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Study · In vitro (cell-free) · 2020

5 results

In silico Analysis Revealed Potential Anti-SARS-CoV-2 Main Protease Activity by the Zonulin Inhibitor Larazotide Acetate.

Di Micco S, Musella S, Scala MC, Sala M, Campiglia P, Bifulco G, Fasano A

Frontiers in chemistry15 Jan 2021Cited by 21 (Europe PMC)

PMID33520943 (opens in a new tab)PMCIDPMC7843458 (opens in a new tab)DOI10.3389/fchem.2020.628609 (opens in a new tab)PepBankPUB-33520943
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Summary

The most severe outcome of COVID-19 infection is the development of interstitial pneumonia causing acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS), both responsible for the infected patients' mortality. ALI and ARDS are characterized by a leakage of plasma components into the lungs, compromising their ability to expand and optimally engage in gas exchange with blood, resulting in respiratory failure. We have previously reported that zonulin, a protein dictating epithelial and endothelial permeability in several districts, including the airways, is involved in ALI pathogenesis in mouse models, and that its peptide inhibitor Larazotide acetate (also called AT1001) ameliorated ALI and subsequent mortality by decreasing mucosal permeability to fluid and extravasation of neutrophils into the lungs. With the recent crystallographic resolution of the SARS-CoV-2 main protease (Mpro), an enzyme fundamental in the viral lifecycle, bound to peptidomimetic inhibitors N3 and 13b, we were able to perform molecular modeling investigation showing that AT1001 presents structural motifs similar to co-crystallized ligands. Specifically, molecular docking, MM-GBSA-based predictions and molecular dynamics showed that AT1001 docks extremely well in the Mpro catalytic domain through a global turn conformational arrangement without any unfavorable steric hindrance. Finally, we have observed that AT1001 can be superimposed onto the crystallized structures of N3 and 13b, establishing a higher number of interactions and accordingly a tighter binding. In vitro studies confirmed AT1001 anti-Mpro and preliminary investigation indicted an anti-viral activity. Combined, these studies suggest that AT1001, besides its well-demonstrated effect in ameliorating mucosal permeability in ALI/ARDS, may also exert a direct anti-SARS-CoV-2 effect by blocking the Mpro. AT1001 has been used extensively in a variety of animal models of ALI demonstrating robust safety and efficacy; it is currently in phase 3 trials in celiac subjects showing strong safety and efficacy profiles. We therefore propose its use as a specific anti-SARS-CoV-2 multitargeting treatment for the current pandemic.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

2 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cell-free)Activity measurement

    In vitro, AT1001 showed activity against the SARS-CoV-2 main protease.

    In plain wordsIn lab tests, AT1001 showed activity against the viral main protease.

    Peptide
    Larazotide
    Outcome
    DecreaseMain protease inhibition
    Study

    n: not reported in source

    SARS-CoV-2 main protease
    Outcome group
    Antiviral activity · Infection
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In vitro studies confirmed AT1001 anti-Mpro and preliminary investigation indicted an anti-viral activity.
  2. 02LabOther designActivity measurement

    In preliminary laboratory tests, AT1001 showed antiviral activity.

    In plain wordsIn lab tests, AT1001 showed preliminary antiviral activity.

    Peptide
    Larazotide
    Outcome
    Direction not reportedPreliminary antiviral activity
    Study

    n: not reported in source

    Outcome group
    Antiviral activity · Infection
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In vitro studies confirmed AT1001 anti-Mpro and preliminary investigation indicted an anti-viral activity.

Studies that did not test the peptide alone3

In this study, Larazotide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Larazotide.

  1. 03Computer modelNot a test of Larazotide aloneIn silicoMechanism

    In molecular models, AT1001 had structural motifs similar to co-crystallized protease ligands.

    In plain wordsIn computer models, AT1001 had structural features similar to ligands bound to the viral protease.

    Peptide
    Larazotide
    Outcome
    Not applicableStructural motifs
    Study

    n: not reported in source

    SARS-CoV-2 main protease
    Outcome group
    Receptor activity and mechanism · Pharmacology

    Source sentences

    Summary
    we were able to perform molecular modeling investigation showing that AT1001 presents structural motifs similar to co-crystallized ligands.

    In this study, Larazotide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Larazotide.

  2. 04Computer modelNot a test of Larazotide aloneIn silicoMechanism

    In molecular models, AT1001 docked in the main protease catalytic domain without unfavorable steric hindrance.

    In plain wordsIn computer models, AT1001 fitted the viral protease catalytic domain without unfavorable steric hindrance.

    Peptide
    Larazotide
    Outcome
    Not applicableCatalytic-domain docking
    Study

    n: not reported in source

    SARS-CoV-2 main protease
    Outcome group
    Receptor activity and mechanism · Pharmacology

    Source sentences

    Summary
    Specifically, molecular docking, MM-GBSA-based predictions and molecular dynamics showed that AT1001 docks extremely well in the Mpro catalytic domain through a global turn conformational arrangement without any unfavorable steric hindrance.

    In this study, Larazotide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Larazotide.

  3. 05Computer modelNot a test of Larazotide aloneIn silicoMechanism

    In structural models, AT1001 established more interactions and tighter binding than N3 and 13b.

    In plain wordsIn computer models, AT1001 formed more interactions and bound more tightly than N3 and 13b.

    Peptide
    Larazotide
    Outcome
    IncreaseProtease binding interactions
    Study

    n: not reported in source

    SARS-CoV-2 main protease
    Comparator
    N3 and 13b
    Outcome group
    Receptor activity and mechanism · Pharmacology

    Source sentences

    Summary
    Finally, we have observed that AT1001 can be superimposed onto the crystallized structures of N3 and 13b, establishing a higher number of interactions and accordingly a tighter binding.

    In this study, Larazotide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Larazotide.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    22 Oct 2026, 02:26 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 18:59 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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