4.6 Article

Inactivation of Dengue and Yellow Fever viruses by heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX

Journal

JOURNAL OF APPLIED MICROBIOLOGY
Volume 120, Issue 3, Pages 790-804

Publisher

WILEY
DOI: 10.1111/jam.13038

Keywords

antiviral; Dengue Virus; inactivation; metalloporphyrins; Yellow Fever Virus

Ask authors/readers for more resources

AimsTo investigate the effect of heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX (CoPPIX and SnPPIX), macrocyclic structures composed by a tetrapyrrole ring with a central metallic ion, on Dengue Virus (DENV) and Yellow Fever Virus (YFV) infection. Methods and ResultsTreatment of HepG2 cells with heme, CoPPIX and SnPPIX after DENV infection reduced infectious particles without affecting viral RNA contents in infected cells. The reduction of viral load occurs only with the direct contact of DENV with porphyrins, suggesting a direct effect on viral particles. Previously incubation of DENV and YFV with heme, CoPPIX and SnPPIX resulted in viral particles inactivation in a dose-dependent manner. Biliverdin, a noncyclical porphyrin, was unable to inactivate the viruses tested. Infection of HepG2 cells with porphyrin-pretreated DENV2 results in a reduced or abolished viral protein synthesis, RNA replication and cell death. Treatment of HepG2 or THP-1 cell lineage with heme or CoPPIX after DENV infection with a very low MOI resulted in a decreased DENV replication and protection from death. ConclusionsHeme, CoPPIX and SnPPIX possess a marked ability to inactivate DENV and YFV, impairing its ability to infect and induce cytopathic effects on target cells. Significance and Impact of the StudyThese results open the possibility of therapeutic application of porphyrins or their use as models to design new antiviral drugs against DENV and YFV.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Immunology

Common Dysregulation of Innate Immunity Pathways in Human Primary Astrocytes Infected With Chikungunya, Mayaro, Oropouche, and Zika Viruses

Victor Emmanuel Viana Geddes, Otavio Jose Bernardes Brustolini, Liliane Tavares de Faria Cavalcante, Filipe Romero Rebello Moreira, Fernando Luz de Castro, Ana Paula de Campos Guimaraes, Alexandra Lehmkuhl Gerber, Camila Menezes Figueiredo, Luan Pereira Diniz, Eurico de Arruda Neto, Amilcar Tanuri, Renan Pedra Souza, Iranaia Assuncao-Miranda, Soniza Vieira Alves-Leon, Luciana Ferreira Romao, Jorge Paes Barreto Marcondes de Souza, Ana Tereza Ribeiro de Vasconcelos, Renato Santana de Aguiar

Summary: Arboviruses pose a major threat worldwide, particularly in tropical countries. Astrocytes play a crucial role in controlling inflammation, extracellular matrix, and glutamate neurotoxicity in the central nervous system. Infection with different arboviruses results in differential gene expression and pathway changes, with common down-regulation of immune and antiviral responses.

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2021)

Article Biochemistry & Molecular Biology

Searching for drug leads targeted to the hydrophobic cleft of dengue virus capsid protein

Liliane O. Ortlieb, Icaro P. Caruso, Nathane C. Mebus-Antunes, Andrea T. Da Poian, Elaine da C. Petronilho, Jose Daniel Figueroa-Villar, Claudia J. Nascimento, Fabio C. L. Almeida

Summary: A study synthesised and screened 18 aromatic derivatives of guanylhydrazones and oximes aromatic for their ability to bind to dengue virus capsid protein. Results showed that five compounds were able to bind to a specific region of the capsid protein, inhibiting the virus infectivity.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2022)

Article Immunology

Infection of Endothelial Cells by Dengue Virus Induces ROS Production by Different Sources Affecting Virus Replication, Cellular Activation, Death and Vascular Permeability

Lana Monteiro Meuren, Elisa Beatriz Prestes, Michelle Premazzi Papa, Luiza Rachel Pinheiro de Carvalho, Yasmin Mucuna Mustafa, Leandro Silva da Costa, Andrea T. Da Poian, Marcelo Torres Bozza, Luciana Barros Arruda

Summary: Infection with DENV induces ROS production in HBMECs through activation of mitochondrial function and NADPH oxidase, impacting cell physiology and leading to increased cell death and endothelial permeability. Inhibiting ROS generation by targeting mitochondrial or NOX pathways can reduce virus replication, cell death, and inflammation, presenting potential therapeutic targets for preventing dengue pathogenesis.

FRONTIERS IN IMMUNOLOGY (2022)

Article Biochemistry & Molecular Biology

Insights into the specificity for the interaction of the promiscuous SARS-CoV-2 nucleocapsid protein N-terminal domain with deoxyribonucleic acids

Icaro Putinhon Caruso, Vitor dos Santos Almeida, Mariana Juliani do Amaral, Guilherme Caldas de Andrade, Gabriela Rocha de Araujo, Talita Stelling de Araujo, Jessica Moreira de Azevedo, Glauce Moreno Barbosa, Leonardo Bartkevihi, Peter Reis Bezerra, Katia Maria dos Santos Cabral, Isabella Otenio de Lourenco, Clara L. F. Malizia-Motta, Aline de Luna Marques, Nathane Cunha Mebus-Antunes, Thais Cristtina Neves-Martins, Jessica Marostica de Sa, Karoline Sanches, Marcos Caique Santana-Silva, Ariana Azevedo Vasconcelos, Marcius da Silva Almeida, Gisele Cardoso de Amorim, Cristiane Dinis Anobom, Andrea T. Da Poian, Francisco Gomes-Neto, Anderson S. Pinheiro, Fabio C. L. Almeida

Summary: This study investigates the binding characteristics of the SARS-CoV-2 nucleocapsid protein with nucleic acid sequences and reveals its role in RNA transcription and liquid-liquid phase separation. The findings suggest that the binding of the nucleocapsid protein to a specific sequence can induce DNA melting, which is crucial for viral infection. Additionally, the study shows a preference for the nucleocapsid protein to form liquid condensates with specific sequences, providing insights for the design of drugs targeting the nucleocapsid protein.

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES (2022)

Article Multidisciplinary Sciences

The interaction of dengue virus capsid protein with negatively charged interfaces drives the in vitro assembly of nucleocapsid-like particles

Nathane C. Mebus-Antunes, Wellington S. Ferreira, Glauce M. Barbosa, Thais C. Neves-Martins, Gilberto Weissmuller, Fabio C. L. Almeida, Andrea T. Da Poian

Summary: This study establishes the conditions for in vitro assembly of DENV nucleocapsid-like particles (NCLPs) using recombinant DENVC. The assembly process is concentration-dependent and involves DENVC charge neutralization. The results shed light on the assembly mechanism of DENV and have important implications for understanding the virus.

PLOS ONE (2022)

Article Pharmacology & Pharmacy

Targeting Zika Virus with New Brain- and Placenta-Crossing Peptide-Porphyrin Conjugates

Toni Todorovski, Diogo A. Mendonca, Lorena O. Fernandes-Siqueira, Christine Cruz-Oliveira, Giuseppina Guida, Javier Valle, Marco Cavaco, Fernanda I. Limas, Vera Neves, Iris Cadima-Couto, Sira Defaus, Ana Salome Veiga, Andrea T. Da Poian, Miguel A. R. B. Castanho, David Andreu

Summary: Viral disease outbreaks pose a serious threat to global health, particularly the Zika virus, which can cause severe complications during pregnancy. There is currently no effective treatment, but peptide-porphyrin conjugation shows promise as a strategy for filling this treatment gap.

PHARMACEUTICS (2022)

Article Multidisciplinary Sciences

On the caveats of a multiplex test for SARS-CoV-2 to detect seroconversion after infection or vaccination

Lorena O. Fernandes-Siqueira, Fabiana A. P. Ferreira, Bruna G. Sousa, Nathane C. Mebus-Antunes, Thais C. Neves-Martins, Fabio C. L. Almeida, Gustavo C. Ferreira, Didier Salmon, Luciana S. Wermelinger, Andrea T. Da Poian

Summary: This study optimized an enzyme-linked immunosorbent assay (ELISA) test for detecting antibodies against various proteins of SARS-CoV-2. The test was applied to a cohort of individuals and showed potential for customization and valuable applications in understanding immune responses and vaccine coverage.

SCIENTIFIC REPORTS (2022)

Article Chemistry, Multidisciplinary

Comprehensive Fragment Screening of the SARS-CoV-2 Proteome Explores Novel Chemical Space for Drug Development

Hannes Berg, Maria A. Wirtz Martin, Nadide Altincekic, Islam Alshamleh, Jasleen Kaur Bains, Julius Blechar, Betul Ceylan, Vanessa de Jesus, Karthikeyan Dhamotharan, Christin Fuks, Santosh L. Gande, Bruno Hargittay, Katharina F. Hohmann, Marie T. Hutchison, Sophie Marianne Korn, Robin Krishnathas, Felicitas Kutz, Verena Linhard, Tobias Matzel, Nathalie Meiser, Anna Niesteruk, Dennis J. Pyper, Linda Schulte, Sven Trucks, Kamal Azzaoui, Marcel J. J. Blommers, Yojana Gadiya, Reagon Karki, Andrea Zaliani, Philip Gribbon, Marcius da Silva Almeida, Cristiane Dinis Anobom, Anna L. Bula, Matthias Butikofer, Icaro Putinhon Caruso, Isabella Caterina Felli, Andrea T. Da Poian, Gisele Cardoso de Amorim, Nikolaos K. Fourkiotis, Angelo Gallo, Dhiman Ghosh, Francisco Gomes-Neto, Oksana Gorbatyuk, Bing Hao, Vilius Kurauskas, Lauriane Lecoq, Yunfeng Li, Nathane Cunha Mebus-Antunes, Miguel Mompean, Thais Cristtina Neves-Martins, Marti Ninot-Pedrosa, Anderson S. Pinheiro, Letizia Pontoriero, Yulia Pustovalova, Roland Riek, Angus J. Robertson, Marie Jose Abi Saad, Miguel A. Trevino, Aikaterini C. Tsika, Fabio C. L. Almeida, Ad Bax, Katherine Henzler-Wildman, Jeffrey C. Hoch, Kristaps Jaudzems, Douglas Laurents, Julien Orts, Roberta Pierattelli, Georgios A. Spyroulias, Elke Duchardt-Ferner, Jan Ferner, Boris Furtig, Martin Hengesbach, Frank Lohr, Nusrat Qureshi, Christian Richter, Krishna Saxena, Andreas Schlundt, Sridhar Sreeramulu, Anna Wacker, Julia E. Weigand, Julia Wirmer-Bartoschek, Jens Wohnert, Harald Schwalbe

Summary: This study explores novel drug design against SARS-CoV-2 through NMR screening and computational mapping. They identified multiple molecules that bind to SARS-CoV-2 proteins and studied their structural and chemical properties, providing new insights for drug development.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2022)

Article Biophysics

The 1H, 15N and 13C resonance assignments of dengue virus capsid protein with the deletion of the intrinsically disordered N-terminal region

Glauce M. Barbosa, Maria A. Morando, Andrea T. Da Poian, Fabio C. L. Almeida

Summary: Dengue virus, an enveloped virus belonging to the Flaviviridae family, is responsible for an endemic arboviral disease in humans. The capsid protein of Dengue virus forms homodimers in solution, consisting of 4 alpha-helices and an intrinsically disordered N-terminal region. The N-terminal region is involved in binding membranous structures in host cells and nucleotide recognition.

BIOMOLECULAR NMR ASSIGNMENTS (2023)

Article Cell Biology

SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome in mice

Fabricia L. Fontes-Dantas, Gabriel G. Fernandes, Elisa G. Gutman, Emanuelle V. De Lima, Leticia S. Antonio, Mariana B. Hammerle, Hannah P. Mota-Araujo, Lilian C. Colodeti, Suzana M. B. Araujo, Gabrielle M. Froz, Talita N. da Silva, Larissa A. Duarte, Andreza L. Salvio, Karina L. Pires, Luciane A. A. Leon, Claudia Cristina F. Vasconcelos, Luciana Romao, Luiz Eduardo B. Savio, Jerson L. Silva, Robson da Costa, Julia R. Clarke, Andrea T. Da Poian, Soniza V. Alves-Leon, Giselle F. Passos, Claudia P. Figueiredo

Summary: Cognitive dysfunction in post-COVID-19 syndrome may be caused by the release of SARS-CoV-2 Spike protein, which can lead to neuroinflammation, synapse elimination, and memory dysfunction mediated by Toll-like receptor 4 (TLR4) signaling. Infusing Spike protein into the brains of mice reproduced cognitive impairment similar to post-COVID-19 syndrome. In a group of 86 mild COVID-19 patients, a specific TLR4 genotype was associated with poor cognitive outcome. These findings highlight TLR4 as a key target for investigating long-term cognitive dysfunction after COVID-19 infection.

CELL REPORTS (2023)

Article Multidisciplinary Sciences

Self-assembly of dengue virus empty capsid-like particles in solution

Thais C. Neves-Martins, Nathane C. Mebus-Antunes, Carlos H. G. Neto, Glauce M. Barbosa, Fabio C. L. Almeida, Icaro P. Caruso, Andrea T. Da Poian

Summary: The researchers designed a mutant of the dengue virus capsid protein (DENVC) by replacing a positively charged spot with a cysteine residue, resulting in the self-assembly of capsid-like particles (CLP) in solution without nucleic acids.

ISCIENCE (2023)

Article Behavioral Sciences

Different outcomes of neonatal and adult Zika virus infection on startle reflex and prepulse inhibition in mice

Isis N. O. Souza, Brenda S. Andrade, Paula S. Frost, Romulo L. S. Neris, Daniel Gavino-Leopoldino, Andrea T. Da Poian, Iranaia Assuncao-Miranda, Claudia P. Figueiredo, Julia R. Clarke, Gilda A. Neves

Summary: In this study, different outcomes were observed in mice infected with Zika virus (ZIKV) based on age and sex: neonatally infected animals showed an increase in prepulse inhibition (PPI) and delayed startle latency, while adult-infected male mice had lower startle amplitude and both sexes showed PPI impairment 14 days after infection. These findings contribute to a better understanding of the functional impacts of ZIKV on the nervous system and provide insight into the behavioral and cognitive alterations caused by the virus. The study supports the use of startle reflex testing in ZIKV-exposed patients, especially infants, for early detection of functional neuromotor damage and early intervention.

BEHAVIOURAL BRAIN RESEARCH (2023)

Article Biochemistry & Molecular Biology

Integrated NMR and MS Analysis of the Plasma Metabolome Reveals Major Changes in One-Carbon, Lipid, and Amino Acid Metabolism in Severe and Fatal Cases of COVID-19

Marcos C. C. Gama-Almeida, Gabriela D. A. Pinto, Livia Teixeira, Eugenio D. D. Hottz, Paula Ivens, Hygor Ribeiro, Rafael Garrett, Alexandre G. G. Torres, Talita I. A. Carneiro, Bianca de O. Barbalho, Christian Ludwig, Claudio J. J. Struchiner, Iranaia Assuncao-Miranda, Ana Paula C. Valente, Fernando A. A. Bozza, Patricia T. Bozza, Gilson C. C. dos Santos Jr, Tatiana El-Bacha

Summary: Brazil has the second-highest COVID-19 death rate worldwide, with Rio de Janeiro being one of the states with the highest rate in the country. Despite vaccine coverage, COVID-19 is expected to become an endemic disease. The molecular mechanisms underlying the progression of the disease and the development of long COVID-19 are still not fully understood.

METABOLITES (2023)

Article Infectious Diseases

IgA quantification as a good predictor of the neutralizing antibodies levels after vaccination SARS-CoV-2

Lorena O. Fernandes-Siqueira, Bruna G. Sousa, Carlos E. Cleto, Luciana S. Wermelinger, Beatriz L. L. Caetano, Agatha R. Pacheco, Simone M. Costa, Fabio C. L. Almeida, Gustavo C. Ferreira, Didier Salmon, Ada M. B. Alves, Andrea T. Da Poian

Summary: This study aimed to evaluate the correlation between serum antibody seroconversion and neutralizing antibody titers in individuals who received a complete initial vaccination schedule. The results showed that although IgG titers were high in all individuals after vaccination, the amounts of neutralizing antibodies varied among the groups. Serum neutralizing antibody concentrations were more comparable to IgA levels, suggesting that these antibodies have a major neutralizing capacity against SARS-CoV-2.

JOURNAL OF CLINICAL VIROLOGY PLUS (2022)

No Data Available