronavirus vaccines

Vineet D. Menachery1,2, Lisa E. Gralinski2, Hugh D. Mitchell4, Kenneth H. Dinnon III2, Sarah R. Leist2, Boyd L. Yount Jr.2, Eileen T. McAnarney1,2, Rachel L. Graham2, Katrina M. Waters4 and Ralph S. Baric2,3⇑

Author Affiliations: 1 Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; 2 Departments of Epidemiology and 3Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 4 Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA

 

ABSTRACT

With an ongoing threat posed by circulating zoonotic strains, new strategies are required to prepare for the next emergent coronavirus (CoV). Previously, groups had targeted conserved coronavirus proteins as a strategy to generate live-attenuated vaccine strains against current and future CoVs. With this in mind, we explored whether manipulation of CoV NSP16, a conserved 2′O methyltransferase (MTase), could provide a broad attenuation platform against future emergent strains. Using the SARS-CoV mouse model, a NSP16 mutant vaccine was evaluated for protection from heterologous challenge, efficacy in the aging host, and potential for reversion to pathogenesis. Despite some success, concerns for virulence in the aged and potential for reversion makes targeting NSP16 alone an untenable approach. However, combining a 2′O MTase mutation with a previously described CoV fidelity mutant produced a vaccine strain capable of protection from heterologous virus challenge, efficacy in aged mice, and no evidence for reversion. Together, the results indicate that targeting the CoV 2′O MTase in parallel with other conserved attenuating mutations may provide a platform strategy for rapidly generating live-attenuated coronavirus vaccines.

 

Significance

Emergent coronaviruses remain a significant threat to global public health and rapid response vaccine platforms are needed to stem future outbreaks. However, failure of many previous CoV vaccine formulations has clearly highlighted the need to test efficacy under different conditions and especially in vulnerable populations like the aged and immune-compromised. This study illustrates that despite success in young models, the 2′O methyltransferase mutant carries too much risk for pathogenesis and reversion in vulnerable models to be used as a stand-alone vaccine strategy. Importantly, the 2′O methyltransferase mutation can be paired with other attenuating approaches to provide robust protection from heterologous challenge and in vulnerable populations. Coupled with increased safety and reduced pathogenesis, the study highlights the potential for 2′O methyltransferase attenuation as a major component of future live-attenuated coronavirus vaccines.

 

FOOTNOTES

Corresponding Author: Ralph S. Baric, Address: University of North Carolina at Chapel Hill, 2107 McGavran-Greenberg Hall CB 7435, Chapel Hill, NC 27599-7435, Telephone:
919-966-7991 Fax: 919-966-0584, Email: Rbaric@email.unc.edu

Copyright © 2018 American Society for Microbiology. All Rights Reserved.

Keywords: Coronavirus; SARS; Vaccines; Animal Models.

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