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Abstract
The source of the severe acute respiratory syndrome (SARS) epidemic was traced to
wildlife market civets and ultimately to bats. Subsequent hunting for novel coronaviruses
(CoVs) led to the discovery of two additional human and over 40 animal CoVs, including
the prototype lineage C betacoronaviruses, Tylonycteris bat CoV HKU4 and Pipistrellus
bat CoV HKU5; these are phylogenetically closely related to the Middle East respiratory
syndrome (MERS) CoV, which has affected more than 1,000 patients with over 35% fatality
since its emergence in 2012. All primary cases of MERS are epidemiologically linked
to the Middle East. Some of these patients had contacted camels which shed virus and/or
had positive serology. Most secondary cases are related to health care-associated
clusters. The disease is especially severe in elderly men with comorbidities. Clinical
severity may be related to MERS-CoV's ability to infect a broad range of cells with
DPP4 expression, evade the host innate immune response, and induce cytokine dysregulation.
Reverse transcription-PCR on respiratory and/or extrapulmonary specimens rapidly establishes
diagnosis. Supportive treatment with extracorporeal membrane oxygenation and dialysis
is often required in patients with organ failure. Antivirals with potent in vitro
activities include neutralizing monoclonal antibodies, antiviral peptides, interferons,
mycophenolic acid, and lopinavir. They should be evaluated in suitable animal models
before clinical trials. Developing an effective camel MERS-CoV vaccine and implementing
appropriate infection control measures may control the continuing epidemic.
A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.
Spike (S) proteins of coronaviruses, including the coronavirus that causes severe acute respiratory syndrome (SARS), associate with cellular receptors to mediate infection of their target cells 1,2 . Here we identify a metallopeptidase, angiotensin-converting enzyme 2 (ACE2) 3,4 , isolated from SARS coronavirus (SARS-CoV)-permissive Vero E6 cells, that efficiently binds the S1 domain of the SARS-CoV S protein. We found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells. 293T cells transfected with ACE2, but not those transfected with human immunodeficiency virus-1 receptors, formed multinucleated syncytia with cells expressing S protein. Furthermore, SARS-CoV replicated efficiently on ACE2-transfected but not mock-transfected 293T cells. Finally, anti-ACE2 but not anti-ACE1 antibody blocked viral replication on Vero E6 cells. Together our data indicate that ACE2 is a functional receptor for SARS-CoV. Supplementary information The online version of this article (doi:10.1038/nature02145) contains supplementary material, which is available to authorized users.
A novel coronavirus (SCoV) is the etiological agent of severe acute respiratory syndrome (SARS). SCoV-like viruses were isolated from Himalayan palm civets found in a live-animal market in Guangdong, China. Evidence of virus infection was also detected in other animals (including a raccoon dog, Nyctereutes procyonoides) and in humans working at the same market. All the animal isolates retain a 29-nucleotide sequence that is not found in most human isolates. The detection of SCoV-like viruses in small, live wild mammals in a retail market indicates a route of interspecies transmission, although the natural reservoir is not known.
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