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.

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 Gallium maltolate has in vitro antiviral activity against SARS-CoV-2 and is a potential treatment for COVID-19

2020 ◽  
Vol 28 ◽  
pp. 204020662098378
Author(s):  
Lawrence R Bernstein ◽  
Leike Zhang
Keyword(s):  
Antiviral Activity ◽  
Influenza A ◽  
Colorimetric Assay ◽  
Inflammatory Activity ◽  
Cell Counting ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Influenza A H1n1 ◽  
Anti Inflammatory

Background Gallium has demonstrated strong anti-inflammatory activity in numerous animal studies, and has also demonstrated direct antiviral activity against the influenza A H1N1 virus and the human immunodeficiency virus (HIV). Gallium maltolate (GaM), a small metal-organic coordination complex, has been tested in several Phase 1 clinical trials, in which no dose-limiting or other serious toxicity was reported, even at high daily oral doses for several months at a time. For these reasons, GaM may be considered a potential candidate to treat coronavirus disease 2019 (COVID-19), which is caused by the SARS-CoV-2 virus and can result in severe, sometimes lethal, inflammatory reactions. In this study, we assessed the ability of GaM to inhibit the replication of SARS-CoV-2 in a culture of Vero E6 cells. Methods The efficacy of GaM in inhibiting the replication of SARS-CoV-2 was determined in a screening assay using cultured Vero E6 cells. The cytotoxicity of GaM in uninfected cells was determined using the Cell Counting Kit-8 (CCK-8) colorimetric assay. Results The results showed that GaM inhibits viral replication in a dose-dependent manner, with the concentration that inhibits replication by 50% (EC50) being about 14 µM. No cytotoxicity was observed at concentrations up to at least 200 µM. Conclusion The in vitro activity of GaM against SARS-CoV-2, together with GaM’s known anti-inflammatory activity, provide justification for testing GaM in COVID-19 patients.

Paeonol Inhibits Prostate Cancer Cell Invasion and Epithelial-Mesenchymal Transformation by Inactivation of STAT3 Pathway

2020 ◽  
Vol 19 (1) ◽  
pp. 15-20
Author(s):  
Junyi Xiang ◽  
Feng Huang ◽  
Renhua Huang ◽  
Jingzhan Su ◽  
Yulong Liu
Keyword(s):  
Prostate Cancer ◽  
Treatment Options ◽  
Surrogate Marker ◽  
Cytotoxic Agents ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Ablation Therapy ◽  
Androgen Ablation ◽  
Mesenchymal Transformation ◽  
Dose Dependent

Prostate cancer is one of the leading causes of death in men all over the world. Treatment options such as androgen ablation therapy and cytotoxic agents have many undesirable side effects, narrow therapeutic windows, or other limitations. In this research, we have explored the effects of paeonol on prostate cancer and its mechanism of action. Our results have shown that paeonol reduced the viability of prostate cancer cells in a dose-dependent manner. The wound-healing assay, a surrogate marker of tumor metastasis, showed that the relative wound width of 10 µM group was less than that of 50 µM paeonol-treated cells. Besides, the results of the transwell assay also showed that the number of migrated cells was significantly lower after treatment with 50 µM paeonol compared to the 10 µM group. The Western blot results showed that paeonol treatment induced a decrease in the mesenchymal markers (vimentin and N-cadherin), while the epithelial marker (E-cadherin) increased in a dose-dependent manner suggesting that paeonol effectively inhibits the epithelial-mesenchymal transformation in PC3 cells. Furthermore, the expression of STAT3 and p-STAT3 was also decreased after paeonol treatment, which indicated that the STAT3 signaling pathway was inhibited by paeonol. To conclude, the results summarized in this paper suggest that paeonol could be a potential candidate in the treatment of prostate cancer.

scholarly journals Synthesis and Evaluation of the Antitumor Activity of Novel 1-(4-Substituted phenyl)-2-ethyl Imidazole Apoptosis Inducers In Vitro

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4293
Author(s):  
Zhen-Wang Li ◽  
Chun-Yan Zhong ◽  
Xiao-Ran Wang ◽  
Shi-Nian Li ◽  
Chun-Yuan Pan ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Cells ◽  
Antiproliferative Activity ◽  
Antitumor Agent ◽  
Positive Control ◽  
Selectivity Index ◽  
Time Dependent ◽  
Potential Candidate ◽  
Dependent Manner

Novel imidazole derivatives were designed, prepared, and evaluated in vitro for antitumor activity. The majority of the tested derivatives showed improved antiproliferative activity compared to the positive control drugs 5-FU and MTX. Among them, compound 4f exhibited outstanding antiproliferative activity against three cancer cell lines and was considerably more potent than both 5-FU and MTX. In particular, the selectivity index indicated that the tolerance of normal L-02 cells to 4f was 23–46-fold higher than that of tumor cells. This selectivity was significantly higher than that exhibited by the positive control drugs. Furthermore, compound 4f induced cell apoptosis by increasing the protein expression levels of Bax and decreasing those of Bcl-2 in a time-dependent manner. Therefore, 4f could be a potential candidate for the development of a novel antitumor agent.

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 Hesperidin Induces Mitochondria Mediated Intrinsic Apoptosis in HPV-positive Cervical Cancer Cells via Regulation of E6/p53 Expression

2020 ◽  
Author(s):  
Fang Ren ◽  
Gong Zhang ◽  
Caiyu Li ◽  
Gailing Li ◽  
Yuan Cao ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Protein Level ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
P53 Expression ◽  
Cervical Cancer Cells ◽  
Apoptotic Proteins

Abstract Background: Hesperetin, an active compound found in citrus fruits, possesses antiproliferative effects toward several types of cancer cell lines, including cervical cancer. In this study, we explore the antitumor effects of Hesperetin on the human cervical cancer human papilloma virus (HPV)-positive (CaSki and HeLa) and HPV-negative (C-33A) cell lines and further elucidated the underlying mechanisms of this action. Methods: Cell viability and proliferation was measured by the MTT assay and 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay, respectively. dUTP-fluorescein nick end-labeling (TUNEL) staining, Annexin V‑fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining and flow cytometry was used to assess the degree of apoptosis. JC-1 staining assay was used to evaluate the change of mitochondrial membrane potential (ΔΨm) and Western blot assays were used to determine apoptosis-related factors at protein level. Results: Hesperetin (100, 200 and 400 μM) exhibited a significant exclusive inhibitory effect against the growth of HPV-infected CaSki and HeLa cancer cells via induction of apoptosis in a concentration-dependent manner, while it was almost not active in HPV-negative C-33A cancer cells and normal cervix epithelial H8 cells. Moreover, this antitumor effect executed by Hesperetin was associated with disruption of ΔΨm, the release of cytochrome c from mitochondria, activation of pro-apoptotic proteins (Bax, cleaved caspase-3 and caspase-9) and inhibition of anti-apoptotic proteins (Bcl-2). During this process, cleaved caspase-8 remained unchanged. In addition, Hesperetin led to a downregulation of E6 oncoprotein expression and upregulation of tumor suppressor protein p53 level. Conclusions: Collectively, these results implicated that Hesperetin can induce apoptosis of HPV‑positive cervical cancer cells via a mitochondria-mediated intrinsic signaling pathway, together with the repression of E6 and enhancement of p53 protein level, indicating Hesperetin may be considered as a potential candidate for the development of innovative anti-HPV cervical cancer agents.

scholarly journals Novel Antiviral Characteristics of Nanosized Copper(I) Iodide Particles Showing Inactivation Activity against 2009 Pandemic H1N1 Influenza Virus

2011 ◽  
Vol 78 (4) ◽  
pp. 951-955 ◽  
Author(s):  
Yoshie Fujimori ◽  
Tetsuya Sato ◽  
Taishi Hayata ◽  
Tomokazu Nagao ◽  
Mikio Nakayama ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Hydroxyl Radicals ◽  
Influenza A ◽  
Virus Titer ◽  
H1n1 Influenza ◽  
Radical Scavenger ◽  
Dependent Manner ◽  
Pandemic H1n1 ◽  
Titration Assay ◽  
Average Size

ABSTRACTWe investigated the antiviral activity of nanosized copper(I) iodide (CuI) particles having an average size of 160 nm. CuI particles showed aqueous stability and generated hydroxyl radicals, which were probably derived from monovalent copper (Cu+). We confirmed that CuI particles showed antiviral activity against an influenza A virus of swine origin (pandemic [H1N1] 2009) by plaque titration assay. The virus titer decreased in a dose-dependent manner upon incubation with CuI particles, with the 50% effective concentration being approximately 17 μg/ml after exposure for 60 min. SDS-PAGE analysis confirmed the inactivation of the virus due to the degradation of viral proteins such as hemagglutinin and neuraminidase by CuI. Electron spin resonance (ESR) spectroscopy revealed that CuI generates hydroxyl radicals in aqueous solution, and radical production was found to be blocked by the radical scavengerN-acetylcysteine. Taken together, these findings indicate that CuI particles exert antiviral activity by generating hydroxyl radicals. Thus, CuI may be a useful material for protecting against viral attacks and may be suitable for applications such as filters, face masks, protective clothing, and kitchen cloths.

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 Antiviral Activity of Benzoic Acid Derivative NC-5 Against Influenza A Virus and Its Neuraminidase Inhibition

2019 ◽  
Vol 20 (24) ◽  
pp. 6261
Author(s):  
Min Guo ◽  
Jiawei Ni ◽  
Jie Yu ◽  
Jing Jin ◽  
Lingman Ma ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Benzoic Acid ◽  
Influenza A Virus ◽  
Influenza A ◽  
Matrix Protein ◽  
Influenza Viruses ◽  
Drug Candidate ◽  
Dependent Manner ◽  
Drug Resistant

The currently available drugs against influenza A virus primarily target neuraminidase (NA) or the matrix protein 2 (M2) ion channel. The emergence of drug-resistant viruses requires the development of new antiviral chemicals. Our study applied a cell-based approach to evaluate the antiviral activity of a series of newly synthesized benzoic acid derivatives, and 4-(2,2-Bis(hydroxymethyl)-5-oxopyrrolidin-l-yl)-3-(5-cyclohexyl-4H-1,2,4-triazol-3-yl)amino). benzoic acid, termed NC-5, was found to possess antiviral activity. NC-5 inhibited influenza A viruses A/FM/1/47 (H1N1), A/Beijing/32/92 (H3N2) and oseltamivir-resistant mutant A/FM/1/47-H275Y (H1N1-H275Y) in a dose-dependent manner. The 50% effective concentrations (EC50) for H1N1 and H1N1-H275Y were 33.6 μM and 32.8 μM, respectively, which showed that NC-5 had a great advantage over oseltamivir in drug-resistant virus infections. The 50% cytotoxic concentration (CC50) of NC-5 was greater than 640 μM. Orally administered NC-5 protected mice infected with H1N1 and H1N1-H275Y, conferring 80% and 60% survival at 100 mg/kg/d, reducing body weight loss, and alleviating virus-induced lung injury. NC-5 could suppress NP and M1 protein expression levels during the late stages of viral biosynthesis and inhibit NA activity, which may influence virus release. Our study proved that NC-5 has potent anti-influenza activity in vivo and in vitro, meaning that it could be regarded as a promising drug candidate to treat infection with influenza viruses, including oseltamivir-resistant viruses.

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