Ashok Munjal

Advances in Developing Therapies to Combat Zika Virus: Current Knowledge and Future Perspectives

Zika virus (ZIKV) remained largely quiescent for nearly six decades after its first appearance in 1947. ZIKV reappeared after 2007, resulting in a declaration of an international “public health emergency” in 2016 by the World Health Organization (WHO). Until this time, ZIKV was considered to induce only mild illness, but it has now been established as the cause of severe clinical manifestations, including fetal anomalies, neurological problems, and autoimmune disorders. Infection during pregnancy can cause congenital brain abnormalities, including microcephaly and neurological degeneration, and in other cases, Guillain-Barré syndrome, making infections with ZIKV a substantial public health concern. Genomic and molecular investigations are underway to investigate ZIKV pathology and its recent enhanced pathogenicity, as well as to design safe and potent vaccines, drugs, and therapeutics. This review describes progress in the design and development of various anti-ZIKV therapeutics, including drugs targeting virus entry into cells and the helicase protein, nucleosides, inhibitors of NS3 protein, small molecules, methyltransferase inhibitors, interferons, repurposed drugs, drugs designed with the aid of computers, neutralizing antibodies, convalescent serum, antibodies that limit antibody-dependent enhancement, and herbal medicines. Additionally, covalent inhibitors of viral protein expression and anti-Toll-like receptor molecules are discussed. To counter ZIKV-associated disease, we need to make rapid progress in developing novel therapies that work effectually to inhibit ZIKV.

Green tea (Camellia sinensis) and l-theanine: Medicinal values and beneficial applications in humans—A comprehensive review

Green tea (Camellia sinensis) is a famous herb, and its extract has been extensively used in traditional Chinese medicinal system. In this context, several studies have revealed its health benefits and medicinal potentialities for several ailments. With ever increasing scientific knowledge, search for safer, potential and novel type of health-related supplements quest, scientists are re-directing their research interests to explore natural resources i.e. medicinal herbs/plant derived compounds. Green tea consumption has gained a special attention and popularity in the modern era of changing lifestyle. The present review is aimed to extend the current knowledge by highlighting the importance and beneficial applications of green tea in humans for safeguarding various health issues. Herein, we have extensively reviewed, analyzed, and compiled salient information on green tea from the authentic published literature available in PubMed and other scientific databases. Scientific literature evidenced that owing to the bioactive constituents including caffeine, l-theanine, polyphenols/flavonoids and other potent molecules, green tea has many pharmacological and physiological functions. It possesses multi-beneficial applications in treating various disorders of humans. This review also provides in-depth insights on the medicinal values of green tea which will be useful for researchers, medical professionals, veterinarians, nutritionists, pharmacists and pharmaceutical industry. Future research emphasis and promotional avenues are needed to explore its potential therapeutic applications for designing appropriate pharmaceuticals, complementary medicines, and effective drugs as well as popularize and propagate its multidimensional health benefits.

Recent Trends in Nanotechnology-Based Drugs and Formulations for Targeted Therapeutic Delivery

BACKGROUND In the recent past, a wider spectrum of nanotechnologybased drugs or drug-loaded devices and systems has been engineered and investigated with high interests. OBJECTIVE The key objective is to help for an enhanced/better quality of patient life in a secure way by avoiding/limiting drug abuse, or severe adverse effects of some in practice traditional therapies. METHOD Various methodological approaches including in vitro, in vivo, and ex vivo techniques have been exploited, so far. Among them, nanoparticles-based therapeutic agents are of supreme interests for an enhanced and efficient delivery in the current biomedical sector of the modern world. RESULTS The development of new types of novel, effective and highly reliable therapeutic drug delivery system (DDS) for multipurpose applications is essential and a core demand to tackle many human health related diseases. In this context, nanotechnology-based several advanced DDS have been engineered with novel characteristics for biomedical, pharmaceutical and cosmeceutical applications that include but not limited to the enhanced/improved bioactivity, bioavailability, drug efficacy, targeted delivery, and therapeutically safer with an extra advantage of overcoming demerits of traditional drug formulations/designs. This review work is focused on recent trends/advances in nanotechnology-based drugs and formulations designed for targeted therapeutic delivery. Moreover, information is also reviewed and given from recent patents and summarized or illustrated diagrammatically to depict a better understanding. Recent patents covering various nanotechnology-based approaches for several applications have also been reviewed. CONCLUSION The drug-loaded nanoparticles are among versatile candidates with multifunctional characteristics for potential applications in biomedical, and tissue engineering sector.

Advances in Aquaculture Vaccines Against Fish Pathogens: Global Status and Current Trends

ABSTRACT In recent years, aquaculture has attained a major economic revolution, however, infectious diseases of bacterial, viral, mycotic and parasitic origin are the most significant restrictive agents in the improvement of intensified aquaculture, which has become a fast blooming seafood industry. For environment-friendly aquaculture and human health concerns owing to the rise in incidences of antimicrobial resistant microbes and food safety hazards, the immunoprophylaxis or vaccination strategies are highly effective and economical in protecting the health of fish and aquaculture animals from various infectious agents. Advancements in science have paved newer avenues in both basic and applied research areas for developing and designing novel and effective vaccines, as well as improving existing vaccines for rendering protection from various types of infectious diseases. Current advances in vaccines and vaccinology offer valuable opportunities to discover new vaccine candidates to combat fish pathogens, including mycotic and parasitic agents, for which vaccines are still lacking. This review focuses on the current knowledge, recent advances and future perspectives of vaccines and vaccination in the aquaculture industry, from traditional inactivated and attenuated vaccines to new generation vaccines comprising of recombinant, subunit, vectored, genetically engineered, DNA and peptide vaccines, reverse vaccinology and plant-based edible vaccines, and nanovaccines.

Heat Shock Proteins: Therapeutic Perspectives in Inflammatory Disorders.

BACKGROUND Heat shock proteins (HSPs) are highly conserved proteins present in all kingdoms of organisms. These are expressed under stress conditions in order to protect the cells from injuries. The stress induced protein denaturation is rectified by refolding and remodelling. These are intracellular proteins but can be present in extracellular fluid like serum of the patients suffering from trauma, autoimmune and inflammatory disorders. Virtually in most inflammatory diseases, immune response towards HSPs is developed. OBJECTIVE The present review expedites the role of HSPs in inflammatory process and associated disorders, mainly in context to HSP70 and HSP90. METHOD Commencing a thorough survey of the literature and patents available on HSPs and their role in the process of inflammation, from the authentic published resources available on Medline, Pubmed, Pubmed Central, Science Direct and other scientific databases; the information retrieved has been compiled and analyzed. RESULTS HSPs modulate the process of inflammation by producing anti-inflammatory cytokines in chronic inflammatory disease. HSPs mediated expression of IL10 contributes in anti-inflammatory role via TLR2 and TLR4-dependent mechanisms. Necroptosis, a caspase independent programmed apoptosis plays an important role in progression of several inflammatory disorders and its major components MLKL and RIPK-1 are the clients of HSP. Necroptosis is also involved in exposure of several damageassociated molecular patterns (DAMPs) including HSPs in extracellular environment leading to inflammation. Endocytosed or intracellular HSP70, is presented by MHC-II molecules and in absence of proper co stimulation, it lead to expansion of tolerogenic or regulatory T cells (Tregs) responses, which have inflammation suppressive activity by virtue of production of anti-inflammatory cytokines, suppression or killing of effector T cells or bringing the APC into tolerogenic state. HSP induced Tregs play an important role in combating autoimmunity and inflammation. CONCLUSION Present review gives an insight towards the cause of inflammation and an account of different HSPs contributing various inflammatory disorders viz. inflammatory bowel disease (IBD), intestinal inflammation, atherosclerosis, rheumatoid arthritis (RA), multiple sclerosis etc. The importance of HSPs in handling inflammatory disorders has been depicted in recent patents also.

Ebola virus – epidemiology, diagnosis, and control: threat to humans, lessons learnt, and preparedness plans – an update on its 40 year's journey

ABSTRACT Ebola virus (EBOV) is an extremely contagious pathogen and causes lethal hemorrhagic fever disease in man and animals. The recently occurred Ebola virus disease (EVD) outbreaks in the West African countries have categorized it as an international health concern. For the virus maintenance and transmission, the non-human primates and reservoir hosts like fruit bats have played a vital role. For curbing the disease timely, we need effective therapeutics/prophylactics, however, in the absence of any approved vaccine, timely diagnosis and monitoring of EBOV remains of utmost importance. The technologically advanced vaccines like a viral-vectored vaccine, DNA vaccine and virus-like particles are underway for testing against EBOV. In the absence of any effective control measure, the adaptation of high standards of biosecurity measures, strict sanitary and hygienic practices, strengthening of surveillance and monitoring systems, imposing appropriate quarantine checks and vigilance on trade, transport, and movement of visitors from EVD endemic countries remains the answer of choice for tackling the EBOV spread. Herein, we converse with the current scenario of EBOV giving due emphasis on animal and veterinary perspectives along with advances in diagnosis and control strategies to be adopted, lessons learned from the recent outbreaks and the global preparedness plans. To retrieve the evolutionary information, we have analyzed a total of 56 genome sequences of various EBOV species submitted between 1976 and 2016 in public databases.

Beneficial health applications and medicinal values of Pedicularis plants: A review

Pedicularis plants (Orobanchaceae), popularly known as lousewort, are found in Asia, Europe, and North America, and have been used in Sowa-Rigpa, the Himalayan art of healing and a traditional system of medicine for treating various ailments in humans. A comprehensive compilation on this valuable medicinal plant is not available, however. The present extensive review provides insight into the salient medicinal properties of Pedicularis plants with respect to various health issues and diseases. Our previous studies on Pedicularis plants from the Changthang region of Ladakh (India) and research advances leading to new developments in this field have prompted this review. The information presented here has been compiled and analyzed from authenticated published resources available on Medline, Pubmed, Pubmed Central, Science Direct, and other scientific databases. The Pedicularis genus consists of approximately 600 species (83 of which are found in India), with commonly reported species being Pedicularis longiflora Rudolph, P. bicornuta Klotzsch, P. oederi Vahl, P. cheilanthifolia, and P. pectinata. The major phytoconstituents of the Pedicularis sp. are phenols, phenylethanoids, phenylpropanoids, flavonoids, iridoids, lignans, and alkaloids, among others. The existing literature highlights that these compounds possess antioxidant, immunomodulatory, anti-inflammatory, antidiabetic, antibacterial, antifungal, analgesic, antitumor, hepatoprotective, neuroprotective, muscle-relaxing, antifatigue, diuretic, antipyretic, antithrombus, antihemolysis, and DNA-repairing properties. This medicinal herb is used in the treatment of leucorrhoea, fevers, sterility, rheumatism, general debility, collapse, and urinary problems, and for revitalizing the blood circulation, improving digestion, and maintaining vitality. This review emphasizes the various medicinal aspects of Pedicularis sp. plants containing a variety of phytoconstituents. Besides phenols, terpenoids, flavonoids, lignans, tannins, iridoid, and phenylpropanoid glycosides are among the active constituents responsible for multiple health effects. However, further extensive research is required to characterize the various phytoconstituents of Pedicularis to explore their modes of action at a molecular level and identify other beneficial applications that can exploit the tremendous medicinal potential of this important herb.

Medicinal and Therapeutic Potential of Herbs and Plant Metabolites / Extracts Countering Viral Pathogens - Current Knowledge and Future Prospects

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.

Probiotics in Curing Allergic and Inflammatory Conditions - Research Progress and Futuristic Vision

BACKGROUND Probiotics constitute the viable and beneficial microbes, which offer a dietary means to sustain the balance of gastro-intestinal (GI) microflora. Owing to their multiple health benefits, these have recently gained wide attention among researchers for exploring their potential in safeguarding the health of humans and animals. Probiotics could also modulate host-immune responses, thereby help in counteracting the immunological dysfunctions. Probiotics can inhibit the systemic invasion of pathogens entering through the GI mucosa/ oral cavity and have been found to possess effective prophylactic and therapeutic utilities against various infectious pathogens as well as non-infectious diseases and disorders. OBJECTIVE The present review expedites the role of probiotics in curing the ailments related to allergic and inflammatory disease conditions. METHOD A thorough reviewing of the literature and patents available on probiotics and their role in countering inflammation and allergy was conducted using authentic published resources available on Medline, PubMed, PubMed Central, Science Direct and other scientific databases. The information retrieved has been compiled and analysed pertaining to the theme of the study. RESULTS Various micro-organisms have been evaluated for their probiotic efficacy, among these, the lactic acid bacteria viz. Lactobacillus sp. and Bifidobacterium sp. have extensively been studied and widely exploited. In the current post-globalized era of self and complementary medicines, the concept of probiotics and their therapeutic as well as prophylactic usage is gaining wide acceptance. As more and more bacterial strains are being proven for their pronounced influence on down regulation of immune regulation, atopic, inflammatory conditions, the use of probiotics is getting increased especially in the developed countries where such indications are high in prevalence. Apart from usage in immune related disorders, probiotics have been found to be effective in treating pouchitis, infantile diarrhoea due to infections, bacterial vaginosis, urinary tract infections, dental carries, diabetes, cancers as well augmenting the gut mucosal tolerance to various antibiotics and lactose intolerance. CONCLUSION The resent review gives an insight towards potent utility of this branch of beneficial microbial therapy in allergy and inflammations, which is still in the emerging phase and more scientific evidences need to be explored regarding exploration of the mechanisms of action, further experimental trials and validation of controlled clinical studies in humans along with designing novel strategies for monitoring the possible microbial changes in their composition and metabolism associated with their interaction upon host immune system.

Physiology and biochemistry of aluminum toxicity and tolerance in crops

Achieving sustainable food production to feed the increasing population of the problematic lands of the world is an enormous challenge. Aluminum (Al) toxicity in the acid soil is a major worldwide problem. Liming and nutrient management technologies are worthless due to high lime requirement, and the effect of liming does not persist for long. Besides this, conventional breeding is useful to manage Al toxicity as some plants have evolved mechanisms to cope with Al toxicity in acid soil. Therefore, understanding of Al tolerance mechanisms is prime necessity for improving Al tolerance in crops. Al resistance mechanisms include mainly Al avoidance (Al exclusion) and/or Al tolerance (detoxification of Al inside the cell) mechanisms. In this chapter, we summarize Al behavior in plant root cell. We include recent findings of Al resistance mechanisms and Al-resistant genes which can be useful to produce cultivars adapted to acid soils.