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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Virology
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1443183

Hyperforin, the major metabolite of St. John's wort, exhibits pancoronavirus activity

Provisionally accepted
Imelda Raczkiewicz Imelda Raczkiewicz 1Céline Rivière Céline Rivière 2Peggy Bouquet Peggy Bouquet 1Lowiese Desmarets Lowiese Desmarets 1Audrey Tarricone Audrey Tarricone 1Charline Camuzet Charline Camuzet 1Nathan François Nathan François 1Gabriel Lefèvre Gabriel Lefèvre 2Fabiola Silva Angulo Fabiola Silva Angulo 1Cyril Robil Cyril Robil 1François TROTTEIN François TROTTEIN 1Sevser Sahpaz Sevser Sahpaz 2Jean Dubuisson Jean Dubuisson 1Sandrine Belouzard Sandrine Belouzard 1Anne Goffard Anne Goffard 1Karin Séron Karin Séron 1*
  • 1 INSERM U1019 Centre d'Infection et Immunité de Lille (CIIL), Lille, Nord-Pas-de-Calais, France
  • 2 Université de Lille, Lille, Nord-Pas-de-Calais, France

The final, formatted version of the article will be published soon.

    The COVID-19 pandemic caused by the SARS-CoV-2 virus has underscored the urgent necessity for the development of antiviral compounds that can effectively target coronaviruses. In this study, we present the first evidence of the antiviral efficacy of hyperforin, a major metabolite of St. John's wort, for which safety and bioavailability in humans have already been established. Antiviral assays were conducted in cell culture with four human coronaviruses: three of high virulence, SARS-CoV-2, SARS-CoV, and MERS-CoV, and one causing mild symptoms, HCoV-229E. The antiviral activity was also evaluated in human primary airway epithelial cells. To ascertain the viral step inhibited by hyperforin, time-of-addition assays were conducted. Subsequently, a combination assay of hyperforin with remdesivir was performed. The results demonstrated that hyperforin exhibited notable antiviral activity against the four tested human coronaviruses, with IC50 values spanning from 0.24 to 2.55 µM. Kinetic studies indicated that the observed activity occur at a post-entry step, potentially during replication. The antiviral efficacy of hyperforin was additionally corroborated in human primary airway epithelial cells. The results demonstrated a reduction in both intracellular and extracellular SARS-CoV-2 viral RNA, confirming that hyperforin targeted the replication step. Finally, an additive antiviral effect on SARS-CoV-2 was observed when hyperforin was combined with remdesivir. In conclusion, hyperforin has been identified as a novel pan-coronavirus inhibitor with activity in human primary airway epithelial cells, a preclinical model for coronaviruses. These findings collectively suggest that hyperforin has potential as a candidate antiviral agent against current and future human coronaviruses..

    Keywords: Coronaviruses, antiviral, natural compound, Replication, Broad-spectrum

    Received: 03 Jun 2024; Accepted: 29 Jul 2024.

    Copyright: © 2024 Raczkiewicz, Rivière, Bouquet, Desmarets, Tarricone, Camuzet, François, Lefèvre, Silva Angulo, Robil, TROTTEIN, Sahpaz, Dubuisson, Belouzard, Goffard and Séron. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Karin Séron, INSERM U1019 Centre d'Infection et Immunité de Lille (CIIL), Lille, 59019, Nord-Pas-de-Calais, France

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.