RT Journal Article SR Electronic T1 A photoactivable natural product with broad antiviral activity against enveloped viruses including highly pathogenic coronaviruses JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.07.09.451770 DO 10.1101/2021.07.09.451770 A1 Thomas Meunier A1 Lowiese Desmarets A1 Simon Bordage A1 Moussa Bamba A1 Kévin Hervouet A1 Yves Rouillé A1 Nathan François A1 Marion Decossas A1 Fézan Honora Tra Bi A1 Olivier Lambert A1 Jean Dubuisson A1 Sandrine Belouzard A1 Sevser Sahpaz A1 Karin Séron YR 2021 UL http://biorxiv.org/content/early/2021/07/09/2021.07.09.451770.abstract AB The SARS-CoV-2 outbreak has highlighted the need for broad-spectrum antivirals against coronaviruses (CoVs). Here, pheophorbide a (Pba) was identified as a highly active antiviral molecule against HCoV-229E after bioguided fractionation of plant extracts. The antiviral activity of Pba was subsequently shown for SARS-CoV-2 and MERS-CoV, and its mechanism of action was further assessed, showing that Pba is an inhibitor of coronavirus entry by directly targeting the viral particle. Interestingly, the antiviral activity of Pba depends on light exposure, and Pba was shown to inhibit virus-cell fusion by stiffening the viral membrane as demonstrated by cryo-electron microscopy. Moreover, Pba was shown to be broadly active against several other enveloped viruses, and reduced SARS-CoV-2 and MERS-CoV replication in primary human bronchial epithelial cells. Pba is the first described natural antiviral against SARS-CoV-2 with direct photosensitive virucidal activity that holds potential for COVID-19 therapy or disinfection of SARS-CoV-2 contaminated surfaces.Competing Interest StatementThe authors have declared no competing interest.