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Broad and Differential Animal Angiotensin-Converting Enzyme 2 Receptor Usage by SARS-CoV-2.
Xuesen Zhao1,2, Danying Chen3,2, Robert Szabla4
1Institute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, China zhaoxuesen@ccmu.edu.cn hanxin.lin@lhsc.on.ca.
Journal of Virology
|July 15, 2020
Summary
Scientists investigated how SARS-CoV-2 infects animals. They found that the virus can use angiotensin-converting enzyme 2 (ACE2) from many species, suggesting broad potential for animal hosts and transmission.
Area of Science:
- Virology
- Zoonotic Diseases
- Molecular Biology
Background:
- The COVID-19 pandemic, caused by SARS-CoV-2, has had severe global health and economic impacts.
- The precise origins of SARS-CoV-2 and its transmission pathways remain under investigation, with bats and pangolins previously suggested as reservoirs.
- A unique feature of SARS-CoV-2, absent in related coronaviruses from bats and pangolins, is a polybasic furin cleavage site in its spike (S) glycoprotein.
Purpose of the Study:
- To identify potential intermediate or amplifying animal hosts for SARS-CoV-2.
- To investigate the receptor activity of angiotensin-converting enzyme 2 (ACE2) from various mammal species for SARS-CoV-2 entry.
- To understand the role of the S protein and ACE2 interaction in interspecies transmission and host tropism.
Main Methods:
- Examined the ACE2 receptor activity across 14 mammal species.
- Utilized lentiviral particles pseudotyped with SARS-CoV-2 spike (S) proteins (wild-type and furin cleavage site-deficient).
- Assessed binding affinity of the S1 subunit of the SARS-CoV-2 S protein to different species' ACE2.
Main Results:
- ACE2 from multiple mammal species supported infectious entry of pseudotyped SARS-CoV-2.
- Human/rhesus monkey ACE2 showed the highest receptor activity, while rat/mouse ACE2 exhibited the lowest.
- Rabbit and pangolin ACE2 demonstrated strong binding to the S1 subunit and efficient support of viral infection.
Conclusions:
- SARS-CoV-2 can utilize ACE2 from a wide array of animal species for cell entry, irrespective of the furin cleavage site.
- Findings suggest broader implications for natural host reservoirs, zoonotic and human-to-animal transmission dynamics.
- The study highlights the importance of ACE2-S protein interactions in determining host range and informs the selection and use of animal models for SARS-CoV-2 research.
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