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

2021 ◽  
Author(s):  
Guillermo H Jimenez-Aleman ◽  
Victoria Castro ◽  
Addis Longdaitsbehere ◽  
Marta Gutierrez-Rodriguez ◽  
Urtzi Garaigorta ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Protoporphyrin Ix ◽  
Therapeutic Index ◽  
Marchantia Polymorpha ◽  
Cancer Therapies ◽  
Potential Candidate ◽  
Pheophorbide A ◽  
Viral Pathogens ◽  
Chlorophyll Derivative ◽  
Chlorophyll Catabolite

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.

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

2021 ◽  
Vol 14 (10) ◽  
pp. 1048
Author(s):  
Guillermo H. Jimenez-Aleman ◽  
Victoria Castro ◽  
Addis Longdaitsbehere ◽  
Marta Gutierrez-Rodríguez ◽  
Urtzi Garaigorta ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Protoporphyrin Ix ◽  
Therapeutic Index ◽  
Marchantia Polymorpha ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Pheophorbide A ◽  
Viral Pathogens ◽  
Chlorophyll Derivative ◽  
Chlorophyll Catabolite

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.

Nanoparticle-based Drug Delivery Systems for Targeted Epigenetics Cancer Therapy

2020 ◽  
Vol 21 (11) ◽  
pp. 1084-1098
Author(s):  
Fengqian Chen ◽  
Yunzhen Shi ◽  
Jinming Zhang ◽  
Qi Liu
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Cancer Therapy ◽  
Drug Delivery Systems ◽  
Therapeutic Index ◽  
Delivery Systems ◽  
Epigenetic Therapy ◽  
Cancer Therapies ◽  
Therapeutic Benefits ◽  
High Therapeutic Index

This review summarizes the epigenetic mechanisms of deoxyribonucleic acid (DNA) methylation, histone modifications in cancer and the epigenetic modifications in cancer therapy. Due to their undesired side effects, the use of epigenetic drugs as chemo-drugs in cancer therapies is limited. The drug delivery system opens a door for minimizing these side effects and achieving greater therapeutic benefits. The limitations of current epigenetic therapies in clinical cancer treatment and the advantages of using drug delivery systems for epigenetic agents are also discussed. Combining drug delivery systems with epigenetic therapy is a promising approach to reaching a high therapeutic index and minimizing the side effects.

scholarly journals Pheophorbide a: State of the Art

Marine Drugs ◽  
2020 ◽  
Vol 18 (5) ◽  
pp. 257 ◽  
Author(s):  
Assunta Saide ◽  
Chiara Lauritano ◽  
Adrianna Ianora
Keyword(s):  
Clinical Trials ◽  
Photodynamic Therapy ◽  
Anticancer Activity ◽  
State Of The Art ◽  
Human Cancer ◽  
Human Cancer Cell ◽  
Pheophorbide A ◽  
Human Cancer Cell Lines ◽  
Chlorophyll Breakdown ◽  
Chlorophyll Derivative

Chlorophyll breakdown products are usually studied for their antioxidant and anti-inflammatory activities. The chlorophyll derivative Pheophorbide a (PPBa) is a photosensitizer that can induce significant anti-proliferative effects in several human cancer cell lines. Cancer is a leading cause of death worldwide, accounting for about 9.6 million deaths, in 2018 alone. Hence, it is crucial to monitor emergent compounds that show significant anticancer activity and advance them into clinical trials. In this review, we analyze the anticancer activity of PPBa with or without photodynamic therapy and also conjugated with or without other chemotherapic drugs, highlighting the capacity of PPBa to overcome multidrug resistance. We also report other activities of PPBa and different pathways that it can activate, showing its possible applications for the treatment of human pathologies.

scholarly journals Photosystem Disorder Could be the Key Cause for the Formation of Albino Leaf Phenotype in Pecan

2020 ◽  
Vol 21 (17) ◽  
pp. 6137
Author(s):  
Ji-Yu Zhang ◽  
Tao Wang ◽  
Zhan-Hui Jia ◽  
Zhong-Ren Guo ◽  
Yong-Zhi Liu ◽  
...  
Keyword(s):  
Chlorophyll A ◽  
Molecular Mechanisms ◽  
Chlorophyll Biosynthesis ◽  
Protoporphyrin Ix ◽  
Photosynthetic Electron Transport ◽  
Chlorophyll Degradation ◽  
Pheophorbide A ◽  
Leaf Phenotype ◽  
Photosynthesis Pathway ◽  
Almost All

Pecan is one of the most famous nut species in the world. The phenotype of mutants with albino leaves was found in the process of seeding pecan, providing ideal material for the study of the molecular mechanisms leading to the chlorina phenotype in plants. Both chlorophyll a and chlorophyll b contents in albino leaves (ALs) were significantly lower than those in green leaves (GLs). A total of 5171 differentially expression genes (DEGs) were identified in the comparison of ALs vs. GLs using high-throughput transcriptome sequencing; 2216 DEGs (42.85%) were upregulated and 2955 DEGs (57.15%) were downregulated. The expressions of genes related to chlorophyll biosynthesis (HEMA1, encoding glutamyl-tRNA reductase; ChlH, encoding Mg-protoporphyrin IX chelatase (Mg-chelatase) H subunit; CRD, encoding Mg-protoporphyrin IX monomethylester cyclase; POR, encoding protochlorophyllide reductase) in ALs were significantly lower than those in GLs. However, the expressions of genes related to chlorophyll degradation (PAO, encoding pheophorbide a oxygenase) in ALs were significantly higher than those in GLs, indicating that disturbance of chlorophyll a biosynthesis and intensification of chlorophyll degradation lead to the absence of chlorophyll in ALs of pecan. A total of 72 DEGs associated with photosynthesis pathway were identified in ALs compared to GLs, including photosystem I (15), photosystem II (19), cytochrome b6-f complex (3), photosynthetic electron transport (6), F-type ATPase (7), and photosynthesis-antenna proteins (22). Moreover, almost all the genes (68) mapped in the photosynthesis pathway showed decreased expression in ALs compared to GLs, declaring that the photosynthetic system embedded within the thylakoid membrane of chloroplast was disturbed in ALs of pecan. This study provides a theoretical basis for elucidating the molecular mechanism underlying the phenotype of chlorina seedlings of pecan.

scholarly journals Synthesis and Evaluation of Anti-Rhinovirus 1B Activity of Oxazolinyl-Isoflavans and -3(2H)-Isoflavenes

1992 ◽  
Vol 3 (4) ◽  
pp. 195-202 ◽  
Author(s):  
N. Desideri ◽  
C. Conti ◽  
I. Sestili ◽  
P. Tomao ◽  
M. L. Stein ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Antiviral Activity ◽  
Cytopathic Effect ◽  
Potent Inhibitor ◽  
Therapeutic Index ◽  
Intermediate Compound ◽  
Plaque Formation ◽  
Interesting Compound ◽  
Viral Cytopathic Effect

Oxazolinyl-isoflavans and −3(2H)-isoflavenes, substituted or not with a chlorine atom, were synthesized in order to compare their anti-rhinovirus activity with that of previously studied analogous compounds. The activity of the oxazolines and of the esters and acids, which are intermediates in the synthesis, was studied in vitro against rhinovirus serotype 1B infection in HeLa cells. The ability of various non cytotoxic concentrations to interfere with the development of the viral cytopathic effect and plaque formation was examined. All the tested compounds exerted a significant antiviral activity, and most of them were as active as some representative compounds of the oxazolinyl-phenoxyalkylisoxazole (WIN) series. 6-Oxazolinylisoflavan (VI) appeared to be the most interesting compound due to its high activity and therapeutic index. Among the substituted isoflavans and isoflavenes tested so far, the intermediate compound 6-chloro-3 (2H)-isoflavene-4′-carboxylic acid (XIX) was unexpectedly the most potent inhibitor of rhinovirus 1B plaque formation.

scholarly journals 2’-Fluoro-2’-deoxycytidine inhibits murine norovirus replication and synergizes MPA, ribavirin and T705

2020 ◽  
Vol 165 (11) ◽  
pp. 2605-2613
Author(s):  
Peifa Yu ◽  
Yining Wang ◽  
Yunlong Li ◽  
Yang Li ◽  
Zhijiang Miao ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Antiviral Treatment ◽  
Antiviral Drug ◽  
Viral Gastroenteritis ◽  
Potential Candidate ◽  
Murine Norovirus ◽  
Health Burden ◽  
Antiviral Effects ◽  
Causative Agents ◽  
Acute Viral Gastroenteritis

AbstractNoroviruses are the main causative agents of acute viral gastroenteritis worldwide. However, no vaccine or specific antiviral treatment is available, imposing a heavy global health burden. The nucleoside analogue 2’-fluoro-2’-deoxycytidine (2’-FdC) has been reported to have broad antiviral activity. Here, we report that 2’-FdC significantly inhibits murine norovirus replication in macrophages. This effect was partially reversed by exogenous supplementation of cytidine triphosphate. The combination of 2’-FdC with mycophenolic acid, ribavirin or favipiravir (T705) exerts synergistic antiviral effects. These results indicate that 2’-FdC is a potential candidate for antiviral drug development against norovirus infection.

Response of Liverwort Cells to Peroxidizing Herbicides

1992 ◽  
Vol 47 (5-6) ◽  
pp. 394-399
Author(s):  
Shuji Iwata ◽  
Naoko Nakayama ◽  
Shunji Nakagawara ◽  
Yoshimoto Ohta ◽  
Takaharu Tanaka ◽  
...  
Keyword(s):  
Cell Growth ◽  
Oxidative Damage ◽  
Early Treatment ◽  
Protoporphyrin Ix ◽  
Cell Suspension Cultures ◽  
Exponential Phase ◽  
Marchantia Polymorpha ◽  
Late Exponential Phase ◽  
Kinetics Of

Cell suspension cultures of the liverwort, Marchantia polymorpha L. were found useful to study the influence of peroxidizing herbicides either on the greening process or on the fully green cells. The cells of both physiological stages exhibit a characteristic sensitivity to the herbicides. The sensitivity increased rapidly during the exponential phase of growth, reached a maximum during the late exponential phase, and then decreased in the stationary phase. We investigated the kinetics of accumulation of protoporphyrin IX (PPIX) in Marchantia cells treated with several peroxidizing herbicides at various stages of cell growth, and observed a correlation between accumulation of PPIX and herbicidal damage. The glutathione (GSH) content in the cell was also investigated to examine the role of GSH against herbicide treatment. In the light, GSH levels in the cells treated with AFM rose rapidly reaching a peak after 8 h, and rapidly decreased subsequently. The beginning of PPIX accumulation coincided with the decline of GSH after 8 h of treatment. Obviously, GSH plays a key role in protection against oxidative damage caused by AFM in the early treatment period. In the dark, AFM also induced an accumulation of GSH and PPIX, followed by a decline in GSH and PPIX contents during a 20 h incubation. The decline of PPIX was observed several hours after GSH starts to decrease, remaining at a constant level for the following 40 h, leading to accumulation of an other fluorescent still-unknown pigment.

scholarly journals ANTIVIRAL ACTIVITY OF THE MELANIN FROM BIRCH FUNGUS (INONOTUS OBLIQUUS) OBTAINED BY CUL-TIVATING F-1244 STRAIN ISOLATING TO PURE CULTURE

2020 ◽  
pp. 283-289
Author(s):  
Tat'yana Nikolayevna Ilyicheva ◽  
Grigoriy Grigor'yevich Anan’ko ◽  
Tat'yana Alekseyevna Kosogova ◽  
Sergey Yevgen'yevich Olkin ◽  
Vladimir Vilor'yevich Omigov ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Comparative Study ◽  
Pure Culture ◽  
Submerged Culture ◽  
Therapeutic Index ◽  
Inonotus Obliquus ◽  
Toxic Dose ◽  
Naturally Occurring

The aim of the work was a comparative study of the antiviral activity of the melanin isolated from submerged culture of basidiomycete birch fungus Inonotus obliquus F-1244 and melanin obtained from natural birch fungus. We showed that the melanin isolated from cultivated birch fungus is similar to the melanin from natural birch fungus in respect of its physicochemical and antiviral properties. Although, the sample`s activity depended not only on the source of melanin, but also on the method of isolating and purification. The toxic dose (CD50) varied from 300 to 2500 µg/ml. The effective antiviral dose in the case of A/H1N1pdm09 (ID50) was one from 10 to 47 µg/ml. The highest therapeutic index was for the melanin of the cultivated birch fungus, purified by dialysis. The index made 160; it is higher in 2, 5 times in comparison with natural birch fungus. The melanin from cultivated birch fungus is a promising substance for the developing of naturally occurring medication.

scholarly journals The antiviral activity of the compound chalcone (4-ethoxy-2-hydroxy-4, 6-dimethoxy-chalcone) against rubella virus in vitro

2008 ◽  
Vol 5 (3) ◽  
pp. 391-394 ◽  
Author(s):  
Baghdad Science Journal
Keyword(s):  
Antiviral Activity ◽  
Organ Culture ◽  
Rubella Virus ◽  
Side Effect ◽  
Therapeutic Index ◽  
Maximum Tolerated Dose ◽  
Antiviral Compound ◽  
Tissue And Organ Culture ◽  
Margin Of Safety

The studies on the antiviral compound chalcone in vitro in both tissue and organ culture systems against rubella virus glass that this compound relatively non toxic to the cell culture and organ culture of the concentration of 8 ug/ml or less, chalcone have significantly antiviral activity against rubella virus in tissue culture and organ culture. We find that a concentration of 0.03ug/ml or more inhibit the IOOTCID50 of rubella virus. The therapeutic index (TI) used in this study to evaluate the drug, the (TI) which is the ratio of the dose of drug which is just toxic (Maximum tolerated dose) to the dose which is just effective (Minimum effective dose). If this index is one or less it not possible to use the drug under the conditions outlined without causing side effect, if the index is larger than the margin of safety is accordingly great, the TI of chalcone against rubella virus more than 70, therefore this compound if used in man have no side effect .

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