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 Here we identify a metallopeptidase, angiotensin-converting enzyme 2 (ACE2), 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

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Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus.

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.

http://iacld.ir/DL/elm/isolationofanovelcoronavirusfromamanwithpneumoniainsaudiarabia.pdf

Isolation of a Novel Coronavirus from a Man with Pneumonia in Saudi Arabia

During several months of 2003, a newly identified illness termed severe acute respiratory syndrome (SARS) spread rapidly through the world. A new coronavirus (SARS-CoV) was identified as the SARS pathogen, which triggered severe pneumonia and acute, often lethal, lung failure. Moreover, among infected individuals influenza such as the Spanish flu and the emergence of new respiratory disease viruses have caused high lethality resulting from acute lung failure. In cell lines, angiotensin-converting enzyme 2 (ACE2) has been identified as a potential SARS-CoV receptor. The high lethality of SARS-CoV infections, its enormous economic and social impact, fears of renewed outbreaks as well as the potential misuse of such viruses as biologic weapons make it paramount to understand the pathogenesis of SARS-CoV. Here we provide the first genetic proof that ACE2 is a crucial SARS-CoV receptor in vivo. SARS-CoV infections and the Spike protein of the SARS-CoV reduce ACE2 expression. Notably, injection of SARS-CoV Spike into mice worsens acute lung failure in vivo that can be attenuated by blocking the renin-angiotensin pathway. These results provide a molecular explanation why SARS-CoV infections cause severe and often lethal lung failure and suggest a rational therapy for SARS and possibly other respiratory disease viruses.

/pdf/a-crucial-role-of-angiotensin-converting-enzyme-2-ace2-in-2d22di484z.pdf

A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury

Severe acute respiratory syndrome (SARS) emerged in 2002 to 2003 in southern China. The origin of its etiological agent, the SARS coronavirus (SARS-CoV), remains elusive. Here we report that species of bats are a natural host of coronaviruses closely related to those responsible for the SARS outbreak. These viruses, termed SARS-like coronaviruses (SL-CoVs), display greater genetic variation than SARS-CoV isolated from humans or from civets. The human and civet isolates of SARS-CoV nestle phylogenetically within the spectrum of SL-CoVs, indicating that the virus responsible for the SARS outbreak was a member of this coronavirus group.

/pdf/bats-are-natural-reservoirs-of-sars-like-coronaviruses-313upjkru9.pdf

Bats are natural reservoirs of SARS-like coronaviruses.

The severe acute respiratory syndrome (SARS) is responsible for the first pandemic of the 21st century. Within months after its emergence in Guangdong Province in mainland China, it had affected more than 8000 patients and caused 774 deaths in 26 countries on five continents. It illustrated dramatically the potential of air travel and globalization for the dissemination of an emerging infectious disease and highlighted the need for a coordinated global response to contain such disease threats. We review the cause, epidemiology, and clinical features of the disease.

/pdf/the-severe-acute-respiratory-syndrome-29m26drr2u.pdf

The severe acute respiratory syndrome.

In March 2003, a novel coronavirus (SARS-CoV) was discovered in association with cases of severe acute respiratory syndrome (SARS). The sequence of the complete genome of SARS-CoV was determined, and the initial characterization of the viral genome is presented in this report. The genome of SARS-CoV is 29,727 nucleotides in length and has 11 open reading frames, and its genome organization is similar to that of other coronaviruses. Phylogenetic analyses and sequence comparisons showed that SARS-CoV is not closely related to any of the previously characterized coronaviruses.

/pdf/characterization-of-a-novel-coronavirus-associated-with-51t7indirj.pdf

Characterization of a novel coronavirus associated with severe acute respiratory syndrome.

A sixteenth haemagglutinin subtype of influenza A virus (H16) has been isolated from gulls in Sweden and the Netherlands The invention provides the new virus, its haemagglutinin protein and nucleic acid encoding the same These are particularly useful for vaccination Of the fifteen known subtypes H1 to H15, this subtype is most closely related to H13

Influenza a virus subtype h16

Severe Acute Respiratory Syndrome: Peiris/Severe

Aetiology of SARS

Sub-lethal effects of low-pathogenic influenza A virus infection in mallards (Anas platyrhynchos) caught on autumn migration in Ottenby, Sweden

Albert Osterhaus

Papers

Characterization of a novel coronavirus associated with severe acute respiratory syndrome.

Influenza a virus subtype h16

Severe Acute Respiratory Syndrome: Peiris/Severe

Aetiology of SARS

Sub-lethal effects of low-pathogenic influenza A virus infection in mallards (Anas platyrhynchos) caught on autumn migration in Ottenby, Sweden