Prefusion conformation of SARS-CoV-2 receptor-binding domain favours interactions with human receptor ACE2

  1. Nitesh Kumawat
  2. Andrejs Tucs
  3. Soumen Bera
  4. Gennady N. Chuev
  5. Marina V. Fedotova
  6. Koji Tsuda
  7. Sergey E. Kruchinin
  8. Adnan Sljoka
  9. Amit Chakraborty

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

A new coronavirus pandemic COVID-19, caused by Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2), poses a serious threat across continents, leading the World Health Organization to declare a Public Health Emergency of International Concern. In order to block the entry of the virus into human host cells, major therapeutic and vaccine design efforts are now targeting the interactions between the SARS-CoV-2 spike (S) glycoprotein and the human cellular membrane receptor angiotensin-converting enzyme, hACE2. By analyzing cryo-EM structures of SARS-CoV-2 and SARS-CoV-1, we report here that the homotrimer SARS-CoV-2 S receptor-binding domain (RBD) that binds with hACE2 has expanded in size, undergoing a large conformational change relative to SARS-CoV-1 S protein. Protomer with the up-conformational form of RBD, which binds with hACE2, exhibits higher intermolecular interactions at the RBD-ACE2 interface, with differential distributions and the inclusion of specific H-bonds in the CoV-2 complex. Further interface analysis has shown that interfacial water promotes and stabilizes the formation of CoV-2/hACE2 complex. This interaction has caused a significant structural rigidification, favoring proteolytic processing of S protein for the fusion of the viral and cellular membrane. Moreover, conformational dynamics simulations of RBD motions in SARS-CoV-2 and SARS-CoV-1 point to the role in modification in the RBD dynamics and their likely impact on infectivity.

Article activity feed

  1. Version published to 10.1101/2021.04.22.441041v2 on bioRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.04.22.441041: (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
    Constrained geometric simulations for conformational sampling: To study dynamics of the considered structures, we employed a low computational complexity alternative to MD geometric molecular simulation package FRODAN v1.0.1 [10].
    FRODAN
    suggested: None
    Before running simulations, hydrogen bonds to each considered structure were added using MolProbity server: (http://molprobity.biochem.duke.edu/).
    MolProbity
    suggested: (MolProbity, RRID:SCR_014226)
    The 3D-RISM calculations were performed using the rism3d.snglpnt codes from the AmberTools 16 package [39].
    AmberTools
    suggested: (AmberTools, RRID:SCR_018497)

    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: 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.
    • 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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.04.22.441041v1 on bioRxiv