Using a bioactivity-guided chromatographic approach, in addition to mass-spectrometry (MS), Guillermo H. Jimenez-Aleman and colleagues identified the antiviral metabolite as Pheophorbide a (PheoA), a porphyrin chlorophyll derivative very similar to animal antiviral metabolite Protoporphyrin IX, in the bryophyte Marchantia polymorpha. Their study recently appeared in BioRxiv.
To confirm the antiviral potential of PheoA, a commercially available PheoA stock solution was serially diluted and mixed with a virus stock to inoculate Vero E6 and Huh7-ACE2 cells (human hepatoma cells expressing ACE2). They found that PheoA has an extraordinary antiviral activity against SARS-CoV-2 preventing infection of cultured monkey and human cells, without noticeable citotoxicity. Additionally, it has been shown that, PheoA prevents coronavirus entry into the cells by directly targeting the viral particle.
They also determined the antiviral spectrum of PheoA on different enveloped and non-enveloped viruses. They showed that, besides SARS-CoV-2, PheoA also displayed a broad-spectrum antiviral activity against enveloped (+)strand RNA viral pathogens such as HCV, West Nile, and other coronaviruses, but not against (-)strand RNA viruses, such as VSV.
Finally, they determined whether the addition of PheoA to remdesivir treatment could result in a synergistic effect on viral infection. They showed that increasing concentrations of PheoA (upto 40nM) improved remdesivir efficacy and viceversa.
“Our results indicate that PheoA displays a remarkable potency and a satisfactory therapeutic index, and suggest that it may be considered as a potential candidate for antiviral therapy against SARS-CoV-2.”— they concluded.
Featured image: Scheme of Pheophobide a preparation from plant material. KG, Silica gel 60. AcOEt, ethyl acetate. MeOH, methanol. © Guillermo H. Jimenez-Aleman et al.
Reference: Guillermo H Jimenez-Aleman, Victoria Castro, Addis Longdaitsbehere, Marta Gutierrez-Rodriguez, Urtzi Garaigorta, Pablo Gastaminza, Roberto Solano, “SARS-CoV-2 fears green: the chlorophyll catabolite Pheophorbide a is a potent antiviral”, bioRxiv 2021.07.31.454592; doi: https://doi.org/10.1101/2021.07.31.454592
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