ABSTRACT
Zika virus (ZIKV) has been associated with serious health conditions, and an intense search to discover different ways to prevent and treat ZIKV infection is underway. Berberine and emodin possess several pharmacological properties and have been shown to be particularly effective against the entry and replication of several viruses. We show that emodin and berberine trigger a virucidal effect on ZIKV. When the virus was exposed to 160 µM of berberine, a reduction of 77.6% in the infectivity was observed; when emodin was used (40 µM), this reduction was approximately 83.3%. Dynamic light scattering data showed that both compounds significantly reduce the hydrodynamic radius of virus particle in solution. We report here that berberine and emodin, two natural compounds, have strong virucidal effect in Zika virus.
Subject(s)
Antiviral Agents/pharmacology , Biological Products/pharmacology , Plants, Medicinal/chemistry , Zika Virus/drug effects , Animals , Antiviral Agents/isolation & purification , Berberine/pharmacology , Biological Products/isolation & purification , Chlorocebus aethiops , Emodin/pharmacology , Medicine, East Asian Traditional , Vero Cells , Virion/drug effects , Virus Replication/drug effectsABSTRACT
During ZIKV the outbreak in Brazil it was observed an increase of almost 20 times the number of reported cases of microcephaly in newborn babies. There is no vaccine or approved drug available for the treatment and prevention of infections by this virus. EGCG, a polyphenol present in green tea has been shown to have an antiviral activity for many viruses. In view of the need for the development of a drug against a Brazilian strain of ZIKV, we assessed the effect of EGCG on ZIKV entry in Vero E6 cells. The drug was capable of inhibiting the virus entry by at least 1-log (>90%) at higher concentrations (>100µM). The pre-treatment of cells with EGCG did not show any effect on virus attachment. This is the first study to demonstrate the effect of EGCG on ZIKV indicating that this drug might be possibility to be used for prevention of Zika virus infections.
Subject(s)
Antiviral Agents/pharmacology , Catechin/analogs & derivatives , Plant Extracts/pharmacology , Tea/chemistry , Virus Internalization/drug effects , Zika Virus/drug effects , Zika Virus/physiology , Animals , Antiviral Agents/chemistry , Catechin/chemistry , Catechin/pharmacology , Cell Survival , Cells, Cultured , Chlorocebus aethiops , Dose-Response Relationship, Drug , Molecular Structure , Plant Extracts/chemistry , Vero CellsABSTRACT
Conjugate compounds constitute a new class of molecules of important biological interest mainly for the treatment of diseases such as cancer. The N-terminus region of cationic peptides has been described as important for their biological activity. The aim of this study was to evaluate the lytic peptide Hecate (FALALKALKKALKKLKKALKKAL) and the effect of conjugating this macromolecule with gallic acid (C7H6O5) in terms of structure, anti-cancer activity, and toxicity. An N-terminus GA-Hecate peptide conjugate was synthesized to provide information regarding the relationship between the amino-terminal region and its charge and the secondary structure and biological activity of the peptide; and the effects of gallic acid on these parameters. Peptide secondary structure was confirmed using circular dichroism (CD). The CD measurements showed that the peptide has a high incidence of α-helical structures in the presence of SDS and LPC, while GA-Hecate presented lower incidence of α-helical structures in the same chemical environment. An evaluation of the anti-cancer activity in HeLa cancer cells indicated that both peptides are active, but that coupling gallic acid at the N-terminus decreased the activity of the free peptide. GA-Hecate showed lower activity in non-tumor keratinocyte cells but higher hemolytic activity. Our findings suggest that the N-terminus of Hecate plays an important role in its activity against cervical cancer by affecting it secondary structure, toxicity, and hemolytic activity. This study highlights the importance of the N-terminus in antitumor activity and could provide an important tool for developing new anti-cancer drugs.
Subject(s)
Antineoplastic Agents/pharmacology , Gallic Acid/pharmacology , Hemolytic Agents/pharmacology , Melitten/analogs & derivatives , Amino Acid Sequence , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Erythrocytes/drug effects , Female , HeLa Cells , Humans , Melitten/pharmacology , Molecular Sequence Data , Uterine Cervical NeoplasmsABSTRACT
Hepatitis C is considered the major cause of cirrhosis and hepatocellular carcinoma. Conventional treatment is not effective against some hepatitis C virus (HCV) genotypes; therefore, new treatments are needed. Coffee and, more recently, caffeine, have been found to have a beneficial effect in several disorders of the liver, including those manifesting abnormal liver biochemistry, cirrhosis and hepatocellular carcinoma. Caffeine acts directly by delaying fibrosis, thereby improving the function of liver cellular pathways and interfering with pathways used by the HCV replication cycle. In the current study, the direct relationship between caffeine and viral replication was evaluated. The Huh-7.5 cell line was used for transient infections with FL-J6/JFH-5'C19Rluc2AUbi and to establish a cell line stably expressing SGR-Feo JFH-1. Caffeine efficiently inhibited HCV replication in a dose-dependent manner at non-cytotoxic concentrations and demonstrated an IC50 value of 0.7263 mM after 48 h of incubation. These data demonstrate that caffeine may be an important new agent for anti-HCV therapies due to its efficient inhibition of HCV replication at non-toxic concentrations.
