Sargassum filipendula, a Source of Bioactive Compounds with Antioxidant and Matrix Metalloproteinases Inhibition Activities In Vitro with Potential Dermocosmetic Application.

The antioxidant and the potential inhibitory capacity of matrix metalloproteinases of the phlorotannin-type polyphenolic and fucoidan-type polysaccharides extracts obtained from the macroalga S. filipendula were evaluated. Through chromatographic and spectroscopic techniques, the corresponding chemical structure of compounds present in the extracts was determined. Antioxidant capacity was evaluated using the methyl linoleate model for the inhibition of lipid peroxidation, and the free radical scavenging capacity was assessed using DPPH, ABTS, •OH, O2•- methods. The matrix metalloproteinase inhibition potential was measured by collagenase and elastase inhibition tests, using epigallocatechin gallate as a positive control. The extracts exhibited a high scavenging capacity of radical species evaluated and inhibition of diene conjugate formation and thiobarbituric acid reactive substances. The results showed that the crude extracts presented dose-dependent collagenase and elastase inhibition, with IC50 values between 0.04 and 1.61 mg/mL. The structure of the residues of the polysaccharide was identified mainly as (1→3)-sulfated (1→3) α-l-fucopyranose at carbon 4 and residues of ß-d-glucopyranose, α-d-Mannopyranose, and ß-d-Galactopyranose, while in the polyphenol extract the presence of phloroglucinol was identified and the presence of eckol, bifuhalol, and trifuhalol was suggested. Our results allow us to infer that S. filipendula is a potential source of bioactive ingredients with antioxidant and anti-aging activity.

Deubiquitinating Enzyme Inhibitors Block Chikungunya Virus Replication.

Ubiquitination and deubiquitination processes are widely involved in modulating the function, activity, localization, and stability of multiple cellular proteins regulating almost every aspect of cellular function. Several virus families have been shown to exploit the cellular ubiquitin-conjugating system to achieve a productive infection: enter the cell, promote genome replication, or assemble and release viral progeny. In this study, we analyzed the role of deubiquitinating enzymes (DUBs) during chikungunya virus (CHIKV) infection. HEK293T, Vero-E6, and Huh-7 cells were treated with two DUB inhibitors (PR619 or WP1130). Then, infected cells were evaluated by flow cytometry, and viral progeny was quantified using the plaque assay method. The changes in viral proteins and viral RNA were analyzed using Western blotting and RT-qPCR, respectively. Results indicate that treatment with DUB inhibitors impairs CHIKV replication due to significant protein and viral RNA synthesis deregulation. Therefore, DUB activity may be a pharmacological target for blocking CHIKV infection.

Molecular and biological characterization of an Asian-American isolate of Chikungunya virus.

Chikungunya virus is an arthropod-transmitted virus that causes chikungunya fever, a disease characterized by severe muscle and joint pain. In 2013, the virus was introduced to the Americas and caused approximately 2.7 million cases of infection during the subsequent two years. The lack of knowledge regarding the biological behavior of the viral strains circulating during the outbreak motivated the characterization of an isolate from the Colombian outbreak, starting from analysis of the complete genome to the biological behavior in vitro. The full genome was retrieved using next-generation sequencing. The infective and replicative capacities were evaluated in HEK293T, Huh-7, and MRC-5 cell lines. The infection rates were determined by flow cytometry, and the cytopathic effect was assessed by a resazurin fluorescent metabolic assay. The viral yield was quantified using the virus plaque formation assay, while the viral proteins and genomic RNA kinetics were subsequently evaluated by western-blot and RT-qPCR. The COL7624 isolate clustered with other American and Caribbean sequences in the Asian American lineage. The T669A substitution in E2 protein distinguished it from other Colombian sequences reported in 2014. After 48 h post infection (hpi), the three cell lines analyzed reached infection percentages exceeding 65%, generating a high load of infectious viral progeny. The infection kinetics indicated that the replication peak of this CHIKV isolate is around 24 hpi, although gRNA is detectable in the culture supernatant from 4 hpi onwards. The infection caused the overexpression of interferon and pro-inflammatory cytokines, such as IL-1ß, TNF-α, and IL-8. The COL7624 CHIKV isolate exhibited a high infective and replicative capacity as well as activation of cellular immune responses, similar to isolates belonging to the other genotypes.

Rediscovering the chikungunya virus / [Reconociendo el virus del chikunguña].

The chikungunya virus (CHIKV) is an Alphavirus that belongs to the Old World group. These arthritogenic viruses cause a febrile illness characterized by arthralgias and myalgias. Although fatal cases during CHIKV infection are rare, the disease may be disabling and generate a broad spectrum of atypical manifestations, such as cardiovascular, respiratory, eye, kidney, and skin complications, among others. When joint pain persists for three or more months, it results in the chronic form of the disease called post-chikungunya chronic inflammatory rheumatism, which constitutes the main disease sequel. CHIKV is not considered a neurotropic virus; however, it can affect the central nervous system, especially in children and the elderly, causing severe and permanent sequelae. CHIKV outbreaks had been previously reported in Africa, Asia, and Europe, but the virus introduction to the American continent was documented until the end of 2013. Since then, the irus has spread to 45 countries and territories causing near two million cases in just two years. This review describes the molecular biology, clinical manifestations, pathogenesis, and significant post-infection complications of CHIKV. Additionally, it collects published information about the outbreak in Colombia and the American continent between 2014 and 2020.

El virus de chikunguña (CHIKV) es un Alfavirus perteneciente al grupo denominado del Viejo Mundo; estos son virus artritogénicos que causan una enfermedad febril caracterizada por artralgias y mialgias. Aunque la muerte por CHIKV es poco frecuente, la enfermedad puede llegar a ser incapacitante y generar un amplio espectro de manifestaciones atípicas, como complicaciones cardiovasculares, respiratorias, oculares, renales y dérmicas, entre otras. Cuando el dolor articular persiste por tres o más meses, da lugar a la forma crónica de la enfermedad denominada reumatismo inflamatorio crónico poschikunguña, el cual es la principal secuela de la enfermedad. Se considera que este virus no es neurotrópico, sin embargo, puede afectar el sistema nervioso central y generar secuelas graves y permanentes, principalmente, en niños y ancianos. En África, Asia y Europa se habían reportado anteriormente brotes epidémicos por CHIKV, pero solo hasta finales del 2013 se documentó la introducción del virus a las Américas; desde entonces, el virus se ha propagado a 45 países o territorios del continente y el número de casos acumulados ascendió a cerca de dos millones en dos años. Esta revisión describe de manera general la biología molecular del virus, sus manifestaciones clínicas, su patogénesis y las principales complicaciones posteriores a la infección. Además, reúne la información de la epidemia en Colombia y el continente americano publicada entre el 2014 y el 2020.

Reconociendo el virus del chikunguña / Rediscovering the chikungunya virus

Resumen | El virus de chikunguña (CHIKV) es un Alfavirus perteneciente al grupo denominado del Viejo Mundo; estos son virus artritogénicos que causan una enfermedad febril caracterizada por artralgias y mialgias. Aunque la muerte por CHIKV es poco frecuente, la enfermedad puede llegar a ser incapacitante y generar un amplio espectro de manifestaciones atípicas, como complicaciones cardiovasculares, respiratorias, oculares, renales y dérmicas, entre otras. Cuando el dolor articular persiste por tres o más meses, da lugar a la forma crónica de la enfermedad denominada reumatismo inflamatorio crónico poschikunguña, el cual es la principal secuela de la enfermedad. Se considera que este virus no es neurotrópico, sin embargo, puede afectar el sistema nervioso central y generar secuelas graves y permanentes, principalmente, en niños y ancianos. En África, Asia y Europa se habían reportado anteriormente brotes epidémicos por CHIKV, pero solo hasta finales del 2013 se documentó la introducción del virus a las Américas; desde entonces, el virus se ha propagado a 45 países o territorios del continente y el número de casos acumulados ascendió a cerca de dos millones en dos años. Esta revisión describe de manera general la biología molecular del virus, sus manifestaciones clínicas, su patogénesis y las principales complicaciones posteriores a la infección. Además, reúne la información de la epidemia en Colombia y el continente americano publicada entre el 2014 y el 2020.

Abstract | The chikungunya virus (CHIKV) is an Alphavirus that belongs to the Old World group. These arthritogenic viruses cause a febrile illness characterized by arthralgias and myalgias. Although fatal cases during CHIKV infection are rare, the disease may be disabling and generate a broad spectrum of atypical manifestations, such as cardiovascular, respiratory, eye, kidney, and skin complications, among others. When joint pain persists for three or more months, it results in the chronic form of the disease called post-chikungunya chronic inflammatory rheumatism, which constitutes the main disease sequel. CHIKV is not considered a neurotropic virus; however, it can affect the central nervous system, especially in children and the elderly, causing severe and permanent sequelae. CHIKV outbreaks had been previously reported in Africa, Asia, and Europe, but the virus introduction to the American continent was documented until the end of 2013. Since then, the virus has spread to 45 countries and territories causing near two million cases in just two years. This review describes the molecular biology, clinical manifestations, pathogenesis, and significant post-infection complications of CHIKV. Additionally, it collects published information about the outbreak in Colombia and the American continent between 2014 and 2020.