Viruses

Editorial

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6 pages, 166 KiB

Open AccessEditorial

MERS Coronavirus: An Emerging Zoonotic Virus

by Fang Li and Lanying Du

Viruses 2019, 11(7), 663; https://doi.org/10.3390/v11070663 - 19 Jul 2019

Cited by 22 | Viewed by 7484

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging virus that was first reported in humans in June 2012 [...] Full article

(This article belongs to the Special Issue MERS-CoV)

Research

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13 pages, 3356 KiB

Open AccessArticle

Lack of Middle East Respiratory Syndrome Coronavirus Transmission in Rabbits

by W. Widagdo, Nisreen M. A. Okba, Mathilde Richard, Dennis de Meulder, Theo M. Bestebroer, Pascal Lexmond, Elmoubasher A. B. A. Farag, Mohammed Al-Hajri, Koert J. Stittelaar, Leon de Waal, Geert van Amerongen, Judith M. A. van den Brand, Bart L. Haagmans and Sander Herfst

Viruses 2019, 11(4), 381; https://doi.org/10.3390/v11040381 - 24 Apr 2019

Cited by 10 | Viewed by 5799

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) transmission from dromedaries to humans has resulted in major outbreaks in the Middle East. Although some other livestock animal species have been shown to be susceptible to MERS-CoV, it is not fully understood why the spread of [...] Read more.

Middle East respiratory syndrome coronavirus (MERS-CoV) transmission from dromedaries to humans has resulted in major outbreaks in the Middle East. Although some other livestock animal species have been shown to be susceptible to MERS-CoV, it is not fully understood why the spread of the virus in these animal species has not been observed in the field. In this study, we used rabbits to further characterize the transmission potential of MERS-CoV. In line with the presence of MERS-CoV receptor in the rabbit nasal epithelium, high levels of viral RNA were shed from the nose following virus inoculation. However, unlike MERS-CoV-infected dromedaries, these rabbits did not develop clinical manifestations including nasal discharge and did shed only limited amounts of infectious virus from the nose. Consistently, no transmission by contact or airborne routes was observed in rabbits. Our data indicate that despite relatively high viral RNA levels produced, low levels of infectious virus are excreted in the upper respiratory tract of rabbits as compared to dromedary camels, thus resulting in a lack of viral transmission. Full article

(This article belongs to the Special Issue MERS-CoV)

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13 pages, 4852 KiB

Open AccessArticle

Efficacy of an Adjuvanted Middle East Respiratory Syndrome Coronavirus Spike Protein Vaccine in Dromedary Camels and Alpacas

by Danielle R. Adney, Lingshu Wang, Neeltje van Doremalen, Wei Shi, Yi Zhang, Wing-Pui Kong, Megan R. Miller, Trenton Bushmaker, Dana Scott, Emmie de Wit, Kayvon Modjarrad, Nikolai Petrovsky, Barney S. Graham, Richard A. Bowen and Vincent J. Munster

Viruses 2019, 11(3), 212; https://doi.org/10.3390/v11030212 - 2 Mar 2019

Cited by 74 | Viewed by 9259

Abstract

MERS-CoV is present in dromedary camels throughout the Middle East and Africa. Dromedary camels are the primary zoonotic reservoir for human infections. Interruption of the zoonotic transmission chain from camels to humans, therefore, may be an effective strategy to control the ongoing MERS-CoV [...] Read more.

MERS-CoV is present in dromedary camels throughout the Middle East and Africa. Dromedary camels are the primary zoonotic reservoir for human infections. Interruption of the zoonotic transmission chain from camels to humans, therefore, may be an effective strategy to control the ongoing MERS-CoV outbreak. Here we show that vaccination with an adjuvanted MERS-CoV Spike protein subunit vaccine confers complete protection from MERS-CoV disease in alpaca and results in reduced and delayed viral shedding in the upper airways of dromedary camels. Protection in alpaca correlates with high serum neutralizing antibody titers. Lower titers of serum neutralizing antibodies correlate with delayed and significantly reduced shedding in the nasal turbinates of dromedary camels. Together, these data indicate that induction of robust neutralizing humoral immune responses by vaccination of naïve animals reduces shedding that potentially could diminish the risk of zoonotic transmission. Full article

(This article belongs to the Special Issue MERS-CoV)

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14 pages, 2237 KiB

Open AccessArticle

Enhanced Ability of Oligomeric Nanobodies Targeting MERS Coronavirus Receptor-Binding Domain

by Lei He, Wanbo Tai, Jiangfan Li, Yuehong Chen, Yaning Gao, Junfeng Li, Shihui Sun, Yusen Zhou, Lanying Du and Guangyu Zhao

Viruses 2019, 11(2), 166; https://doi.org/10.3390/v11020166 - 19 Feb 2019

Cited by 29 | Viewed by 7017

Abstract

Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV), an infectious coronavirus first reported in 2012, has a mortality rate greater than 35%. Therapeutic antibodies are key tools for preventing and treating MERS-CoV infection, but to date no such agents have been approved for treatment [...] Read more.

Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV), an infectious coronavirus first reported in 2012, has a mortality rate greater than 35%. Therapeutic antibodies are key tools for preventing and treating MERS-CoV infection, but to date no such agents have been approved for treatment of this virus. Nanobodies (Nbs) are camelid heavy chain variable domains with properties distinct from those of conventional antibodies and antibody fragments. We generated two oligomeric Nbs by linking two or three monomeric Nbs (Mono-Nbs) targeting the MERS-CoV receptor-binding domain (RBD), and compared their RBD-binding affinity, RBD–receptor binding inhibition, stability, and neutralizing and cross-neutralizing activity against MERS-CoV. Relative to Mono-Nb, dimeric Nb (Di-Nb) and trimeric Nb (Tri-Nb) had significantly greater ability to bind MERS-CoV RBD proteins with or without mutations in the RBD, thereby potently blocking RBD–MERS-CoV receptor binding. The engineered oligomeric Nbs were very stable under extreme conditions, including low or high pH, protease (pepsin), chaotropic denaturant (urea), and high temperature. Importantly, Di-Nb and Tri-Nb exerted significantly elevated broad-spectrum neutralizing activity against at least 19 human and camel MERS-CoV strains isolated in different countries and years. Overall, the engineered Nbs could be developed into effective therapeutic agents for prevention and treatment of MERS-CoV infection. Full article

(This article belongs to the Special Issue MERS-CoV)

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16 pages, 3506 KiB

Open AccessArticle

Characterization of the Lipidomic Profile of Human Coronavirus-Infected Cells: Implications for Lipid Metabolism Remodeling upon Coronavirus Replication

by Bingpeng Yan, Hin Chu, Dong Yang, Kong-Hung Sze, Pok-Man Lai, Shuofeng Yuan, Huiping Shuai, Yixin Wang, Richard Yi-Tsun Kao, Jasper Fuk-Woo Chan and Kwok-Yung Yuen

Viruses 2019, 11(1), 73; https://doi.org/10.3390/v11010073 - 16 Jan 2019

Cited by 213 | Viewed by 19392

Abstract

Lipids play numerous indispensable cellular functions and are involved in multiple steps in the replication cycle of viruses. Infections by human-pathogenic coronaviruses result in diverse clinical outcomes, ranging from self-limiting flu-like symptoms to severe pneumonia with extrapulmonary manifestations. Understanding how cellular lipids may [...] Read more.

Lipids play numerous indispensable cellular functions and are involved in multiple steps in the replication cycle of viruses. Infections by human-pathogenic coronaviruses result in diverse clinical outcomes, ranging from self-limiting flu-like symptoms to severe pneumonia with extrapulmonary manifestations. Understanding how cellular lipids may modulate the pathogenicity of human-pathogenic coronaviruses remains poor. To this end, we utilized the human coronavirus 229E (HCoV-229E) as a model coronavirus to comprehensively characterize the host cell lipid response upon coronavirus infection with an ultra-high performance liquid chromatography-mass spectrometry (UPLC–MS)-based lipidomics approach. Our results revealed that glycerophospholipids and fatty acids (FAs) were significantly elevated in the HCoV-229E-infected cells and the linoleic acid (LA) to arachidonic acid (AA) metabolism axis was markedly perturbed upon HCoV-229E infection. Interestingly, exogenous supplement of LA or AA in HCoV-229E-infected cells significantly suppressed HCoV-229E virus replication. Importantly, the inhibitory effect of LA and AA on virus replication was also conserved for the highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV). Taken together, our study demonstrated that host lipid metabolic remodeling was significantly associated with human-pathogenic coronavirus propagation. Our data further suggested that lipid metabolism regulation would be a common and druggable target for coronavirus infections. Full article

(This article belongs to the Special Issue MERS-CoV)

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12 pages, 2029 KiB

Open AccessArticle

Potent MERS-CoV Fusion Inhibitory Peptides Identified from HR2 Domain in Spike Protein of Bat Coronavirus HKU4

by Shuai Xia, Qiaoshuai Lan, Jing Pu, Cong Wang, Zezhong Liu, Wei Xu, Qian Wang, Huan Liu, Shibo Jiang and Lu Lu

Viruses 2019, 11(1), 56; https://doi.org/10.3390/v11010056 - 14 Jan 2019

Cited by 31 | Viewed by 7435

Abstract

The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and caused continual outbreaks worldwide with high mortality. However, no effective anti-MERS-CoV drug is currently available. Recently, numerous evolutionary studies have suggested that MERS-CoV originated from bat coronavirus (BatCoV). We herein reported that [...] Read more.

The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and caused continual outbreaks worldwide with high mortality. However, no effective anti-MERS-CoV drug is currently available. Recently, numerous evolutionary studies have suggested that MERS-CoV originated from bat coronavirus (BatCoV). We herein reported that three peptides derived from the HR2 region in spike protein of BatCoV HKU4, including HKU4-HR2P1, HKU4-HR2P2 and HKU4-HR2P3, could bind the MERS-CoV HR1-derived peptide to form a six-helix bundle (6-HB) with high stability. Moreover, these peptides, particularly HKU4-HR2P2 and HKU4-HR2P3, exhibited potent inhibitory activity against MERS-CoV S-mediated cell–cell fusion and viral infection, suggesting that these HKU4 HR2-derived peptides could be candidates for futher development as antiviral agents against MERS-CoV infection. Full article

(This article belongs to the Special Issue MERS-CoV)

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13 pages, 2988 KiB

Open AccessArticle

Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV

by Yuting Jiang, Junfeng Li, Yue Teng, Hong Sun, Guang Tian, Lei He, Pei Li, Yuehong Chen, Yan Guo, Jiangfan Li, Guangyu Zhao, Yusen Zhou and Shihui Sun

Viruses 2019, 11(1), 39; https://doi.org/10.3390/v11010039 - 9 Jan 2019

Cited by 63 | Viewed by 7669

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus with a crude mortality rate of ~35%. Previously, we established a human DPP4 transgenic (hDPP4-Tg) mouse model in which we studied complement overactivation-induced immunopathogenesis. Here, to better understand the pathogenesis of MERS-CoV, [...] Read more.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus with a crude mortality rate of ~35%. Previously, we established a human DPP4 transgenic (hDPP4-Tg) mouse model in which we studied complement overactivation-induced immunopathogenesis. Here, to better understand the pathogenesis of MERS-CoV, we studied the role of pyroptosis in THP-1 cells and hDPP4 Tg mice with MERS-CoV infection. We found that MERS-CoV infection induced pyroptosis and over-activation of complement in human macrophages. The hDPP4-Tg mice infected with MERS-CoV overexpressed caspase-1 in the spleen and showed high IL-1β levels in serum, suggesting that pyroptosis occurred after infection. However, when the C5a-C5aR1 axis was blocked by an anti-C5aR1 antibody (Ab), expression of caspase-1 and IL-1β fell. These data indicate that MERS-CoV infection induces overactivation of complement, which may contribute to pyroptosis and inflammation. Pyroptosis and inflammation were suppressed by inhibiting C5aR1. These results will further our understanding of the pathogenesis of MERS-CoV infection. Full article

(This article belongs to the Special Issue MERS-CoV)

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12 pages, 1156 KiB

Open AccessArticle

Combining a Fusion Inhibitory Peptide Targeting the MERS-CoV S2 Protein HR1 Domain and a Neutralizing Antibody Specific for the S1 Protein Receptor-Binding Domain (RBD) Showed Potent Synergism against Pseudotyped MERS-CoV with or without Mutations in RBD

by Cong Wang, Chen Hua, Shuai Xia, Weihua Li, Lu Lu and Shibo Jiang

Viruses 2019, 11(1), 31; https://doi.org/10.3390/v11010031 - 6 Jan 2019

Cited by 21 | Viewed by 5120

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) has continuously posed a threat to public health worldwide, yet no therapeutics or vaccines are currently available to prevent or treat MERS-CoV infection. We previously identified a fusion inhibitory peptide (HR2P-M2) targeting the MERS-CoV S2 protein HR1 [...] Read more.

Middle East respiratory syndrome coronavirus (MERS-CoV) has continuously posed a threat to public health worldwide, yet no therapeutics or vaccines are currently available to prevent or treat MERS-CoV infection. We previously identified a fusion inhibitory peptide (HR2P-M2) targeting the MERS-CoV S2 protein HR1 domain and a highly potent neutralizing monoclonal antibody (m336) specific to the S1 spike protein receptor-binding domain (RBD). However, m336 was found to have reduced efficacy against MERS-CoV strains with mutations in RBD, and HR2P-M2 showed low potency, thus limiting the clinical application of each when administered separately. However, we herein report that the combination of m336 and HR2P-M2 exhibited potent synergism in inhibiting MERS-CoV S protein-mediated cell–cell fusion and infection by MERS-CoV pseudoviruses with or without mutations in the RBD, resulting in the enhancement of antiviral activity in contrast to either one administered alone. Thus, this combinatorial strategy could be used in clinics for the urgent treatment of MERS-CoV-infected patients. Full article

(This article belongs to the Special Issue MERS-CoV)

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18 pages, 2028 KiB

Open AccessArticle

CD8+ T Cells Responding to the Middle East Respiratory Syndrome Coronavirus Nucleocapsid Protein Delivered by Vaccinia Virus MVA in Mice

by Svenja Veit, Sylvia Jany, Robert Fux, Gerd Sutter and Asisa Volz

Viruses 2018, 10(12), 718; https://doi.org/10.3390/v10120718 - 16 Dec 2018

Cited by 36 | Viewed by 5943

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV), a novel infectious agent causing severe respiratory disease and death in humans, was first described in 2012. Antibodies directed against the MERS-CoV spike (S) protein are thought to play a major role in controlling MERS-CoV infection and [...] Read more.

Middle East respiratory syndrome coronavirus (MERS-CoV), a novel infectious agent causing severe respiratory disease and death in humans, was first described in 2012. Antibodies directed against the MERS-CoV spike (S) protein are thought to play a major role in controlling MERS-CoV infection and in mediating vaccine-induced protective immunity. In contrast, relatively little is known about the role of T cell responses and the antigenic targets of MERS-CoV that are recognized by CD8+ T cells. In this study, the highly conserved MERS-CoV nucleocapsid (N) protein served as a target immunogen to elicit MERS-CoV-specific cellular immune responses. Modified Vaccinia virus Ankara (MVA), a safety-tested strain of vaccinia virus for preclinical and clinical vaccine research, was used for generating MVA-MERS-N expressing recombinant N protein. Overlapping peptides spanning the whole MERS-CoV N polypeptide were used to identify major histocompatibility complex class I/II-restricted T cell responses in BALB/c mice immunized with MVA-MERS-N. We have identified a H2-d restricted decamer peptide epitope in the MERS-N protein with CD8+ T cell antigenicity. The identification of this epitope, and the availability of the MVA-MERS-N candidate vaccine, will help to evaluate MERS-N-specific immune responses and the potential immune correlates of vaccine-mediated protection in the appropriate murine models of MERS-CoV infection. Full article

(This article belongs to the Special Issue MERS-CoV)

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20 pages, 5462 KiB

Open AccessArticle

A Human DPP4-Knockin Mouse’s Susceptibility to Infection by Authentic and Pseudotyped MERS-CoV

by Changfa Fan, Xi Wu, Qiang Liu, Qianqian Li, Susu Liu, Jianjun Lu, Yanwei Yang, Yuan Cao, Weijin Huang, Chunnan Liang, Tianlei Ying, Shibo Jiang and Youchun Wang

Viruses 2018, 10(9), 448; https://doi.org/10.3390/v10090448 - 23 Aug 2018

Cited by 45 | Viewed by 6837

Abstract

Infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory illness and has a high mortality rate (~35%). The requirement for the virus to be manipulated in a biosafety level three (BSL-3) facility has impeded development of urgently-needed antiviral agents. Here, we [...] Read more.

Infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory illness and has a high mortality rate (~35%). The requirement for the virus to be manipulated in a biosafety level three (BSL-3) facility has impeded development of urgently-needed antiviral agents. Here, we established anovel mouse model by inserting human dipeptidyl peptidase 4 (hDPP4) into the Rosa26 locus using CRISPR/Cas9, resulting in global expression of the transgene in a genetically stable mouse line. The mice were highly susceptible to infection by MERS-CoV clinical strain hCoV-EMC, which induced severe diffuse pulmonary disease in the animals, and could also be infected by an optimized pseudotyped MERS-CoV. Administration of the neutralizing monoclonal antibodies, H111-1 and m336, as well as a fusion inhibitor peptide, HR2P-M2, protected mice from challenge with authentic and pseudotyped MERS-CoV. These results confirmed that the hDPP4-knockin mouse is a novel model for studies of MERS-CoV pathogenesis and anti-MERS-CoV antiviral agents in BSL-3 and BSL-2facilities, respectively. Full article

(This article belongs to the Special Issue MERS-CoV)

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Review

Jump to: Editorial, Research

14 pages, 1525 KiB

Open AccessReview

Host Determinants of MERS-CoV Transmission and Pathogenesis

by W. Widagdo, Syriam Sooksawasdi Na Ayudhya, Gadissa B. Hundie and Bart L. Haagmans

Viruses 2019, 11(3), 280; https://doi.org/10.3390/v11030280 - 19 Mar 2019

Cited by 61 | Viewed by 12407

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that causes respiratory infection in humans, ranging from asymptomatic to severe pneumonia. In dromedary camels, the virus only causes a mild infection but it spreads efficiently between animals. Differences in the behavior of [...] Read more.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that causes respiratory infection in humans, ranging from asymptomatic to severe pneumonia. In dromedary camels, the virus only causes a mild infection but it spreads efficiently between animals. Differences in the behavior of the virus observed between individuals, as well as between humans and dromedary camels, highlight the role of host factors in MERS-CoV pathogenesis and transmission. One of these host factors, the MERS-CoV receptor dipeptidyl peptidase-4 (DPP4), may be a critical determinant because it is variably expressed in MERS-CoV-susceptible species as well as in humans. This could partially explain inter- and intraspecies differences in the tropism, pathogenesis, and transmissibility of MERS-CoV. In this review, we explore the role of DPP4 and other host factors in MERS-CoV transmission and pathogenesis—such as sialic acids, host proteases, and interferons. Further characterization of these host determinants may potentially offer novel insights to develop intervention strategies to tackle ongoing outbreaks. Full article

(This article belongs to the Special Issue MERS-CoV)

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17 pages, 646 KiB

Open AccessReview

Middle East Respiratory Syndrome Vaccine Candidates: Cautious Optimism

by Craig Schindewolf and Vineet D. Menachery

Viruses 2019, 11(1), 74; https://doi.org/10.3390/v11010074 - 17 Jan 2019

Cited by 67 | Viewed by 10178

Abstract

Efforts towards developing a vaccine for Middle East respiratory syndrome coronavirus (MERS-CoV) have yielded promising results. Utilizing a variety of platforms, several vaccine approaches have shown efficacy in animal models and begun to enter clinical trials. In this review, we summarize the current [...] Read more.

Efforts towards developing a vaccine for Middle East respiratory syndrome coronavirus (MERS-CoV) have yielded promising results. Utilizing a variety of platforms, several vaccine approaches have shown efficacy in animal models and begun to enter clinical trials. In this review, we summarize the current progress towards a MERS-CoV vaccine and highlight potential roadblocks identified from previous attempts to generate coronavirus vaccines. Full article

(This article belongs to the Special Issue MERS-CoV)

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18 pages, 8891 KiB

Open AccessReview

Advances in MERS-CoV Vaccines and Therapeutics Based on the Receptor-Binding Domain

by Yusen Zhou, Yang Yang, Jingwei Huang, Shibo Jiang and Lanying Du

Viruses 2019, 11(1), 60; https://doi.org/10.3390/v11010060 - 14 Jan 2019

Cited by 89 | Viewed by 14589

Abstract

Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is an infectious virus that was first reported in 2012. The MERS-CoV genome encodes four major structural proteins, among which the spike (S) protein has a key role in viral infection and pathogenesis. The receptor-binding domain [...] Read more.

Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is an infectious virus that was first reported in 2012. The MERS-CoV genome encodes four major structural proteins, among which the spike (S) protein has a key role in viral infection and pathogenesis. The receptor-binding domain (RBD) of the S protein contains a critical neutralizing domain and is an important target for development of MERS vaccines and therapeutics. In this review, we describe the relevant features of the MERS-CoV S-protein RBD, summarize recent advances in the development of MERS-CoV RBD-based vaccines and therapeutic antibodies, and illustrate potential challenges and strategies to further improve their efficacy. Full article

(This article belongs to the Special Issue MERS-CoV)

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28 pages, 1385 KiB

Open AccessReview

From SARS to MERS, Thrusting Coronaviruses into the Spotlight

by Zhiqi Song, Yanfeng Xu, Linlin Bao, Ling Zhang, Pin Yu, Yajin Qu, Hua Zhu, Wenjie Zhao, Yunlin Han and Chuan Qin

Viruses 2019, 11(1), 59; https://doi.org/10.3390/v11010059 - 14 Jan 2019

Cited by 842 | Viewed by 68648

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue MERS-CoV)

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15 pages, 1834 KiB

Open AccessReview

Drivers of MERS-CoV Emergence in Qatar

by Elmoubasher Farag, Reina S. Sikkema, Tinka Vinks, Md Mazharul Islam, Mohamed Nour, Hamad Al-Romaihi, Mohammed Al Thani, Muzzamil Atta, Farhoud H. Alhajri, Salih Al-Marri, Mohd AlHajri, Chantal Reusken and Marion Koopmans

Viruses 2019, 11(1), 22; https://doi.org/10.3390/v11010022 - 31 Dec 2018

Cited by 18 | Viewed by 8586

Abstract

MERS-CoV (Middle East respiratory syndrome corona virus) antibodies were detected in camels since 1983, but the first human case was only detected in 2012. This study sought to identify and quantify possible drivers for the MERS-CoV emergence and spillover to humans. A list [...] Read more.

MERS-CoV (Middle East respiratory syndrome corona virus) antibodies were detected in camels since 1983, but the first human case was only detected in 2012. This study sought to identify and quantify possible drivers for the MERS-CoV emergence and spillover to humans. A list of potential human, animal and environmental drivers for disease emergence were identified from literature. Trends in possible drivers were analyzed from national and international databases, and through structured interviews with experts in Qatar. The discovery and exploitation of oil and gas led to a 5-fold increase in Qatar GDP coupled with a 7-fold population growth in the past 30 years. The lifestyle gradually transformed from Bedouin life to urban sedentary life, along with a sharp increase in obesity and other comorbidities. Owing to substantial governmental support, camel husbandry and competitions flourished, exacerbating the already rapidly occurring desertification that forced banning of free grazing in 2005. Consequently, camels were housed in compact barns alongside their workers. The transition in husbandry leading to high density camel farming along with increased exposure to humans, combined with the increase of camel movement for the racing and breeding industry, have led to a convergence of factors driving spillover of MERS-CoV from camels to humans. Full article

(This article belongs to the Special Issue MERS-CoV)

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25 pages, 6053 KiB

Open AccessReview

Development of Small-Molecule MERS-CoV Inhibitors

by Ruiying Liang, Lili Wang, Naru Zhang, Xiaoqian Deng, Meng Su, Yudan Su, Lanfang Hu, Chen He, Tianlei Ying, Shibo Jiang and Fei Yu

Viruses 2018, 10(12), 721; https://doi.org/10.3390/v10120721 - 17 Dec 2018

Cited by 51 | Viewed by 12104

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) with potential to cause global pandemics remains a threat to the public health, security, and economy. In this review, we focus on advances in the research and development of small-molecule MERS-CoV inhibitors targeting different stages of the [...] Read more.

Middle East respiratory syndrome coronavirus (MERS-CoV) with potential to cause global pandemics remains a threat to the public health, security, and economy. In this review, we focus on advances in the research and development of small-molecule MERS-CoV inhibitors targeting different stages of the MERS-CoV life cycle, aiming to prevent or treat MERS-CoV infection. Full article

(This article belongs to the Special Issue MERS-CoV)

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10 pages, 516 KiB

Open AccessReview

Neutralizing Monoclonal Antibodies as Promising Therapeutics against Middle East Respiratory Syndrome Coronavirus Infection

by Hui-Ju Han, Jian-Wei Liu, Hao Yu and Xue-Jie Yu

Viruses 2018, 10(12), 680; https://doi.org/10.3390/v10120680 - 30 Nov 2018

Cited by 15 | Viewed by 5128

Abstract

Since emerging in 2012, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has been a global public health threat with a high fatality rate and worldwide distribution. There are no approved vaccines or therapies for MERS until now. Passive immunotherapy with neutralizing monoclonal antibodies (mAbs) [...] Read more.

Since emerging in 2012, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has been a global public health threat with a high fatality rate and worldwide distribution. There are no approved vaccines or therapies for MERS until now. Passive immunotherapy with neutralizing monoclonal antibodies (mAbs) is an effective prophylactic and therapeutic reagent against emerging viruses. In this article, we review current advances in neutralizing mAbs against MERS-CoV. The receptor-binding domain (RBD) in the spike protein of MERS-CoV is a major target, and mouse, camel, or human-derived neutralizing mAbs targeting RBD have been developed. A major problem with neutralizing mAb therapy is mutant escape under selective pressure, which can be solved by combination of neutralizing mAbs targeting different epitopes. Neutralizing mAbs are currently under preclinical evaluation, and they are promising candidate therapeutic agents against MERS-CoV infection. Full article

(This article belongs to the Special Issue MERS-CoV)

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