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.

/pdf/from-sars-to-mers-thrusting-coronaviruses-into-the-spotlight-4yt0tzjx7o.pdf

From SARS to MERS, Thrusting Coronaviruses into the Spotlight

The emergence of severe acute respiratory syndrome (SARS) coronavirus and, more recently, Middle East respiratory syndrome (MERS) coronavirus has highlighted the pathogenic and epidemic potential of this virus family. Here, Graham, Donaldson and Baric review key biological properties of coronaviruses and how to target them with potential therapeutics. Two novel coronaviruses have emerged in humans in the twenty-first century: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), both of which cause acute respiratory distress syndrome (ARDS) and are associated with high mortality rates. There are no clinically approved vaccines or antiviral drugs available for either of these infections; thus, the development of effective therapeutic and preventive strategies that can be readily applied to new emergent strains is a research priority. In this Review, we describe the emergence and identification of novel human coronaviruses over the past 10 years, discuss their key biological features, including tropism and receptor use, and summarize approaches for developing broadly effective vaccines.

/pdf/a-decade-after-sars-strategies-for-controlling-emerging-2mwklf6q7g.pdf

A decade after SARS: strategies for controlling emerging coronaviruses

From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.

Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in early 2003 to cause a very severe acute respiratory syndrome, which eventually resulted in a 10% case-fatality rate. Owing to excellent public health measures that isolated focus cases and their contacts, and the use of supportive therapies, the epidemic was suppressed to the point that further cases have not appeared since 2005. However, despite intensive research since then (over 3500 publications), it remains an untreatable disease. The potential for re-emergence of the SARS-CoV or a similar virus with unknown but potentially serious consequences remains high. This is due in part to the extreme genetic variability of RNA viruses such as the coronaviruses, the many animal reservoirs that seem to be able host the SARS-CoV in which reassortment or recombination events could occur and the ability coronaviruses have to transmit relatively rapidly from species to species in a short period of time. Thus, it seems prudent to continue to explor...

/pdf/recent-developments-in-anti-severe-acute-respiratory-3rnlmsnqzl.pdf

Recent developments in anti-severe acute respiratory syndrome coronavirus chemotherapy

Phagocytic cells contribute to the antibody-mediated elimination of pulmonary-infected SARS coronavirus

Equine anti-severe acute respiratory syndrome-associated coronavirus F(ab')(2) has been verified to protect mice from infection with severe acute respiratory syndrome-associated coronavirus (SARS-CoV). However, before potential clinical application, the antibody needs to be tested in as many animal models as possible to ensure its safety and efficiency. In this study, after verification by various methods that the golden Syrian hamster constitutes a model susceptible to SARS-CoV infection, we confirmed that the antibody could protect animals completely from SARS-CoV infection in the preventive setting. More importantly, the antibody could reduce viral titers or copies by approximately 10(3)- to 10(4)-fold in animal lung after virus exposure, compared with negative control. These data provide further evidence to warrant clinical studies of this antibody in the treatment and prevention of SARS.

Inhibition of Severe Acute Respiratory Syndrome-Associated Coronavirus Infection by Equine Neutralizing Antibody in Golden Syrian Hamsters

To warrant potential clinical testing, the equine anti-severe acute respiratory syndrome coronavirus (SARS-CoV) F(ab')(2) requires evaluation in as many animal models as possible. In this study, we established a new animal model, the Chinese hamster, susceptible to SARS-CoV infection. SARS-CoV could propagate effectively and sustain high levels for 1 wk in animal lungs. All animals were protected from SARS-CoV infection in preventive settings. Further, when used therapeutically this antibody led to an approximately 4-log(10) decrease in viral burden in infected animal lungs. The pathological changes in lungs correlated closely with the dose of antibody administered. The excellent preventive and therapeutic roles of equine anti-SARS-CoV F(ab')(2) in several animal models, including the novel Chinese hamster model described in this study, have provided exciting data concerning its potential clinical study.

Protection from infection with severe acute respiratory syndrome coronavirus in a Chinese hamster model by equine neutralizing F(ab')2.

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Inhibition of Severe Acute Respiratory Syndrome-Associated Coronavirus Infection by Equine Neutralizing Antibody in Golden Syrian Hamsters

Protection from infection with severe acute respiratory syndrome coronavirus in a Chinese hamster model by equine neutralizing F(ab')2.