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10.1128/JVI.01283-20

http://scihub22266oqcxt.onion/10.1128/JVI.01283-20
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32847856!7592233!32847856
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suck abstract from ncbi


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pmid32847856      J+Virol 2020 ; 94 (22): ä
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  • SARS-CoV-2 and Three Related Coronaviruses Utilize Multiple ACE2 Orthologs and Are Potently Blocked by an Improved ACE2-Ig #MMPMID32847856
  • Li Y; Wang H; Tang X; Fang S; Ma D; Du C; Wang Y; Pan H; Yao W; Zhang R; Zou X; Zheng J; Xu L; Farzan M; Zhong G
  • J Virol 2020[Oct]; 94 (22): ä PMID32847856show ga
  • The ongoing coronavirus disease 2019 (COVID-19) pandemic has caused >20 million infections and >750,000 deaths. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, has been found closely related to the bat coronavirus strain RaTG13 (Bat-CoV RaTG13) and a recently identified pangolin coronavirus (Pangolin-CoV-2020). Here, we first investigated the ability of SARS-CoV-2 and three related coronaviruses to utilize animal orthologs of angiotensin-converting enzyme 2 (ACE2) for cell entry. We found that ACE2 orthologs of a wide range of domestic and wild mammals, including camels, cattle, horses, goats, sheep, cats, rabbits, and pangolins, were able to support cell entry of SARS-CoV-2, suggesting that these species might be able to harbor and spread this virus. In addition, the pangolin and bat coronaviruses, Pangolin-CoV-2020 and Bat-CoV RaTG13, were also found able to utilize human ACE2 and a number of animal-ACE2 orthologs for cell entry, indicating risks of spillover of these viruses into humans in the future. We then developed potently anticoronavirus ACE2-Ig proteins that are broadly effective against the four distinct coronaviruses. In particular, through truncating ACE2 at its residue 740 but not 615, introducing a D30E mutation, and adopting an antibody-like tetrameric-ACE2 configuration, we generated an ACE2-Ig variant that neutralizes SARS-CoV-2 at picomolar range. These data demonstrate that the improved ACE2-Ig variants developed in this study could potentially be developed to protect from SARS-CoV-2 and some other SARS-like viruses that might spillover into humans in the future.IMPORTANCE The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the currently uncontrolled coronavirus disease 2019 (COVID-19) pandemic. It is important to study the host range of SARS-CoV-2, because some domestic species might harbor the virus and transmit it back to humans. In addition, insight into the ability of SARS-CoV-2 and SARS-like viruses to utilize animal orthologs of the SARS-CoV-2 receptor ACE2 might provide structural insight into improving ACE2-based viral entry inhibitors. In this study, we found that ACE2 orthologs of a wide range of domestic and wild animals can support cell entry of SARS-CoV-2 and three related coronaviruses, providing insights into identifying animal hosts of these viruses. We also developed recombinant ACE2-Ig proteins that are able to potently block these viral infections, providing a promising approach to developing antiviral proteins broadly effective against these distinct coronaviruses.
  • |Angiotensin-Converting Enzyme 2[MESH]
  • |Animals[MESH]
  • |Antibodies, Neutralizing/chemistry/*genetics[MESH]
  • |Betacoronavirus/genetics/*physiology[MESH]
  • |Coronavirus/*classification/genetics/physiology[MESH]
  • |Disease Models, Animal[MESH]
  • |HEK293 Cells[MESH]
  • |Humans[MESH]
  • |Immunoglobulins/chemistry/genetics[MESH]
  • |Models, Chemical[MESH]
  • |Peptidyl-Dipeptidase A/chemistry/genetics/metabolism[MESH]
  • |Receptors, Virus/chemistry/genetics[MESH]
  • |Recombinant Proteins/genetics[MESH]
  • |SARS-CoV-2[MESH]


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