RESUMO
In Gordts et al. (2015), we have shown that lignosulfonic acid, a commercially available lignin derivative, possesses broad antiviral activity against human immunodeficiency virus (HIV) and Herpes simplex virus (HSV) by preventing viral entry into susceptible target cells. Because of the interesting safety profile as potential microbicide, we now determined the antiviral activity of a series of lignosulfonates in order to understand better which molecular features can contribute to their antiviral activity. Here, 24 structurally different lignosulfonates were evaluated for their capacity to inhibit HIV and HSV transmission and replication in various cellular assays. These derivatives differ in origin (hardwood or softwood), counter-ion used during sulphite processing (Na+, Ca2+, or NH4+), sulphur content, carboxylic acid percentage, and molecular weight fraction, which allowed to determine structure-activity relationships. We demonstrate that the broad antiviral activity of lignosulfonates is mainly dependent on their molecular weight and that their mechanism of action is based on interactions with the viral envelope glycoproteins. This makes the lignosulfonates a potential low-cost microbicide that protects women from sexual HIV and HSV transmission and thus prevents life-long infection.
Assuntos
Antivirais/farmacologia , Infecções por HIV/prevenção & controle , HIV/efeitos dos fármacos , Lignina/análogos & derivados , Animais , Antivirais/química , Linhagem Celular , Infecções por HIV/transmissão , Herpes Simples/prevenção & controle , Herpes Simples/transmissão , Herpesvirus Humano 2/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Lignina/química , Lignina/farmacologia , Fusão de Membrana/efeitos dos fármacos , Estrutura Molecular , Peso Molecular , Proteínas do Envelope Viral/química , Internalização do Vírus/efeitos dos fármacosRESUMO
Amphipathic lignin derivatives (A-LDs) prepared from the black liquor of soda pulping of Japanese cedar are strong accelerators for bioethanol production under a fed-batch simultaneous enzymatic saccharification and fermentation (SSF) process. To improve the bioethanol production concentration, conditions such as reaction temperature, stirring program, and A-LDs loadings were optimized in both small scale and large scale fed-batch SSF. The fed-batch SSF in the presence of 3.0g/L A-LDs at 38°C gave the maximum ethanol production and a high enzyme recovery rate. Furthermore, a jar-fermenter equipped with a powerful mechanical stirrer was designed for 1.5L-scale fed-batch SSF to achieve rigorous mixing during high substrate loading. Finally, the 1.5L fed-batch SSF with a substrate loading of 30% (w/v) produced a high ethanol concentration of 87.9g/L in the presence of A-LDs under optimized conditions.