Current Pharmaceutical Design - Volume 26, Issue 41, 2020

The latest SARS COV2 coronavirus contributes to a pandemic of millions of COVID-19. As there is no defensive immunity in humans and a virus can overcome inborn immune reaction, it can propagate unhindered, mostly in tissues contaminated. No unique therapies for COVID-19 contaminated patients are available at this time. The insights learned from previous respiratory viral infection control have given guidance into COVID- 19 therapy. Several complementary treatments have been tentatively introduced in hospital environments such as immune-modulators, antiviral, convalescent plasma transfusions and natural products. In COVID-19 patients, some of these therapies have provided substantial curative benefits. Moreover, numerous studies and clinical trials are being carried out in order to determine the efficacy of current pharmaceutical and natural products to establish possible therapeutic strategies for producing novel COVID-19 medicines. We summarized and defined the modes of mechanism, protection and efficacy on the existing therapeutic strategies for diseases linked to COVID-19 infection.

Background: SARS-CoV-2 is a coronavirus, and the infection by SARS-CoV-2, termed as COVID-19, was first reported in Wuhan, China, at the end of 2019, and this outbreak became a pandemic in February of 2020. Till now, there is no effective drug or vaccine against this virus that can make a complete cure; however, a number of drugs are in trials. Objectives: In this review, we have focused on an alternative therapeutic approach using natural products utilizing the host anti-viral responses for resolving COVID-19 pathogenesis. Methods: We have searched databases like PubMed, Scopus, Web of Science, and Google Scholar for articles related to natural products and viral diseases, with a specific focus on coronaviruses, as well as other RNA viruses and recent updates on the COVID-19 pandemic, and collected articles and reviewed them comprehensively. Results: Scientific studies clarified the viral pathogenesis that involved viral entrance into host cells and anti-viral response inside the cells, which can be effectively targeted by numerous natural compounds from different sources. Many of these compounds can potentially target viral genomic material or protein machinery. Natural products that were found effective against other coronaviruses, especially SARS-CoV or MERS-CoV (which emerged in 2002 and 2012, respectively), might be effective against SARS-CoV-2 due to their structural similarities. Conclusion: COVID-19 pandemic is a global emergency thus, urgent drug development is necessary. Natural products can be the biggest source of drugs, as they have been found to be effective in other coronaviruses previously; however, time is required to establish the clinical success of these drugs for clinical applications.

On 11th March 2020, the World Health Organisation (WHO) announced a pandemic caused by a novel beta-coronavirus SARS-CoV-2, designated COVID-19. The virus emerged in December 2019 in Wuhan, China, has spread across the world as a global pandemic. The traditional use of medicines from plants can be traced back to 60,000 years. Global interest in the development of drugs from natural products has increased greatly during the last few decades. Essential oils (EOs) have been studied through the centuries and are known to possess various pharmaceutical properties. In the present review, we have highlighted the current biology, epidemiology, various clinical aspects, different diagnostic techniques, clinical symptoms, and management of COVID-19. An overview of the antiviral action of EOs, along with their proposed mechanism of action and in silico studies conducted, is described. The reported studies of EOs' antiviral activity highlight the baseline data about the additive and/or synergistic effects among primary or secondary phytoconstituents found in individual oils, combinations or blends of oils and between EOs and antiviral drugs. It is hoped that further research will provide better insights into EOs' potential to limit viral infection and aid in providing solutions through natural, therapeutically active agents.

Background: Coronavirus disease 2019 (COVID-19) is an ongoing, rapidly spreading pandemic caused by Severe Acute Respiratory Syndrome Coronavirus2 (SARS-CoV2). Among all the infected countries around the globe as of now (June 15, 2020), the total confirmed positive cases reported are 7,805,148, with the death of 431,192. At present, no specialized treatments evolved to cure COVID-19. Its treatment is symptomatic. Though huge efforts are being made to produce potential therapies to scuffle COVID-19, no drug has been discovered so far. Objective: Natural products have been playing a significant role in disease control since ancient days. These products serve as templates for designing new anti-microbial agents with a different mechanism of action and also open a door for investigation of effective anti-viral drugs to combat COVID-19. By focusing on this, the authors have narrated the basic structure, infection, and pathogenesis of SARS-CoV2 virus in humans and also reported various natural products or plant-based extracts/bioactive compounds tested against coronaviruses like SARS and MERS, as these viruses are structurally similar to SARS-CoV2 and can be used in designing novel drug against this virus. Conclusion: The natural products having the potential to combat SARS, MERS, and other viruses reviewed in this review article might have anti-viral activities against the SARS-CoV2 virus and can be used directly for further preclinical studies. Therefore, all efforts should be focused on overcoming this serious problem to save many people's lives all over the world.

Background: Human coronaviruses (HCoV) are common viruses and known to be associated with respiratory diseases, including pneumonia. Currently, seven human coronaviruses have been identified and known to cause upper and lower respiratory infections as well as nosocomial viral infections in humans. The bats, palm civets, and camels are identified as the reservoir of human coronaviruses. In 2002-2003, the emergence of SARS-CoV resulted in an outbreak and led towards the more awareness and importance of scientific research and medical urgency. Methods: The recently identified SARS-CoV-2 was identified from the seafood market of the city Wuhan, China, in December 2019 and caused a global pandemic. This virus has now spread to more than 213 countries. This is the third highly pathogenic human coronavirus after SARS and MERS-CoV. The coronaviruses have RNA as genetic material and are known to have frequent recombination and mutations in their genome, which lead to the emergence and re-emergence of new virus strains and isolates with novel properties and extended hosts. The genetic mutations and suitable environmental conditions result in the emergence and re-emergence of pathogenic coronaviruses and cause a serious issue to human health and the economy globally. Lectins are the ubiquitous group of proteins that bind to glycosylated molecules. Conclusion: The plant lectins are known to have significant antiviral activities against coronaviruses. Additionally, the plant lectins can be used as potential therapeutics against bacteria, fungus, yeast, and protozoa. In this review, we have discussed the current status of human pathogenic coronavirus emergence and the use of plant lectins as antivirals against SARS-CoV-2.

Background: Dengue virus is a potential source of propagating dengue hemorrhagic fever. This virus leads to dengue hemorrhagic fever/dengue shock syndrome, benign syndrome, and severe syndrome and due to its infection, there occurs alterations at multiple levels such as gene expression and pathway levels. So, it is critical to understand the pathogenesis of dengue infection in terms of gene expression and the associated functions. Methods: For this purpose, here, we have analyzed the temporal gene expression profiling for the dengue hemorrhagic fever dataset at 12, 24, and 48 hours. Results: The outcome appears that the dengue hemorrhagic fever evolves differently at different time periods or stages. Conclusion: The change in the gene expression pattern increases exponentially from 12 hours to 48 hours and the number of altered functions (pathways) also increases. Wnt, apoptosis, and transcription signaling are among the critical pathways which are dominantly altered. In the initial phase (first 12 hours), only two pathways are altered due to dengue infection, while in the next 12 hours, eight pathways are altered, and finally, in the next 24 hours, 11 pathways are altered and most of these 11 pathways are very critical in terms of biological pathways and functions.

Background: Previously human society has faced various unprecedented pandemics in the history and viruses have majorly held the responsibilities of those outbreaks. Furthermore, due to amplified global connection and speedy modernization, epidemic outbreaks caused by novel and re-emerging viruses signify potential risk to community health. Despite great advancements in immunization and drug discovery processes, various viruses still lack prophylactic vaccines and efficient antiviral therapies. Although, vaccine is a prophylaxes option, but it cannot be applied to infected patients, hence therapeutic interventions are urgently needed to control the ongoing global SARS- CoV-2 pandemic condition. To spot the novel antiviral therapy is of decisive importance and Mother Nature is an excellent source for such discoveries. Methodology: In this article, prompt high through-put virtual screening for vetting the best possible drug candidates from natural compounds’ databases has been implemented. Herein, time tested rigorous multi-layered drug screening process to narrow down 66,969 natural compounds for the identification of potential lead(s) is implemented. Druggability parameters, different docking approaches and neutralization tendency of the natural products were employed in this study to screen the best possible natural compounds from the digital libraries. Conclusion: The results of this study conclude that compounds PALA and HMCA are potential inhibitors of SARS-CoV-2 spike protein and can be further explored for experimental validation. Overall, the methodological approach reported in this article can be suitably used to find the potential drug candidates against SARS-CoV2 in the burning situation of COVID-19 with less expenditure and a concise span of time.

A steady and continuous supply of oxygen is important for humans, since an excess or deficiency in oxygen levels may result in the death of cells, tissues, or organisms. As a mechanical barrier against pathogens, the respiratory epithelium is always exposed to hypoxia in some detrimental external environments and/or pathologic states. The barrier function is accordingly impaired as a result of the disrupted cell composition ratio, ion transport, and tight junctions in a hypoxia-inducible factor-dependent or independent way. Hypoxia has been identified as an element of the primary or secondary pathogenic factors of many respiratory diseases. Still, the relationship between hypoxia and epithelial barrier dysfunction is not fully understood. Thus, we summarized recent researches on epithelial barrier dysfunction induced by hypoxia in the respiratory system, aiming to explore the possible therapeutic targets in hypoxia-related respiratory system diseases.

Background: There is a clear clinical need for a better understanding of the biological underpinnings of major depressive disorder (MDD), allowing for the development of a treatment that is targeted to pathophysiology. Recent data indicate a role for the endogenous opioidergic system in MDD. This article reviews the roles and physiological interactions of the endogenous opioidergic system in the pathophysiology and heterogeneity of MDD. Methods: Articles on the pathophysiology of MDD, as well as on the endogenous opioidergic system and mitochondrial function, form the basis of this review article. Results: The endogenous opioidergic system is intimately linked to wider MDD pathophysiology, including alterations in the gut microbiome, gut permeability, circadian rhythm, amygdala-prefrontal cortex interactions, and mitochondrial function. A decrease in the μ-/Κ-opioid receptor ratio is an important mediator of the changes in mood in MDD, with effects not only on neurons, but also on glia and immune cells. Conclusion: The endogenous opioidergic system is intimately interwoven with MDD pathophysiology and provides a relevant target for novel treatment development, as well as providing a focus for the integration of wider MDD pathophysiology.

Background: In view of the roles of long non-coding RNA CDKN2B antisense RNA 1 (CDKN2BAS1) in various human diseases, we investigated the function of CDKN2B-AS1 and explored its therapeutic and prognostic target value in multiple biological processes. The aim of this review was to explore the molecular mechanism and clinical significance of CDKN2B-AS1 in various types of diseases. Materials and Methods: In this review, the biological functions and mechanisms of lncRNA CDKN2B-AS1 in a variety of pathophysiological processes were summarized and analyzed. The correlated studies were collected via a systematic search of PubMed, Wiley Online Library, and ScienceDirect. Results: CDKN2B-AS1 is a potential long non-coding RNA that has been shown to be aberrantly expressed in various malignancies, containing hepatocellular carcinoma, intrahepatic cholangiocarcinoma, esophageal squamous cell carcinoma, gastric cancer, colonic adenocarcinoma, cervical cancer, ovarian cancer, breast cancer, glioma, lung cancer, laryngeal squamous cell carcinoma and osteosarcoma, involving in the processes of tumor cells proliferation, migration, invasion and inhibition of tumor cells apoptosis. Besides, CDKN2B-AS1 has been proved implicated in numerous non-malignant diseases, such as idiopathic pulmonary fibrosis, endometriosis, inflammatory bowel disease, intracranial aneurysm, diabetes mellitus and its complications, primary open angle glaucoma, ischemic stroke, atherosclerosis, coronary artery diseases, hypertension and heart failure, participating in the procession of lipid, carbohydrate metabolism and inflammation regulation. Conclusion: Long non-coding RNA CDKN2B-AS1 likely serves as a promising therapeutic target or prognosis biomarker in multiple human diseases.

γ-Poly-glutamic acid (γ-PGA) is a naturally occurring homo-polyamide produced by various strains of Bacillus. As a biopolymer substance, γ-PGA possesses a few predominant features containing good water solubility, biocompatibility, degradability and non-toxicity. Based on this, γ-PGA can be used in pharmaceutical, such as drug carrier/deliverer, vaccine adjuvant, and coating material for microencapsulation, etc. Moreover, it has also been applied in a broad range of industrial fields including food, medicine, bioremediation, cosmetics, and agriculture. Especially, γ-PGA is an extremely promising food ingredient. In this mini-review, our aim is to review the function and application progress of γ-PGA in the food industry: e.g., improving taste and flavor, enhancing physical property, and promoting health.

Background: The progressive treatment of cancer using disulfide bond-based therapeutics offers improvement in therapeutic potency of active, reduction in adverse events, prolongation of drug release pattern and on-site action by interacting with neoplastic cell microenvironment. Objective: The objective of this article is to highlight the research carried out on disulfide bond-based drug delivery systems as a potential candidate for cancer treatment. Methods: The article provides an overview of the importance of disulfide bonds in cancer treatment in terms of their properties, mechanism of formation/fragmentation and applications. Properties of disulfide bonds, such as pKa, entropy, and dihedral angle contribute to the structural stability of the bonds in a nanotherapeutic system, while their formation and fragmentation are attributed to the presence of a high concentration of GSH in cancer cells. The article further focuses on various drug delivery systems like dendrimers, liposomes, micelles, etc. involving disulfide cross-linked polymers for the preparation of redox-responsive drug delivery systems. Results: The use of nanotechnology with disulfide bond creates an anticancer drug delivery system with higher target specificity, improved bioavailability, and good therapeutic efficacy. Conclusion: In the near future, the combination of DSB with active, cellular material, stem cell and biological fluid will be considered as a new thrust area for research in healthcare.

Due to an overlook, publication type in the article entitled as "Bisphosphonates Can Maintain Periprosthetic Bone Mass Density after Total Hip Replacement, with Controversy in Region of Interest 5" by Dr. Dongsheng Hao published in the journal "Current Pharmaceutical Design" Volume 26, No 38, Page no. 4925-4933 was wrong. The corrected publication type is Research Article. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy can be found at https://benthamscience.com/editorial-policies-main.php Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.