1,721,043 research outputs found
Antiviral Lipopeptide-Cell Membrane Interaction Is Influenced by PEG Linker Length
Full text linkA set of lipopeptides was recently reported for their broad-spectrum antiviral activity against viruses belonging to the Paramyxoviridae family, including human parainfluenza virus type 3 and Nipah virus. Among them, the peptide with a 24-unit PEG linker connecting it to a cholesterol moiety (VG-PEG24-Chol) was found to be the best membrane fusion inhibitory peptide. Here, we evaluated the interaction of the same set of peptides with biomembrane model systems and isolated human peripheral blood mononuclear cells (PBMC). VG-PEG24-Chol showed the highest insertion rate and it was among the peptides that induced a larger change on the surface pressure of cholesterol rich membranes. This peptide also displayed a high affinity towards PBMC membranes. These data provide new information about the dynamics of peptide-membrane interactions of a specific group of antiviral peptides, known for their potential as multipotent paramyxovirus antivirals.Fil: Augusto, Marcelo T.. Universidade de Lisboa. Instituto de Medicina Molecular; PortugalFil: Hollmann, Axel. Universidade de Lisboa. Instituto de Medicina Molecular; Portugal. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Santiago del Estero. Universidad Nacional de Santiago del Estero. Centro de Investigaciones y Transferencia de Santiago del Estero; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Porotto, Matteo. Columbia University Medical Center; Estados UnidosFil: Moscona, Anne. Columbia University Medical Center; Estados UnidosFil: Santos, Nuno C.. Universidade de Lisboa. Instituto de Medicina Molecular; Portuga
Review of antiviral peptides for use against zoonotic and selected non-zoonotic viruses
Full text linkViruses remain one of the leading causes of animal and human disease. Some animal viral infections spread sporadically to human populations, posing a serious health risk. Particularly the emerging viral zoonotic diseases such as the novel, zoonotic coronavirus represent an actual challenge for the scientific and medical community. Besides human health risks, some animal viral infections, although still not zoonotic, represent important economic loses to the livestock industry. Viral infections pose a genuine concern for which there has been an increasing interest for new antiviral molecules. Among these novel compounds, antiviral peptides have been proposed as promising therapeutic options, not only for the growing body of evidence showing hopeful results but also due to the many adverse effects of chemical-based drugs. Here we review the current progress, key targets and considerations for the development of antiviral peptides (AVPs). The review summarizes the state of the art of the AVPs tested in zoonotic (coronaviruses, Rift Valley fever viruses, Eastern Equine Encephalitis Virus, Dengue and Junín virus) and also non-zoonotic farm animal viruses (avian and cattle viruses). Their molecular target, amino acid sequence and mechanism of action are summarized and reviewed.
Antiviral peptides are currently on the cutting edge since they have been reported to display anti-coronavirus activity. Particularly, the review will discuss the specific mode of action of AVPs that specifically inhibit the fusion of viral and host-cell membranes for SARS-CoV-2, showing in detail some important features of the fusion inhibiting peptides that target the spike protein of these risky viruses.Instituto de VirologíaFil: Hollmann, Axel. Universidad Nacional de Santiago del Estero. Centro de Investigaciones en Biofísica Aplicada y Alimentos (CIBAAL). Laboratorio de Compuestos Bioactivos; ArgentinaFil: Hollmann, Axel. Consejo Nacional de Investigaciones Científicas y Tecnológicas; ArgentinaFil: Hollmann, Axel. Universidad Nacional de Quilmes. Instituto de Microbiología Básica y Aplicada. Laboratorio de Microbiología Molecular; ArgentinaFil: Cardoso, Nancy. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Cardoso, Nancy. Consejo Nacional de Investigaciones Científicas y Tecnológicas; ArgentinaFil: Espeche, Juan C. Universidad Nacional de Santiago del Estero. Centro de Investigaciones en Biofísica Aplicada y Alimentos (CIBAAL). Laboratorio de Compuestos Bioactivos; ArgentinaFil: Espeche, Juan C. Consejo Nacional de Investigaciones Científicas y Tecnológicas; ArgentinaFil: Maffía, Paulo C. Universidad Nacional de Hurlingham. Instituto de Biotecnología; ArgentinaFil: Maffía, Paulo C. Consejo Nacional de Investigaciones Científicas y Tecnológicas; Argentin
Improvement of HIV fusion inhibitor C34 efficacy by membrane anchoring and enhanced exposure infection
No full textObjectives: The aim of the present work was to evaluate the interaction of two new HIV fusion inhibitors HIVP3 [C34-polyethylene glycol (PEG)4-cholesterol] and HIVP4 [(C34-PEG4)2-cholesterol] with membrane model systems and human blood cells in order to clarify where and how the fusion inhibitors locate, allowing us to understand their mechanism of action at the molecular level, and which strategies may be followed to increase efficacy. Methods: Lipid vesicles with defined compositions were used for peptide partition and localization studies, based on the intrinsic fluorescence of HIVP3 and HIVP4. Lipid monolayers were employed in surface pressure studies. Finally, human erythrocytes and peripheral blood mononuclear cells (PBMCs) isolated from blood samples were used in dipole potential assays. Results: Membrane partition, dipole potential and surface pressure assays indicate that the new fusion inhibitors interact preferentially with cholesterol-rich liquid-ordered membranes, mimicking biological membrane microdomains known as lipid rafts. HIVP3 and HIVP4 are able to interact with human erythrocytes and PBMCs to a similar degree as a previously described simpler drug with monomeric C34 and lacking the PEG spacer, C34-cholesterol. However, the pocket-binding domain (PBD) of both HIVP3 and HIVP4 is more exposed to the aqueous environment than in C34-cholesterol. Conclusions: The present data allow us to conclude that more efficient blocking of HIV entry results from the synergism between the membranotropic behaviour and the enhanced exposure of the PBD. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved
Coordination forces between lipid bilayers produced by ferricyanide and Ca2+
No full textAttractive forces usually invoked to take place in membrane-membrane contact in aggregation are hydrogen bonding cross-linkings and hydrophobic interactions between opposing surfaces. However, little is known in relation to the presence of coordination forces in the membrane-membrane interaction. These are understood as those that may be favoured by the formation or the participation of coordination complexes between surface specific groups. In this work, we have analyzed the formation of this type of aggregates between phosphatidylcholine vesicles mediated by a coadsorption of ferricyanide and Ca(2+) ions to the interface. The results obtained by surface potential measures, optical and electronic microscopy, FTIR and (1)H NMR spectroscopies indicate that ferricyanide [Fe(CN)(6)](3-) but not of ferrocyanide [Fe(CN)(6)](4-) can form the complex when Ca(2+) has been adsorbed previously to the membrane surface. In this condition, the anion is likely to act as a bridge between two opposing membranes causing a tight aggregation in which geometry and the polarizability of the ligands to Fe(3+) play a role.Fil: Frías, María de los Ángeles. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Griselda, Contis. Universidad Nacional de Rosario; ArgentinaFil: Hollmann, Axel. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Disalvo, Edgardo Anibal. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
Lipophilicity is a key factor to increase the antiviral activity of HIV neutralizing antibodies
No full textThe HIV broadly neutralizing antibody 2F5 targets the transiently exposed epitope in the membrane proximal external region (MPER) of HIV-1 gp41, by a two-step mechanism involving the viral membrane and this viral glycoprotein. It was recently shown that 2F5 conjugation with a cholesterol moiety outside of the antibody paratope substantially increases its antiviral activity. Additionally, the antiviral activity of D5, a human antibody that binds to the N-terminal heptad repeat (NHR) of gp41 and lacks membrane binding, was boosted by the same cholesterol conjugation. In this work, we evaluated the membrane affinity of both antibodies towards membranes of different compositions, using surface plasmon resonance. A correlation was found between membrane affinity and antiviral activity against HIV-1. We propose that the conjugation of cholesterol to 2F5 or D5 allows a higher degree of antibody pre-concentration at the viral membrane. This way, the antibodies become more available to bind efficiently to the gp41 epitope, blocking viral fusion faster than the unconjugated antibody. These results set up a relevant strategy to improve the rational design of therapeutic antibodies against HIV.Fil: Augusto, Marcelo T.. Universidade de Lisboa; PortugalFil: Hollmann, Axel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidade de Lisboa; PortugalFil: Troise, Fulvia. CEINGE Biotecnologie Avanzate S.C.R.L; ItaliaFil: Veiga, Ana S.. Universidade de Lisboa; PortugalFil: Pessi, Antonello. PeptiPharma; ItaliaFil: Santos, Nuno C.. Universidade de Lisboa; Portuga
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Improvement of viral fusion inhibitor enfuvirtide efficacy by conjugation with membrane anchoring lipids
Full text linkThe human immunodeficiency virus type 1 (HIV-1) is a highly pathogenic and evasive virus, for which no cure has yet been achieved. The majority of the antiretroviral drugs developed over the years against this infection target key enzymes in HIV life cycle, such as reverse transcriptase, integrase and protease. Fusion of viral and host cell membranes is a crucial step in virus infectivity;therefore,the development of viral entry inhibitors has great advantages over conventional drugs, since they prevent the release of the viral content into the host cell. Previous studies showed that the antiviral activity of HIV-1inhibitor peptides is increased bythe addition of cholesterol and polyethylene glycol (PEG). The aim of the present work isto characterizethe interaction of enfuvirtide derived molecules by conjugation with cholesterol,palmitic acid or α-tocopherol as lipid anchors and PEG as spacer, with biomembrane model systems and human blood cells.Fluorescence spectroscopymethodologies, including membrane partition and fluorescence quenching assays,demonstrated that conjugation with lipids increasesthe peptides ability to interact with membranes of different compositions. In addition, the depth of peptide insertion into the membrane was assessed using lipophilic probes, revealing that the conjugated peptides are located in a more shallow position than the unconjugated one. Moreover, dipole potential assays showed that conjugated peptides exhibit a higher affinity towards cholesterol-rich membranes, as well as human blood cells, than the unconjugated peptide.Altogether, the obtained results indicate that a proper balance between membrane affinity and peptide exposure is required in order to enhance antiviral activity. Therefore, the addition of lipid moieties to an established fusion inhibitor such as enfuvirtide can be a promising strategy against HIV-1
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