A photoactivable natural product with broad antiviral activity against enveloped viruses including highly pathogenic coronaviruses

Thomas Meunier (1, 2) , Lowiese Desmarets (1, 2) , Simon Bordage (3, 4, 5) , Moussa Bamba (3, 4, 6) , Kévin Hervouet (1, 2) , Yves Rouillé (1, 2) , Nathan François (1, 2) , Marion Decossas (7, 8) , Valentin Sencio (1, 2) , François Trottein (1, 2) , Fézan Honora Tra Bi (6) , Olivier Lambert (7, 8) , Jean Dubuisson (1, 2) , Sandrine Belouzard (1, 2) , Sevser Sahpaz (3, 4, 5) , Karin Séron (1, 2)

1 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
2 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
3 Université de Liège
4 JUNIA - JUNIA
5 BioEcoAgro - Equipe 5 - Specialized Metabolites of Plant Origin
6 UNA - Université Nangui Abrogoua
7 CBMN - Chimie et Biologie des Membranes et des Nanoobjets
8 Bordeaux INP - Institut Polytechnique de Bordeaux

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.

Domaines: Sciences du Vivant [q-bio]

Thomas Meunier, Lowiese Desmarets, Simon Bordage, Moussa Bamba, Kévin Hervouet, et al.. A photoactivable natural product with broad antiviral activity against enveloped viruses including highly pathogenic coronaviruses. Antimicrobial Agents and Chemotherapy, 2022, ⟨10.1128/AAC.01581-21⟩. ⟨hal-03447751⟩