Characterization Of Spike Glycoprotein Of Sars-Cov-2 On Virus Entry And Its Immune Cross-Reactivity With Sars-Cov

Original Article: X Ou, Y Liu, X Lei, P Li, D Mi, L Ren, L Guo, R Guo, T Chen, J Hu, Z Xiang, Z Mu, X Chen, J Chen, K Hu, Q Jin, J Wang & Z Qian, Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV, Nature Communications

Author of summary: Laura Martin; Reviewer: Alessia Villois

Original Article Published on March 27th, 2020

Since 2002, beta coronaviruses (CoV) have caused three disease oubreaks : SARS, MERS, and now COVID-19. However, little is currently known about the biology of SARS-CoV-2. The authors X Ou et al. developed a SARS-CoV-2 pseudovirus system to study, in BSL2 settings, the biology of this virus, mainly focusing on the role of S protein for cell entry.Moreover, the paper presents the results from cross-neutralization tests using recovered SARS and COVID-19 patients’ sera, suggesting that recovery from SARS might not protect against COVID-19 and vice versa.

Purpose:

  • Studying cell type susceptibility, virus receptor, entry pathway, and protease priming for SARS-CoV-2, to hopefully identify potential drug targets
  • Investigating cross-neutralization of SARS-CoV and SARS-CoV-2 using convalescent sera from SARS and COVID-19 patients to provide valuable information for vaccine design.

Methods: Since the virus is categorized as a biosafety level 3 (BSL3) agent, we developed a pseudotype to study virus entry in BSL2 settings.

Results: By using the developed pseudotype system, we confirmed that:

  • SARS-CoV-2
    • has hACE2 as receptor
    • enters 293/hACE2 cells mainly through endocytosis
    • needs PIKfyve, TPC2, and cathepsin L for the entry
  • its S protein
    • is less stable than the one of SARS-CoV
    • could trigger syncytia in 293/hACE2 cells, independently of exogenous protease
  • Sera from recovered SARS patient showed only modest neutralization activity against SARS-CoV-2 S pseudovirions
  • sera from COVID-19 patients did not have any inhibitory effect on transduction by SARS-CoV S pseudovirions

Discussion:

Spike glycoprotein (S) is one of the key components determining virus virulence, tissue tropism and host range, and it is also a main target for neutralizing antibodies and vaccine design. Although the S proteins of SARS-CoV-2 and SARS-CoV are highly homologous, polyclonal rabbit anti-SARS S1 antibodies T62 did not bind to SARS-CoV-2 S protein well and poorly neutralized the virus entry.

We further evaluated cross-neutralization of SARS-CoV and SARS-CoV-2 using convalescent sera from SARS and COVID-19 patients. We only saw moderate cross-neutralization, suggesting that patients previously recovered from SARS-CoV infection may not be fully protected against SARS-CoV-2 infection, and vice versa.– (i.e. patients previously recovered from COVID-19 may not be fully protected against SARS infection).

Conclusion: We characterized SARS-CoV-2 entry in 293/hACE2 cell and demonstrated the important role of S protein. Finally, we found that there is limited cross-neutralization activity between convalescent sera from SARS and COVID-19 patients.            
Our findings provide potential targets for development of drugs and vaccines against this newly emerging lineage B beta-CoV.

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