Plausible mechanism of drug resistance and side-effects of COVID-19 therapeutics: a bottleneck for its eradication.

Background: COVID-19 pandemic has turned our world upside down by meddling with our normal lives. While there is no definitive drug against SARS-CoV-2, antiviral drugs that are already in the market, are being repurposed against it, could now complete long-term as well as all age-specific investigations, and they are successful in saving millions of lives. Nevertheless, side-effects are emergingly seen in the patients undergoing treatment, and ineffectiveness is increasingly found due to the emerging notorious variants of the virus.

Engineering immune response to regulate cardiovascular disease and cancer.

Cardiovascular disease (CVD) and cancer are major contributors to global morbidity and mortality. This book chapter delves into the intricate relationship between the immune system and the pathogenesis of both cardiovascular and cancer diseases, exploring the roles of innate and adaptive immunities, immune regulation, and immunotherapy in these complex conditions. The innate immune system acts as the first line of defense against tissue damage and infection, with a significant impact on the initiation and progression of CVD and cancer.

Translational bioinformatics approach to combat cardiovascular disease and cancers.

Bioinformatics is an interconnected subject of science dealing with diverse fields including biology, chemistry, physics, statistics, mathematics, and computer science as the key fields to answer complicated physiological problems. Key intention of bioinformatics is to store, analyze, organize, and retrieve essential information about genome, proteome, transcriptome, metabolome, as well as organisms to investigate the biological system along with its dynamics, if any. The outcome of bioinformatics depends on the type, quantity, and quality of the raw data provided and the algorithm employed to analyze the same.

Implications of vitamin D deficiency in systemic inflammation and cardiovascular health.

Clinical, epidemiological, and molecular studies have sufficiently highlighted the vitality of vitamin D [25(OH)D and 1,25(OH)D] in human health and wellbeing. Globally, vitamin D deficiency (VDD) has become a public health concern among all age groups. There is a very high prevalence of VDD per the estimates from several epidemiological studies on different ethnic populations.

Oncogenic role of an uncharacterized cold-induced zinc finger protein 726 in breast cancer.

The unobtrusive cold environmental temperature can be linked to the development of cancer. This study, for the first time, envisaged cold stress-mediated induction of a zinc finger protein 726 (ZNF726) in breast cancer. However, the role of ZNF726 in tumorigenesis has not been defined.

Biochemical and structural insights into SARS-CoV-2 polyprotein processing by Mpro.

SARS-CoV-2, a human coronavirus, is the causative agent of the COVID-19 pandemic. Its genome is translated into two large polyproteins subsequently cleaved by viral papain-like protease and main protease (Mpro). Polyprotein processing is essential yet incompletely understood.

Altered neural cell junctions and ion-channels leading to disrupted neuron communication in Parkinson's disease.

Parkinson's disease (PD) is a neurological disorder that affects the movement of the human body. It is primarily characterized by reduced dopamine levels in the brain. The causative agent of PD is still unclear but it is generally accepted that α-synuclein has a central role to play.

Metronidazole, acyclovir and tetrahydrobiopterin may be promising to treat COVID-19 patients, through interaction with interleukin-12.

COVID-19 patients have shown overexpressed serum levels of several pro-inflammatory cytokines, leading to a high mortality rate due to numerous complications. Also, previous studies demonstrated that the metronidazole (MTZ) administration reduced pro-inflammatory cytokines and improved the treatment outcomes for inflammatory disorders. However, the effect and mechanism of action of MTZ on cytokines have not been studied yet.

"Corrigendum to Herbs and their bioactive ingredients in cardio-protection: Underlying molecular mechanisms and evidences from clinical studies".

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Suramin, penciclovir, and anidulafungin exhibit potential in the treatment of COVID-19 via binding to nsp12 of SARS-CoV-2.

COVID-19, for which no confirmed therapeutic agents are available, has claimed over 48,14,000 lives globally. A feasible and quicker method to resolve this problem may be 'drug repositioning'. We investigated selected FDA and WHO-EML approved drugs based on their previously promising potential as antivirals, antibacterials or antifungals.

Herbs and their bioactive ingredients in cardio-protection: Underlying molecular mechanisms and evidences from clinical studies.

Background: Medicinal plants or herbs produce a bounty of bioactive phytochemicals. These phytochemicals can influence a variety of physiological events related to cardiovascular health through multiple underlying mechanisms, such as their role as antioxidative, anti-ischemic, anti-proliferative, hypotensive, anti-thrombotic, and anti-hypercholesterolemic agents.

Purpose: The purpose of this review is to summarize and connect evidences supporting the use of phytotherapy in the management of some of the most common cardiovascular impairments, molecular mechanisms underlying cardio-protection mediated by herbs, and clinical studies which are positively linked with the use of herbs in cardiovascular biology.

Comparative analysis of SARS-CoV-2 envelope viroporin mutations from COVID-19 deceased and surviving patients revealed implications on its ion-channel activities and correlation with patient mortality.

One major obstacle in designing a successful therapeutic regimen to combat COVID-19 pandemic is the frequent occurrence of mutations in the SARS-CoV-2 resulting in patient to patient variations. Out of the four structural proteins of SARS-CoV-2 namely, spike, envelope, nucleocapsid and membrane, envelope protein governs the virus pathogenicity and induction of acute-respiratory-distress-syndrome which is the major cause of death in COVID-19 patients. These effects are facilitated by the viroporin (ion-channel) like activities of the envelope protein.

Revealing the Structural Plasticity of SARS-CoV-2 nsp7 and nsp8 Using Structural Proteomics.

Coronavirus (CoV) nonstructural proteins (nsps) assemble to form the replication-transcription complex (RTC) responsible for viral RNA synthesis. nsp7 and nsp8 are important cofactors of the RTC, as they interact and regulate the activity of RNA-dependent RNA polymerase and other nsps. To date, no structure of the full-length SARS-CoV-2 nsp7:nsp8 complex has been published.

Resolving the Dynamic Motions of SARS-CoV-2 nsp7 and nsp8 Proteins Using Structural Proteomics.

Coronavirus (CoV) non-structural proteins (nsps) assemble to form the replication-transcription complex (RTC) responsible for viral RNA synthesis. nsp7 and nsp8 are important cofactors of the RTC, as they interact and regulate the activity of RNA-dependent RNA polymerase (RdRp) and other nsps. To date, no structure of full-length SARS-CoV-2 nsp7:nsp8 complex has been published.

Functional implications of vascular endothelium in regulation of endothelial nitric oxide synthesis to control blood pressure and cardiac functions.

The endothelium is the innermost vascular lining performing significant roles all over the human body while maintaining the blood pressure at physiological levels. Malfunction of endothelium is thus recognized as a biomarker linked with many vascular diseases including but not limited to atherosclerosis, hypertension and thrombosis. Alternatively, prevention of endothelial malfunctioning or regulating the functions of its associated physiological partners like endothelial nitric oxide synthase can prevent the associated vascular disorders which account for the highest death toll worldwide.

Dopamine β hydroxylase as a potential drug target to combat hypertension.

Introduction: Despite a large number of commercially available drugs, hypertension and related cardiovascular diseases remain a global problem. It is thus imperative that novel drugs and therapeutic strategies are regularly identified, and alternative targets explored. Dopamine β hydroxylase (DBH), a key player in the catecholamine biosynthetic pathway, may provide a therapeutic opportunity and should be extensively explored as a target for potent anti-hypertensives.

Experimental oral iron administration: Histological investigations and expressions of iron handling proteins in rat retina with aging.

Iron is implicated in age-related macular degeneration (AMD). The aim of this study was to see if long-term, experimental iron administration with aging modifies retinal and choroidal structures and expressions of iron handling proteins, to understand some aspects of iron homeostasis. Male Wistar rats were fed with ferrous sulphate heptahydrate (500mg/kg body weight/week, oral; elemental iron availability: 20%) from 2 months of age onward until they were 19.

Characterization of SNPs in the dopamine-β-hydroxylase gene providing new insights into its structure-function relationship.

Dopamine-β-hydroxylase (DBH, EC 1.14.17.

Assessment of amsacrine binding with DNA using UV-visible, circular dichroism and Raman spectroscopic techniques.

Proper understanding of the mechanism of binding of drugs to their targets in cell is a fundamental requirement to develop new drug therapy regimen. Amsacrine is a rationally designed anticancer drug, used to treat leukemia and lymphoma. Binding with cellular DNA is a crucial step in its mechanism of cytotoxicity.

Lysine richness in human snurps - possible sites for electrophilic attacks.

Gene-expression strategies are remodeled following exposure to stress. The reactive oxidants and electrophiles generated after stress actually affects the structural and functional properties of different cellular proteins. It is also seen that lysine rich motifs of proteins play crucial role in electrophilic attack and modification.