SARS-CoV-2 Fears Green: The Chlorophyll Catabolite Pheophorbide A Is a Potent Antiviral

SARS-CoV-2 pandemic is having devastating consequences worldwide. Although vaccination advances at good pace, effectiveness against emerging variants is unpredictable. The virus has displayed a remarkable resistance to treatments and no drugs have been proved fully effective against COVID-19. Thus, despite the international efforts, there is still an urgent need for new potent and safe antivirals against SARS-CoV-2. Here, we exploited the enormous potential of plant metabolism using the bryophyte Marchantia polymorpha L. and identified a potent SARS-CoV-2 antiviral, following a bioactivity-guided fractionation and mass-spectrometry approach. We found that the chlorophyll derivative Pheophorbide a (PheoA), a porphyrin compound similar to animal Protoporphyrin IX, has an extraordinary antiviral activity against SARS-CoV-2, preventing infection of cultured monkey and human cells, without noticeable cytotoxicity. We also show that PheoA targets the viral particle, interfering with its infectivity in a dose- and time-dependent manner. Besides SARS-CoV-2, PheoA also displayed a broad-spectrum antiviral activity against enveloped RNA viral pathogens such as HCV, West Nile, and other coronaviruses. Our results indicate that PheoA displays a remarkable potency and a satisfactory therapeutic index, which together with its previous use in photoactivable cancer therapy in humans, suggest that it may be considered as a potential candidate for antiviral therapy against SARS-CoV-2.

SARS-CoV-2 fears green: the chlorophyll catabolite Pheophorbide a is a potent antiviral

The SARS-CoV-2 pandemic is having devastating consequences worldwide. Although vaccination advances at good pace, effectiveness against emerging variants of the virus is unpredictable. The virus has displayed a remarkable resistance to treatments and no drugs have been proved fully effective against Covid-19. Thus, despite the international efforts, there is still an urgent need for new potent and safe antivirals against SARS-CoV-2. Here we exploited the enormous potential of plant metabolism, in particular the bryophyte Marchantia polymorpha, and following a bioactivity-guided fractionation and mass-spectrometry approach, identified a potent SARS-CoV-2 antiviral. We found that the chlorophyll derivative Pheophorbide a (PheoA), a natural porphyrin similar to animal Protoporphyrin IX, has an extraordinary antiviral activity against SARS-CoV-2 preventing infection of cultured monkey and human cells, without noticeable citotoxicity. We also show that PheoA prevents coronavirus entry into the cells by directly targeting the viral particle. Besides SARS-CoV-2, PheoA also displayed a broad-spectrum antiviral activity against (+)strand RNA viral pathogens such as HCV, West Nile, and other coronaviruses, but not against (-)strand RNA viruses, such as VSV. 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. Moreover, PheoA adds to remdesivir's efficiency and is currently employed in photoactivable cancer therapies in humans.

Chlorophyll derivative activated with sunlight for malaria vector control: a small-scale field study

Background Malaria is a life-threatening infectious disease transmitted through the bite of the Anopheles mosquito; hence, it could be prevented by a proper vector control. To date, this could be achieved by controlling adult mosquitoes using synthetic chemicals such as DDT for indoor residual spraying (IRS) and pyrethroid-treated bed nets. These approaches possess potential toxicities; therefore, a new ecologically safe technology for vector control was developed in this study. Methods Small-scale field studies were performed in the swamp with anopheline larvae from different sub-saharan countries, such as Sudan, Uganda and Ethiopia. Photodynamic control of anopheles larvae was employed using a chlorophyll derivative, pheophorbide-a (Ph-a) as a photosensitizer and sunlight as a light source. This could interrupt the life cycle of the Anopheles mosquitoes from the larval stage, which induces the interruption of the malaria disease cycle. Results Ph-a accumulates in the larval body and upon sunlight exposure, it induces oxidative stress, which causes 85 to 100% larval death 24 hours after treatment with Ph-a. This photosensitizer’s effect persisted up to 21 days in the new generations in the same breeding site (residual effect). It is a target selective formula that has shown no effect on the other beneficial organisms in the breeding site. Conclusions This technique was found to be both effective and highly selective. It achieved a high mortality rate of mosquito larvae, while maintaining the highest levels of human safety and environmental friendliness.

Effects of Ethanol Extracts from Grateloupia elliptica, a Red Seaweed, and Its Chlorophyll Derivative on 3T3-L1 Adipocytes: Suppression of Lipid Accumulation through Downregulation of Adipogenic Protein Expression

Grateloupia elliptica (G. elliptica) is a red seaweed with antioxidant, antidiabetic, anticancer, anti-inflammatory, and anticoagulant activities. However, the anti-obesity activity of G. elliptica has not been fully investigated. Therefore, the effect of G. elliptica ethanol extract on the suppression of intracellular lipid accumulation in 3T3-L1 cells by Oil Red O staining (ORO) was evaluated. Among the eight red seaweeds tested, G. elliptica 60% ethanol extract (GEE) exhibited the highest inhibition of lipid accumulation. GEE was the only extract to successfully suppress lipid accumulation among ethanol extracts from eight red seaweeds. In this study, we successfully isolated chlorophyll derivative (CD) from the ethyl acetate fraction (EA) of GEE by high-performance liquid chromatography and evaluated their inhibitory effect on intracellular lipid accumulation in 3T3-L1 adipocytes. CD significantly suppressed intracellular lipid accumulation. In addition, CD suppressed adipogenic protein expression such as sterol regulatory element-binding protein-1 (SREBP-1), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-α (C/EBP-α), and fatty acid binding protein 4 (FABP4). Taken together, our results indicate that CD from GEE inhibits lipid accumulation by suppressing adipogenesis via the downregulation of adipogenic protein expressions in the differentiated adipocytes. Therefore, chlorophyll from G. elliptica has a beneficial effect on lipid metabolism and it could be utilized as a potential therapeutic agent for preventing obesity.

Developments in Vascular-Targeted Photodynamic Therapy for Urologic Malignancies

With improved understanding of cancer biology and technical advancements in non-invasive management of urological malignancies, there is renewed interest in photodynamic therapy (PDT) as a means of focal cancer treatment. The application of PDT has also broadened as a result of development of better-tolerated and more effective photosensitizers. Vascular-targeted PDT (VTP) using padeliporfin, which is a water-soluble chlorophyll derivative, allows for tumor-specific cytotoxicity and has demonstrated efficacy in the management of urologic malignancies. Herein, we describe the evolution of photodynamic therapy in urologic oncology and the role of VTP in emerging treatment paradigms.