Cell entry of SARS-CoV-2 conferred by angiotensin-converting enzyme 2 (ACE2) of different species
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Abstract
The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a huge threat to many countries around the world. However, where is it origin and which animals are sensitive to cross-species transmission is unclear. The interaction of virus and cell receptor is a key determinant of host range for the novel coronavirus. Angiotensin-converting enzyme 2 (ACE2) is demonstrated as the primary entry receptor for SARS-CoV-2. In this study, we evaluated the SARS-CoV-2 entry mediated by ACE2 of 11 different species of animals, and discovered that ACE2 of Rhinolophus sinicus (Chinese horseshoe bat), Felis catus (domestic cat), Canis lupus familiaris (dog), Sus scrofa (pig), Capra hircus (goat) and especially Manis javanica (Malayan pangolin) were able to render SARS-CoV-2 entry in non-susceptible cells. This is the first report that ACE2 of Pangolin could mediate SARS-CoV-2 entry which increases the presume that SARS-CoV-2 may have a pangolin origin. However, none of the ACE2 proteins from Rhinolophus ferrumequinum (greater horseshoe bat), Gallus gallus (chicken), Notechis scutatus (mainland tiger snake), Mus musculus (house mouse) rendered SARS-CoV-2 entry. Specifically, a natural isoform of Macaca mulatta (Rhesus monkey) ACE2 with a mutation of Y217N was resistance to infection, which rises the possible impact of this type of ACE2 during monkey studies of SARS-CoV-2. Overall, these results clarify that SARS-CoV-2 could engage receptors of multiple species of animals and it is a perplexed work to track SARS-CoV-2 origin and its intermediate hosts.
IMPORTANCE
In this study, we illustrated that SARS-CoV-2 is able to engage receptors of multiple species of animals. This indicated that it may be a perplexed work to track SARS-CoV-2 origin and discover its intermediate hosts. This feature of virus is considered to potentiate its diverse cross-species transmissibility. Of note, here is the first report that ACE2 of Pangolin could mediate SARS-CoV-2 entry which increases the possibility that SARS-CoV-2 may have a pangolin origin. And we also demonstrated that not all species of bat were sensitive to SARS-CoV-2 infection. At last, it is also important to detect the expression ratio of the Y217N ACE2 to the prototype in Rhesus monkeys to be recruited for studies on SARS-CoV-2 infection.
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SciScore for 10.1101/2020.06.15.153916: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The nucleoprotein (N) of SARS-CoV was detected for infection and replication of the virus using an N-specific polyclonal antibody (Sinobiological, China), and a donkey anti-rabbit IgG (H+L) labeled with Cy3 (Jacksion, USA) was used as the secondary antibody. anti-rabbit IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources Cells and SARS-CoV-2: HEK293T cells cells were maintained in DMEM (Gibco, USA) with 10% fetal bovine serum (HyClone, USA). H…SciScore for 10.1101/2020.06.15.153916: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources The nucleoprotein (N) of SARS-CoV was detected for infection and replication of the virus using an N-specific polyclonal antibody (Sinobiological, China), and a donkey anti-rabbit IgG (H+L) labeled with Cy3 (Jacksion, USA) was used as the secondary antibody. anti-rabbit IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources Cells and SARS-CoV-2: HEK293T cells cells were maintained in DMEM (Gibco, USA) with 10% fetal bovine serum (HyClone, USA). HEK293Tsuggested: NoneSoftware and Algorithms Sentences Resources Sequence analysis: ACE2 sequences of 12 different species were acquired from NCBI and their alignment were assessed using the ClustalW method in Lasergene software (Version 7.1) (DNASTAR Inc., USA). ClustalWsuggested: (ClustalW, RRID:SCR_017277)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on pages 20 and 21. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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