On the interactions of the receptor-binding domain of SARS-CoV-1 and SARS-CoV-2 spike proteins with monoclonal antibodies and the receptor ACE2

  1. Carolina Corrêa Giron
  2. Aatto Laaksonen
  3. Fernando L. Barroso da Silva

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Abstract

A new betacoronavirus named SARS-CoV-2 has emerged as a new threat to global health and economy. A promising target for both diagnosis and therapeutics treatments of the new disease named COVID-19 is the coronavirus (CoV) spike (S) glycoprotein. By constant-pH Monte Carlo simulations and the PROCEEDpKa method, we have mapped the electrostatic epitopes for four monoclonal antibodies and the angiotensin-converting enzyme 2 (ACE2) on both SARS-CoV-1 and the new SARS-CoV-2 S receptor binding domain (RBD) proteins. We also calculated free energy of interactions and shown that the S RBD proteins from both SARS viruses binds to ACE2 with similar affinities. However, the affinity between the S RBD protein from the new SARS-CoV-2 and ACE2 is higher than for any studied antibody previously found complexed with SARS-CoV-1. Based on physical chemical analysis and free energies estimates, we can shed some light on the involved molecular recognition processes, their clinical aspects, the implications for drug developments, and suggest structural modifications on the CR3022 antibody that would improve its binding affinities for SARS-CoV-2 and contribute to address the ongoing international health crisis.

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    SciScore for 10.1101/2020.04.05.026377: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The “UCSF Chimera 1.11.2” package45 was employed for all molecular visualizations and representations too.
    Chimera
    suggested: (Chimera, RRID:SCR_002959)
    The pairwise sequence alignments were generated by the server EMBOSS Needle68 with default settings.
    EMBOSS
    suggested: (EMBOSS, RRID:SCR_008493)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    We are careful with the use of stronger statements here due to the limitation of the theoretical approach. Several additional issues remain to be further investigated. Finally, we compared the EE predictions for CR3022’ (34 aa) with CR3022 (33 aa) interacting with SARS-CoV-2 S RBD protein − see Figure 10. The predicted EEs for the interaction with CR3022’ are essentially the same ones observed for CR3022 (27 common aa). This implies that the suggested mutations here do not affected the antigenic regions. Another particularly interesting feature of this computer-designed molecule is that the number of EEs shared with ACE2 has increased from 18 (for CR3022) to 27 (for CR3022’). This might amplify the potential of this mAb candidate to better block the virus-host cell interaction.

    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: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • No conflict of interest statement was detected. If there are no conflicts, we encourage authors to explicit state so.
    • 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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  2. Version published to 10.1101/2020.04.05.026377 on bioRxiv