Current Drug Metabolism - Volume 19, Issue 3, 2018

Background: Noroviruses and rotaviruses are important viral etiologies of severe gastroenteritis. Noroviruses are the primary cause of nonbacterial diarrheal outbreaks in humans, whilst rotaviruses are a major cause of childhood diarrhea. Although both enteric pathogens substantially impact human health and economies, there are no approved drugs against noroviruses and rotaviruses so far. On the other hand, whilst the currently licensed rotavirus vaccines have been successfully implemented in over 100 countries, the most advanced norovirus vaccine has recently completed phase-I and II trials. Methods: We performed a structured search of bibliographic databases for peer-reviewed research literature on advances in the fields of norovirus and rotavirus therapeutics and immunoprophylaxis. Results: Technological advances coupled with a proper understanding of viral morphology and replication over the past decade has facilitated pioneering research on therapeutics and immunoprophylaxis against noroviruses and rotaviruses, with promising outcomes in human clinical trials of some of the drugs and vaccines. This review focuses on the various developments in the fields of norovirus and rotavirus therapeutics and immunoprophylaxis, such as potential antiviral drug molecules, passive immunotherapies (oral human immunoglobulins, egg yolk and bovine colostral antibodies, llama-derived nanobodies, and antibodies expressed in probiotics, plants, rice grains and insect larvae), immune system modulators, probiotics, phytochemicals and other biological substances such as bovine milk proteins, therapeutic nanoparticles, hydrogels and viscogens, conventional viral vaccines (live and inactivated whole virus vaccines), and genetically engineered viral vaccines (reassortant viral particles, virus-like particles (VLPs) and other subunit recombinant vaccines including multi-valent viral vaccines, edible plant vaccines, and encapsulated viral particles). Conclusions: This review provides important insights into the various approaches to therapeutics and immunoprophylaxis against noroviruses and rotaviruses.

Background: Prosopis cineraria (L.) Druce ('khejri') is an important tree that occurs worldwide in arid regions. It has been mentioned in the Indian Ayurvedic system of medicines as having several clinical properties. Different parts of this plant are used in India, Pakistan, Bangladesh, the United Arab Emirates, Saudi Arabia and Iran for treating various ailments such as leprosy, leucoderma, dysentery, asthma, bronchitis, piles, jaundice and muscular tremors. Since all parts of the tree are useful, it is called ‘Kalp Taru’ or ‘Wonder Tree’ in India. Phytochemical studies of P. cineraria have underlined the presence of various classes of phytochemicals, such as flavone derivatives (prosogerin A, B, C, D and E), alkaloids (spicigerine and prosophylline), tannins (gallic acid), steroids (stigmasterol, campesterol and sitosterol, etc.), fatty acids and amino acids, etc., that have been obtained from different parts of the plant. Methods: We undertook a comprehensive, critical and systematic literature survey on ethnomedicinal, phytochemical and pharmacological aspects of P. cineraria. Efforts were made to establish/corroborate the scientific reasons of ethnomedicinal use with the help of published modern studies. Results: Based on in-depth analysis of more than 200 studies, we were able to corroborate a large number of facts pertaining to uses of different parts of this plant for treating various maladies. Further, it yielded several new insights on phyto-pharmacological aspects of P. cineraria. Conclusion: Results of this study are useful for commercialization of the products derived from phytochemicals of P. cineraria.

Background: Interleukin-28B (IL28B) locus on a human chromosomal region mapped to 19q13 execute immune defense against viruses. During Hepatitis C Virus (HCV) infection the IL28B has a promising role in deciding the consequence of infection for spontaneous clearance of viruses or causing chronic liver infection. Treatment of chronic hepatitis C includes use of direct acting antivirals, Pegylated-Interferon (PEG-IFN) and Ribavirin (RBV) therapy. Also, interferon free regimens are suggested to be useful in resistant patients. Numerous reports including Genome-Wide Association Studies (GWAS), comprehensive meta-analysis and independent case-control studies in different population have revealed the association between certain Il-28B polymorphisms and response to the PEGIFN- RBV therapy in patients infected with HCV. Method: We searched all peer-reviewed relevant and recent literature manually for the present review. Conclusion: The GWAS studies have revealed an important role of IL28B in HCV infection, which was supported by many independent studies and meta-analysis by different groups in different ethnicities. IL28B genotyping may be use as predictors of response for IFN-based therapy and personalized treatment of hepatitis C patient.

Background: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer associated deaths. Prognosis is relatively poor in cases where Hepatitis C Virus (HCV) is associated as causative agent, mainly due to increased risk of metastasis. Metastasis is the major cause of all cancer related deaths. Methods: We reviewed reports linking expression of HCV encoded proteins with changes in cellular functions. We also compared reports on HCV-induced HCC with those on non-viral and Hepatitis B Virus (HBV) induced HCC. Novel therapeutic approaches for handling metastatic HCC were also reviewed. Results: HCV infection is associated with expression of multiple pro-metastatic factors in HCC patients. HCV encoded proteins can directly induce pro-metastasis cellular functions. HCV-induced HCC has a greater chance of recurrence than any non-viral and Hepatitis B Virus (HBV) induced HCC. Recent advances in understanding of evolutionary dynamics of tumor argue that trying to prevent spreading of cancer may ultimately prove to be a better approach than striving to cure it. Inhibiting the metastasis can thereby substantially increase the survival period in patients. Host cell protein Nm23-H1 is a known suppressor of tumor metastasis and has been shown to be modulated by proteins encoded by different viruses associated with cancers. Conclusion: Nm23-H1 is an important therapeutic target for virus mediated malignancies. This review is an attempt to summarize the current state of understanding of cancer cell metastasis in HCV induced tumors, and argues for approaches based on targeting host and viral factors critical for cancer metastasis as therapeutic targets.

Background: Recently, there has been a remarkable progress in the field of antiviral herbal therapy owing to increasing concerns about the development of drug resistance and limited advances in the field of antiviral drug discovery. In almost all countries, medicinal plants have been used widely throughout history for the treatment of diseases and infections as traditional healing remedies due to their broad therapeutic spectrum and minimal or no side effects. As synthetic antiviral drugs are not available against most of the viral agents, hence all possible efforts have been focused on the search for new drugs and complementary/alternative medicines from different herbal formulations. Methods: We have retrieved the related information from the online published resources (Medline, PubMed, Pub- Med Central, Science Direct and other scientific databases); which were further analyzed and compiled. Results: Medicinal plants contain extractable biochemical and bioactive compounds, which can target certain viruses or can cure or prevent several viral diseases and infections. Despite their long history of use, the research and scientific evidences regarding the use of medicinal plants and natural products as prophylactics, therapeutics, and their health multiple beneficial applications have only gained momentum in past few decades. Many scientific studies have been undertaken, which range from the separation of active substances to the comprehension of the therapeutic mechanisms of antiviral herbs, their potent applications in the neutralization of viral pathogens and clinical trials. Consequently, hundreds of herbs and plant metabolites have been screened, identified, and tested for their antiviral activities; fortunately, some have shown significant medicinal activity in the amelioration or prevention of various viral diseases in both preclinical and clinical studies. Conclusion: This review addresses the scientific significance of various herbal formulations of different medicinal plants and their extracts, which have shown promise or been proven effective for the treatment of diseases caused by various viral pathogens, including emerging and re-emerging viruses that infect humans, animals, poultry and fish.

Background: Constant exposure to various stressors, such as immune pressure, rapidly increasing population, deleterious changes in the ecosystem, climate change, infection with emerging and re-emerging pathogens, and fast-paced lifestyle, is a critical factor in the globally increasing incidences of immunocompromising health conditions, as well as stress. Synthetic chemotherapeutic agents, which are widely available in the commercial market, may be highly efficacious, but most are immunosuppressive and exert many side effects. Methods: Herein, we comprehensively reviewed current literature from various scientific databases such as Bentham Science, PubMed, Scopus, Elsevier, Springer, etc. The inclusion/exclusion criteria based on literature with high importance was adopted to analyze and compile salient information from the authentic bibliographic sources. Results: Undoubtedly, the pivotal characteristics of immunostimulants and immunomodulators in the maintenance of the health and productivity of humans, as well as animals, cannot be overlooked. Numerous herbs used in ethnoveterinary medicine can be successfully employed as adjuvant rehabilitators to negate the deleterious effects of chemotherapeutics. The sources of these medicinal remedies are part of long traditions in different regions of the world, such as Indian Ayurveda and Traditional Chinese Medicine, which have been developed through empirical experience. Traditional medicine employs a holistic approach to the prevention of disease, and traditional herbal medicines are a source of many components with a high therapeutic value that are used in modern allopathic medicine. Globally, many studies have been conducted on these herbs and have revealed unique active constituents that activate the innate immune system through the stimulation of macrophages and lymphocytes, and modulation of the cytokine profile, which leads to a state of alertness with a subsequent reduction in the incidence of infection. Immunomodulatory constituents with herbal origins are termed as phytochemicals, including flavonoids, glycosides, polysaccharides, terpenoids, essential oils, various bitters, and alkaloids; all these compounds exert vital, multidimensional effects. Efforts have focused on screening plant preparations to identify adjuvant immune properties; furthermore, several potent phytol adjuvants have been experimentally proven to downregulate inflammatory reactions in addition to enhance specific adaptive responses to vaccines. Conclusions: In summary, this review summarizes the current status and future prospects regarding the immunomodulatory potential of various herbs and plants and their promising utility for designing and developing effective drugs and medicines in safeguarding the health of humans, animals, and poultry.