Zinc 2+ ion inhibits SARS-CoV-2 main protease and viral replication in vitro

  1. Love Panchariya
  2. Wajahat Ali Khan
  3. Shobhan Kuila
  4. Kirtishila Sonkar
  5. Sibasis Sahoo
  6. Archita Ghoshal
  7. Ankit Kumar
  8. Dileep Kumar Verma
  9. Abdul Hasan
  10. Shubhashis Das
  11. Jitendra K Thakur
  12. Rajkumar Halder
  13. Sujatha Sunil
  14. Arulandu Arockiasamy

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Zinc deficiency is linked to poor prognosis in COVID-19 patients while clinical trials with Zinc demonstrate better clinical outcome. The molecular target and mechanistic details of anti-coronaviral activity of Zinc remain obscure. We show that ionic Zinc not only inhibits SARS-CoV-2 main protease (Mpro) with nanomolar affinity, but also viral replication. We present the first crystal structure of Mpro-Zn 2+ complex at 1.9 Å and provide the structural basis of viral replication inhibition. We show that Zn 2+ coordinates with the catalytic dyad at the enzyme active site along with two previously unknown water molecules in a tetrahedral geometry to form a stable inhibited Mpro-Zn 2+ complex. Further, natural ionophore quercetin increases the anti-viral potency of Zn 2+ . As the catalytic dyad is highly conserved across SARS-CoV, MERS-CoV and all variants of SARS-CoV-2, Zn 2+ mediated inhibition of Mpro may have wider implications.

Article activity feed

  1. Version published to 10.1101/2021.06.15.448551v2 on bioRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.06.15.448551: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: Thank you for sharing your data.

    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.
    • 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.

    Results from scite Reference Check: We found no unreliable references.

    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 10.1101/2021.06.15.448551v1 on bioRxiv
  4. Version published to 10.1039/d1cc03563k