Coronavirus hemagglutinin-esterase and spike proteins coevolve for functional balance and optimal virion avidity
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Abstract
Human coronavirus OC43 arose relatively recently, presumably from a bovine coronavirus spillover. Both viruses use 9- O -acetylated sialoglycans as receptors to which they attach via spike protein S. Another envelope protein, hemagglutinin-esterase (HE), serves as a receptor-destroying enzyme. We demonstrate that HE and S are functionally intertwined and that receptor destruction and receptor binding need to be carefully balanced for efficient (pre)attachment. During early emergence of OC43 this balance was reset, presumably as an adaptation to the human host. Such a two-protein mechanism for dynamic virion attachment is unique among coronaviruses, but reminiscent of that of influenza A viruses. Apparently, general principles fundamental to virion–sialoglycan interactions prompted convergent evolution of two zoonotically-relevant groups of pathogens.
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SciScore for 10.1101/2020.04.03.003699: (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
Experimental Models: Cell Lines Sentences Resources Expression and purification of HE-Fc and S1A-Fc proteins: BCoV HE, either enzymatically-active (HE+) or rendered inactive through a Ser40Ala substitution (HE0), and OC43 S1A were expressed as Fc fusion proteins in HEK293T cells and purified from the cell supernatant by protein A affinity chromatography as detailed17,32. HEK293Tsuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers …
SciScore for 10.1101/2020.04.03.003699: (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
Experimental Models: Cell Lines Sentences Resources Expression and purification of HE-Fc and S1A-Fc proteins: BCoV HE, either enzymatically-active (HE+) or rendered inactive through a Ser40Ala substitution (HE0), and OC43 S1A were expressed as Fc fusion proteins in HEK293T cells and purified from the cell supernatant by protein A affinity chromatography as detailed17,32. HEK293Tsuggested: NoneResults 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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
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