Progress in the development and application of plant-based antiviral agents

Plant virus disease is one of the major causes of biological disasters in agriculture worldwide. Given the complexity of transmission media and plant disease infection mechanisms, the prevention and control of plant viral diseases is a great challenge, and an efficient green pesticide is urgently needed. For this reason, when developing candidate drug leads to regulate plant viruses, pesticide experts have focused on characteristics such as low pesticide resistance, eco-friendliness, and novel mechanism. Researchers have also theoretically investigated the molecular targets of viruses infecting agricultural crops. Antiviral screening models have been constructed based on these molecular targets, and the mechanisms of commercial drugs and high-activity compounds have been extensively investigated. After screening, some compounds have been applied in the field and found to have good commercial prospects; these drugs may be used to create new green antiviral pesticides to control plant viruses. This paper reviews the screening, mode of action, development and application of recently used plant-based antiviral agents.

Helicobacter pylori neutrophil-activating protein:From molecular pathogenesis to clinical applications

Helicobacter pylori (H. pylori) neutrophil-activating protein (HP-NAP) was originally identified as a virulence factor of H. pylori for its ability to activate neutrophils to generate respiratory burst by releasing reactive oxygen species. Later on, HP-NAP was also found to be involved in the protection of H. pylori from DNA damage, supporting the survival of H. pylori under oxidative stress. This protein is highly conserved and expressed by virtually all clinical isolates of H. pylori. The majority of patients infected with H. pylori produced antibodies specific for HP-NAP, suggesting its important role in immunity. In addition to acting as a pathogenic factor by activating the innate immunity through a wide range of human leukocytes, including neutrophils, monocytes, and mast cells, HP-NAP also mediates adaptive immunity through the induction of T helper cell type I responses. The pro-inflammatory and immunomodulatory properties of HP-NAP not only make it play an important role in disease pathogenesis but also make it a potential candidate for clinical use. Even though there is no convincing evidence to link HP-NAP to a disease outcome, recent findings supporting the pathogenic role of HP-NAP will be reviewed. In addition, the potential clinical applications of HP-NAP in vaccine development, clinical diagnosis, and drug development will be discussed.

Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development

Drug metabolism and pharmacokinetics(DMPK) is an important branch of pharmaceutical sciences.The nature of ADME(absorption,distribution,metabolism,excretion) and PK(pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems.Tremendous progress has been made in the past decade,not only in the characterization of physiochemical properties of drugs that influence their ADME,target organ exposure,and toxicity,but also in the identification of design principles that can minimize drug-drug interaction(DDI) potentials and reduce the attritions.The importance of membrane transporters in drug disposition,efficacy,and safety,as well as the interplay with metabolic processes,has been increasingly recognized.Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs,such as peptides,oligonucleotides,and antibody-drug conjugates,necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties.In this review,we highlight some of the most notable advances in the last decade,and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.

Development of the generic drug industry in the US after the Hatch-Waxman Act of 1984

The key events in the development of the US generic drug industry after the Hatch-Waxman Act of 1984 are systematically reviewed,including the process of approval for generic drugs,bioequivalence issues including“switchability”,bioequivalence for complicated dosage forms,patent extension,generic drug safety,generic substitution and low-cost generics.The backlog in generic review,generic drug user fees,and“quality by design”for generic drugs is also discussed.The evolution of the US generic drug industry after the Hatch-Waxman Act in 1984 has afforded several lessons of great benefit to other countries wishing to establish or re-establish a domestic generic drug industry.

Brief introduction for application of USA authorized generic drugs

The authorized generic drugs(AGs)are drug products marketed in the USA with the permission of sponsor or holder of the approved brand name drug(usually refers to an innovator drug).Other than the fact that it does not have the brand name on its label,it is the exact same drug product as the brand name product.In China,for those published comparator products of generic drug products,the market availability is the first question to affect the smooth development and investigation for the process of the re-evaluation of the generic drugs.In the present paper,we systemically elaborated the definition,classification and relevant background of the AGs,as well as their differences to the generic drugs.At the same time,by taking drug products,which are adopted in the Chinese comparator product directories for generic medicinal products(first batch)and sourced from USA orange book,as examples,we introduced the searching process of the AGs with the integration of FDA listing of AGs,the USA orange book and the USA national drug code directory.It can facilitate the domestic and foreign pharmaceutical enterprises to search,identify and purchase the corresponding AGs of the designated comparator product when question emerges to its market availability.

Recent advances in alginate based gastroretentive technologies for drug delivery applications

The efficacy of orally delivered medicines can be maximized through enhancing the gastric residence period and modifying the drug release pattern according to therapeutic need.Several technologies were investigated through recent years for increasing gastric retention of medicines.Biopolymers are one of the widely studied materials for increasing the retention of drug delivery systems in the stomach region.The biodegradability,biocompatibility and non-toxic behavior in combination with the easy fabrication technologies has made biopolymers an interesting option to pharmaceutical scientists for developing gastroretentive drug delivery systems(GRDDS).Several gastroretentive approaches are reported to be efficacious to localize the drug delivery system in the gastric region.Alginates are commonly employed polysaccharide for developing various GRDDS including low density systems,mucoadhesive systems,swellable systems,hydrogel forming systems,in situ gelling systems,raft forming systems,magnetic systems.The abundant availability from marine and bacterial sources in combination with its attractive physicochemical nature has encouraged pharmaceutical researchers to investigate its suitability in developing various drug delivery system.The mucoadhesive,hydrogel forming and raft forming behavior of alginates makes alginate suitable for GRDDS.The attractive properties of alginate makes it a useful biopolymer in the biomedical field.This review focuses on the source and chemistry of alginates and describes the applications of alginates in developing novel gastroretentive drug delivery systems.