Targeting Omicron (B.1.1.529) SARS CoV-2 spike protein with selected phytochemicals: an in-silico approach for identification of potential drug

Severe acute respiratory syndrome coronavirus -2 (S ARS-CoV-2) emerging variants particularly those of concern contain numerous mutations that influence the behavior and transmissibility of the virus and could adversely affect the efficacies of existing coronavirus disease 2019 (COVID-19) vaccines and immunotherapies. The emerging SARS-CoV-2 variants have resulted in different waves of the pandemic within the ongoing COVID-19 pandemic. On 26 November 2021 World Health Organization designated omicron (B.1.1.529) as the fifth variant of concern which was first reported from South Africa on November 24, 2021, and thereafter rapidly spread across the globe owing to its very high transmission rates along with impeding efficacies of existing vaccines and immunotherapies. Omicron contains more than 50 mutations with many mutations (26-32) in spike protein that might be associated with high transmissibility. Natural compounds particularly phytochemicals have been used since ancient times for the treatment of different diseases, and owing to their potent anti-viral properties have also been explored recently against COVID-19. In the present study, molecular docking of nine phytochemicals (Oleocanthal, Tangeritin, Coumarin, Malvidin, Glycitein, Piceatannol, Pinosylnin, Daidzein, and Naringenin) with omicron spike protein (7QNW (electron microscopy, resolution 2.40 Å) was done. The docking study revealed that selected ligands interact with the receptor with binding energy in the range of -6.2 to-7.0 kcal/mol. Pinosylnin showed the highest binding energy of -7.0 kcal/mol which may be used as potential ligands against omicron spike protein. Based on the docking studies, it was suggested that these phytochemicals are potential molecules to be tested against omicron SARS-CoV-2 and can be used to develop effective antiviral drugs

In silico targeting of osmoporin protein of Salmonella to identify anti-Salmonellosis phyto-compounds

Salmonella enterica serotype typhi is a gram-negative, rod-shaped bacterium, and has flagella with the human body as its only reservoir. Typhoid fever was found to cause 21.7 million illnesses and 216,000 fatalities worldwide in 2000, and the International Vaccine Institute estimated 11.9 million cases and 129,000 deaths in low- and middle-income countries in 2010. More than 10 million patients were infected with S. typhi each year and the mortality rate is associated with more than 0.1 million patients. Moreover, it is also associated with drug resistance globally which makes the disease more dreadful. Other than antibiotics, various flavonoids showed medicinal effects against many diseases including S. typhi infection. Flavonoids are a type of plant bioactive metabolite that have potential medicinal efficacy. The goal of this study was to see if certain flavonoids (ellagic acid, eriodictyol, and naringenin) could interact with the outer membrane of osmoporin (PDB ID: 3uu2) receptor in Salmonella and helps in inhibiting its growth. To look for probable ligand-receptor binding relationships, we used Pyrxmolecular docking software. The molecular docking results were analyzed using the Biovia discovery studio visualizer. The current study discovered that selected plant-based compounds interacted with an outer membrane of the osmoporin receptor, resulting in minimization of energy in the range of-6.6 to -7.8 Kcal/mol

In Silico Targeting of influenza virus haemagglutinin receptor protein using Diosmetin, Tangeritin, and Anthocyanidins as potential drugs

Influenza viruses cause acute respiratory illnesses in birds, humans, and other mammals, and are a major public health concern around the world. Pandemic flu could be caused by an unforeseen human adaptation of an influenza subtype or strain rather than currently circulating influenza viruses. The need for plant metabolites-based new anti-influenza drugs appears to be urgent. Blocking Haemeagglutinin (HA) protein is one of the most appealing drug targets to halt the growth of the virus. The influenza virus can acquire resistance to currently existing therapies, therefore necessitating the development of new medications. The plant's bioactive metabolites, flavanoids are having potential medicinal efficacy. The current study aimed to identify certain flavonoids (Diosmetin, Tangeritin, and Anthocyanidins) that might interact with the HA protein of the influenza virus and help in inhibiting its growth. We used PyRx v0.8 for virtual screening and docking studies. The highest binding affinity docked structures were analyzed using PyMOL and Discovery Studio Visualizer. The present study revealed that these naturally occurring compounds interacted with HA protein, resulting in the minimization of energy in the range of -5.2 to -7.0 kcal/mol. Diosmetin showed the best binding affinity of -7.0Kcal/mol. The molecular binding studies revealed that Diosmetin, Tangeritin, and Anthocyanidins are potential compounds to test against HA protein and can be used to develop effective anti-influenza agents

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Therapeutic Potential of Polymer-Coated Mesoporous Silica Nanoparticles

Mesoporous silica nanoparticles (MSNs) find tremendous applications in drug delivery due to several advantages such as their easy fabrication process, high drug loading, biodegradability, biocompatibility, and so forth. Nevertheless, despite several advantages, the use of this striking drug delivery carrier is restricted due to premature drug release owing to the porous structure. Coating of the pores using polymers has emerged as a great solution to this problem. Polymer coatings, which act as gatekeepers, avoid the premature release of loaded content from MSNs and offers the opportunity for controlled and targeted drug delivery. Therefore, in this review, we have compiled the polymer-based coating approaches used in recent years for improving the drug delivery capability of MSNs. This manuscript provides an insight into the research about the potential of polymer-coated MSNs, allowing the selection of right polymer for coating purposes according to the desired application

Renewable poly(δ-decalactone) based block copolymer micelles as drug delivery vehicle: in vitro and in vivo evaluation

Polymers from natural resources are attracting much attention in various fields including drug delivery as green alternatives to fossil fuel based polymers. In this quest, novel block copolymers based on renewable poly(δ-decalactone) (PDL) were evaluated for their drug delivery capabilities and compared with a fossil fuel based polymer i.e. methoxy-poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-b-PCL). Using curcumin as a hydrophobic drug model, micelles of PDL block copolymers with different orientation i.e. AB (mPEG-b-PDL), ABA (PDL-b-PEG-b-PDL), ABC (mPEG-b-PDL-b-poly(pentadecalactone) and (mPEG-b-PCL) were prepared by nanoprecipitation method. The size, drug loading and curcumin stability studies results indicated that mPEG-b-PDL micelles was comparable to its counterpart mPEG-b-PCL micelles towards improved delivery of curcumin. Therefore, mixed micelles using these two copolymers were also evaluated to see any change in size, loading and drug release. Drug release studies proposed that sustained release can be obtained using poly(pentadecalactone) as crystalline core whereas rapid release can be achieved using amorphous PDL core. Further, mPEG-b-PDL micelles were found to be non-haemolytic, up to the concentration of 40 mg/mL. In vivo toxicity studies on rats advised low-toxic behaviour of these micelles up to 400 mg/kg dose, as evident by histopathological and biochemical analysis. In summary, it is anticipated that mPEG-b-PDL block copolymer micelles could serve as a renewable alternative for mPEG-b-PCL copolymers in drug delivery applications

Polymer-Drug Conjugates as Nanotheranostic Agents

Since the last decade, the polymer-drug conjugate (PDC) approach has emerged as one of the most promising drug-delivery technologies owing to several benefits like circumventing premature drug release, offering controlled and targeted drug delivery, improving the stability, safety, and kinetics of conjugated drugs, and so forth. In recent years, PDC technology has advanced with the objective to further enhance the treatment outcomes by integrating nanotechnology and multifunctional characteristics into these systems. One such development is the ability of PDCs to act as theranostic agents, permitting simultaneous diagnosis and treatment options. Theranostic nanocarriers offer the opportunity to track the distribution of PDCs within the body and help to localize the diseased site. This characteristic is of particular interest, especially among those therapeutic approaches where external stimuli are supposed to be applied for abrupt drug release at the target site for localized delivery to avoid systemic side effects (e.g., Visudyne®). Thus, with the help of this review article, we are presenting the most recent updates in the domain of PDCs as nanotheranostic agents. Different methodologies utilized to design PDCs along with imaging characteristics and their applicability in a wide range of diseases, have been summarized in this article

Antiarthritic Activities of Herbal Isolates: A Comprehensive Review

Numerous plant isolates with therapeutic properties, such as antimicrobial, antiinflammatory, antiviral, antimalarial, antiarthritic (AA), hepatoprotective, cardiotonic, and so forth, are reported in the literature. Usually, medicinal plants are widely used, and assumed to be safe and cheaper alternatives to chemically synthesized drugs. However, they are not regulated for potency and purity, and thus care must be taken for their safe use. In this review, we aimed to compile all of the herbal isolates possessing AA properties, including alkaloids (montanine, 3-acetylaconitine, sanguinarine, jatrorrhizine hydrochloride, and piperine), terpenoids (eugenol, nimbolide, bartogenic acid, cannabidiol, and curcumin), and flavonoids (quercetin, resveratrol, kaempferol, chebulanin, ellagic acid, rosmarinic acid, gallic acid, chlorogenic acid, ferulic acid, and brazilin). These isolates act through numerous pharmacological mechanisms such as inhibiting cytokines, chemokines, or matrix metalloproteinase, etc., to demonstrate AA activity. Animal models utilized for assessing the AA properties of these isolates, including adjuvant-induced arthritis mouse models, are also discussed. Furthermore, nanotechnology-based approaches to deliver these isolates are also reviewed, which have shown improved therapeutic efficacy of isolated compounds

Green Nanotechnology: Advancement in Phytoformulation Research

The ultimate goal of any scientific development is to increase well-being and human health. Novel strategies are required for the achievement of safe and effective therapeutic treatments beyond the conventional ones, and society needs new requirements for new technologies, moving towards clean and green technology development. Green nanotechnology is a branch of green technology that utilizes the concepts of green chemistry and green engineering. It reduces the use of energy and fuel by using less material and renewable inputs wherever possible. Green nanotechnology, in phytoformulations, significantly contributes to environmental sustainability through the production of nanomaterials and nanoproducts, without causing harm to human health or the environment. The rationale behind the utilization of plants in nanoparticle formulations is that they are easily available and possess a broad variability of metabolites, such as vitamins, antioxidants, and nucleotides. For instance, gold (Au) nanoparticles have attracted substantial attention for their controllable size, shape, and surface properties. A variety of copper (Cu) and copper oxide (CuO) nanoparticles have also been synthesized from plant extracts. Titanium dioxide and zinc oxide nanoparticles are also important metal oxide nanomaterials that have been synthesized from a number of plant extracts. International and domestic laws, government and private-party programs, regulations and policies are being carefully reviewed and revised to increase their utility and nurture these nanoscale materials for commercialization. Inspiring debates and government initiatives are required to promote the sustainable use of nanoscale products. In this review, we will discuss the potential of the utilization of plant extracts in the advancement of nanotechnology