To evaluate the effect of endothelin receptor agonist IRL-1620 alone and in combination with donepezil in modulating neurodegeneration elicited by amyloid-ß in rats.

BACKGROUND: The development of efficient therapies for Alzheimer''s disease is essential since it is a serious public health problem. This investigation sought to ascertain any potential synergistic benefits of treating Alzheimer's disease with IRL-1620 monotherapy in addition to Donepezil. Additionally, the effect of IRL-1620 was evaluated using different doses (5 µg/kg,7 µg/kg, and 9 µg/kg). The study further assessed neurobehavioral, biochemical, molecular, and histopathological parameters to evaluate the efficacy of both IRL1620 by its own and in association with Donepezil. Fifty-eight adult male Wistar rats were allocated to eight experimental groups. A dose-ranging study of IRL-1620 was conducted using different doses administered via intravenous injection. Alzheimer's disease was induced by Aß administration, and treatment arms included disease Control (Sham), Donepezil monotherapy, and combination treatment with IRL-1620 5 µg/kg (Dose selected from the dose-ranging study). The treatment using IRL-1620 (9 µg/kg) intravenously and Donepezil (1 mg/kg orally) both on its own and in addition substantially enhanced memory in comparison with the control group (p < 0.05). Dose of IRL-1620 (9 µg/kg) intravenously, escape latency decreased and the time spent in the target quadrant was considerably increased, and they further benefited from combination therapy. Moreover, IRL-1620 (9 µg/kg) intravenously and combination treatment reduced lipid peroxidation and acetylcholinesterase levels while increasing antioxidant enzyme levels. Immunohistochemistry and molecular analysis revealed enhanced expression of neurotrophic factors with combination treatment. The combination of IRL-1620 and Donepezil showed significant improvements in memory and neurobehavioral parameters (p < 0.05). Alzheimer's disease in male Wistar rats. These results indicate to the probable therapeutic advantages of IRL-1620 and Donepezil in the management of Alzheimer's disease. The combination treatment exhibited enhanced effects compared to monotherapy, highlighting its potential promising therapeutic approach. Additional research is required to understand the mechanisms behind these synergistic benefits and to establish the ideal dosage and duration of therapy for therapeutic applications.

Effect of peanut stilbenoids, arachidin-1 and arachidin-3, on Streptococcus mutans growth and acid production.

In this study we evaluated the effect of prenylated peanut stilbenoids on the growth, biofilm accumulation and acid production of the dental caries pathogen Streptococcus mutans. Prior research with the non-prenylated stilbenes, resveratrol and piceatannol, has shown that these molecules are active against S. mutans. Here we sought to determine if the addition of a prenyl group to the stilbene backbone increased anti-S. mutans activities. Two prenylated stilbenes, arachidin-1 and arachidin-3, were produced using a peanut hairy root production system. Compared to resveratrol and piceatannol, both arachidin-1 and arachidin-3 led to greater inhibition of S. mutans planktonic growth. This effect also led to reduced biofilm formation, by inhibiting growth, instead of a specific action against biofilm cells. Lastly, sub-MIC concentrations of arachidin-3 reduced the acid production of S. mutans above the 'critical pH' that leads to tooth enamel erosion. In summary, stilbenoids have anti-S. mutans activity, and prenylation enhances this activity.

"Comparative evaluation of different chemical agents induced Autism Spectrum Disorder in experimental Wistar rats".

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition with uncertain etiology and pathophysiology. Several studies revealed that the commonly used animal models like Valproic Acid (VPA) and Propionic Acid (PPA) do not precisely represent the disease as the human patient does. The current study was conducted on different chemically (VPA, PPA, Poly I:C, Dioxin (2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)) & Chlorpyrifos (CPF)) induced ASD-like animal models and validated the best suitable experimental animal model, which would closely resemble with clinical features of the ASD. This validated model might help to explore the pathophysiology of ASD. This study included rat pups prenatally exposed to VPA, PPA, Poly I:C, Dioxin & CPF within GD9 to GD15 doses. The model groups were validated through developmental and behavioral parameters, Gene Expressions, Oxidative Stress, and Pro-inflammatory and Anti-inflammatory cytokines levels. Developmental and neurobehavioral parameters showed significant changes in model groups compared to the control. In oxidative stress parameters and neuro-inflammatory cytokines levels, model groups exhibited high oxidative stress and neuro-inflammation compared to control groups. Gene expression profile of ASD-related genes showed significant downregulation in model groups compared to the control group. Moreover, the Poly I:C group showed more significant results than other model groups. The comparison of available ASD-like experimental animal models showed that the Poly I:C induced model represented the exact pathophysiology of ASD as the human patient does. Poly I:C was reported in the maternal immune system activation via the inflammatory cytokines pathway, altering embryonic development and causing ASD in neonates.

A comprehensive insight on the challenges for COVID-19 vaccine: A lesson learnt from other viral vaccines.

The aim of this study is to comprehensively analyze previous viral vaccine programs and identify potential challenges and effective measures for the COVID-19 vaccine program. Previous viral vaccine programs, such as those for HIV, Zika, Influenza, Ebola, Dengue, SARS, and MERS, were evaluated. Paramount challenges were identified, including quasi-species, cross-reactivity, duration of immunity, revaccination, mutation, immunosenescence, and adverse events related to viral vaccines. Although a large population has been vaccinated, mutations in SARS-CoV-2 and adverse events related to vaccines pose significant challenges. Previous vaccine programs have taught us that predicting the final outcome of the current vaccine program for COVID-19 cannot be determined at a given state. Long-term follow-up studies are essential. Validated preclinical studies, long-term follow-up studies, alternative therapeutic approaches, and alternative vaccines are necessary.

Rat BM-MSCs secretome alone and in combination with stiripentol and ISRIB, ameliorated microglial activation and apoptosis in experimental stroke.

BACKGROUND: Stroke, a devastating neurological emergency, is the leading cause of worldwide mortality and functional disability. Combining novel neuroprotective drugs offers a way to improve the stroke intervention outcomes. In the present era, the combination therapy has been proposed as a plausible strategy to target multiple mechanisms and enhance the treatment efficacy to rescue stroke induced behavioral abnormalities and neuropathological damage. In the current study, we have investigated the neuroprotective effect of stiripentol (STP) and trans integrated stress response inhibitor (ISRIB) alone and in combination with rat bone marrow derived mesenchymal stem cells (BM-MSCs) secretome in an experimental model of stroke. MATERIALS & METHODS: Stroke was induced in male Wistar rats (n = 92) by temporary middle cerebral artery occlusion (MCAO). Three investigational agents were selected including STP (350 mg/kg; i.p.), trans ISRIB (2.5 mg/kg; i.p.) and rat BM-MSCs secretome (100 µg/kg; i.v). Treatment was administered at 3 hrs post MCAO, in four doses with a 12 hrs inter-dose interval. Post MCAO, neurological deficits, brain infarct, brain edema, BBB permeability, motor functional and memory deficits were assessed. Molecular parameters: oxidative stress, pro inflammatory cytokines, synaptic protein markers, apoptotic protein markers and histopathological damage were assessed. RESULTS: STP and trans ISRIB, alone and in combination with rat BM-MSCs secretome, significantly improved neurological, motor function and memory deficits along with significant reduction in pyknotic neurons in the brain of post MCAO rats. These results were correlating with significant reduction in pro-inflammatory cytokines, microglial activation and apoptotic markers in the brain of drug treated post MCAO rats. CONCLUSION: STP and trans ISRIB, alone and in combination with rat BM-MSCs secretome, might be considered as potential neuroprotective agents in the acute ischemic stroke (AIS) management.

Bulbiferamide, an Antitrypanosomal Hexapeptide Cyclized via an N-Acylindole Linkage from a Marine Obligate Microbulbifer.

UV absorption spectroscopy-guided fractionation of the culture extract of a marine obligate bacterium of the genus Microbulbifer yielded a novel cyclic hexapeptide, bulbiferamide (1). NMR spectroscopic and mass spectrometric analyses revealed the structure of 1 to be a cyclic tetrapeptide appending a ureido-bridged two amino acid unit. Notably, Trp is a junction residue, forming on one hand a very rare N-aminoacylated indole linkage for cyclization and on the other hand connecting the ureido-containing tail structure, which is an unprecedented way of configuring peptides. The component amino acids were determined to be l by the advanced Marfey's method. Compound 1 displayed growth inhibitory activity against Trypanosoma cruzi epimastigotes with an IC50 value of 4.1 µM, comparable to the currently approved drug benznidazole, while it was not cytotoxic to P388 murine leukemia cells at 100 µM.

PERK inhibitor, GSK2606414, ameliorates neuropathological damage, memory and motor functional impairments in cerebral ischemia via PERK/p-eIF2ɑ/ATF4/CHOP signaling.

The protein kinase R-like endoplasmic reticulum kinase/eukaryotic initiation factor 2ɑ (PERK/eIF2α), the branch of unfolded protein response (UPR), is responsible for transient arrest in translation to counter the enhanced levels of misfolded or unfolded proteins in the endoplasmic reticulum (ER) following any acute condition. In neurological disorders, overactivation of PERK-P/eIF2-P signaling, leads to a prolonged decline in global protein synthesis resulting in synaptic failure and neuronal death. Our study has shown, PERK/ATF4/CHOP pathway gets activated following cerebral ischemia in rats. We have further demonstrated, PERK inhibitor, GSK2606414 ameliorates ischemia induced neuronal damage by preventing additional neuronal loss, minimizing brain infarct, reducing brain edema, and preventing neurological symptoms from appearing. GSK2606414 was found to improve the neurobehavioral deficits and reduce the pyknotic neurons in ischemic rats. Also, it decreased glial activation and apoptotic protein mRNA expression while enhanced the synaptic protein mRNA expression in rat brain following cerebral ischemia. In conclusion, our findings suggest that PERK/ATF4/CHOP activation play a vital role in cerebral ischemia. Thus, PERK inhibitor, GSK2606414 might be a potential neuroprotective agent in cerebral ischemia.

Homotaurine ameliorates the core ASD symptomatology in VPA rats through GABAergic signaling: Role of GAD67.

Dysregulated GABAergic signaling is reported in Autism Spectrum disorder (ASD). In the present study, we evaluated a GABA structural mimicker homotaurine (HT) via in-silico docking and investigated the therapeutic efficacy of this drug to ameliorate ASD symptoms in the valproic acid (VPA) rat model of ASD. For the in-vivo study, animals were divided into two groups [Normal control (NC, 0.9 % saline; i.p) and disease control (VPA 600 mg/kg; i.p)] on gestational day (GD) 12.5. Male pups from VPA-exposed mothers were further divided into five groups (n = 6 in each group): disease control (DC, no-further treatment), standard treatment (risperidone (RES) 2.5 mg/kg; i.p, consecutively from PND 23-43), HT (10, 25 and 50 mg/kg; i.p, consecutively from PND 23-43). In in-silico studies, the binding pattern of homotaurine to GABA-A receptor was found similar to GABA with Tyr205, Glu155, Tyr157, Arg6, and Thr 130 as shared residues. In the in-vivo phase, the early developmental parameters (from PND 7-23) and behavioral parameters (from PND 43-54) were assessed. The offsprings of the VPA exposed group exhibited significant (p < 0.05) developmental delays, behavioral deficits [decreased sociability and social novelty (three-chamber sociability test), spatial memory (Morris water maze), increased stereotypy (self-grooming)], increased oxidative stress (decreased GSH, SOD, Catalase, and increased MDA), increased pro-inflammatory (IL-1ß, 6, TNF-α) and decreased anti-inflammatory (IL-10) cytokines, Purkinje cell loss in the cerebellum and pyknosis in PFC (H/E, Nissil staining) and decreased GAD67 expression in the cerebellum (RT-PCR & immunohistochemistry). Compared to the DC, HT treatment (50 mg/kg) was able to ameliorate the aberrant core behavioral deficits, decreased oxidative stress, decreased pro-inflammatory and increased anti-inflammatory cytokine profile with preservation of the Purkinje cell density in the cerebellum, decreased pyknosis in the prefrontal cortex and normalized the expression of GAD67. Thus, HT can be a useful therapeutic agent in ASD and requires further clinical evaluation.

Induction of the Prenylated Stilbenoids Arachidin-1 and Arachidin-3 and Their Semi-Preparative Separation and Purification from Hairy Root Cultures of Peanut (Arachis hypogaea L.).

Prenylated stilbenoids such as arachidin-1 and arachidin-3 are stilbene derivatives that exhibit multiple pharmacological activities. We report an elicitation strategy using different combinations of cyclodextrin, hydrogen peroxide, methyl jasmonate and magnesium chloride to increase arachidin-1 and arachidin-3 production in peanut hairy root cultures. The treatment of hairy root cultures with cyclodextrin with hydrogen peroxide selectively enhanced arachidin-1 yield (132.6 ± 20.4 mg/L), which was 1.8-fold higher than arachidin-3. Similarly, cyclodextrin combined with methyl jasmonate selectively enhanced arachidin-3 yield (178.2 ± 6.8 mg/L), which was 5.5-fold higher than arachidin-1. Re-elicitation of the hairy root cultures further increased the levels of arachidin-1 and arachidin-3 by 24% and 42%, respectively. The ethyl acetate extract of the culture medium was consecutively fractionated by normal- and reversed-phase column chromatography, followed by semi-preparative HPLC purification on a C18 column to yield arachidin-1 with a recovery rate of 32% and arachidin-3 with a recovery rate of 39%, both at higher than 95% purity. This study provided a sustainable strategy to produce high-purity arachidin-1 and arachidin-3 using hairy root cultures of peanuts combined with column chromatography and semi-preparative HPLC.

Marinoquinolones and Marinobactoic Acid: Antimicrobial and Cytotoxic ortho-Dialkylbenzene-Class Metabolites Produced by a Marine Obligate Gammaproteobacterium of the Genus Marinobacterium.

Chemical investigation of the culture extract of a marine obligate proteobacterium, Marinobacterium sp. C17-8, isolated from scleractinian coral Euphyllia sp., led to the discovery of three new o-dialkylbenzene-class metabolites, designated marinoquinolones A (1) and B (2) and marinobactoic acid (3). Spectroscopic analysis using MS and NMR revealed the structures of 1 and 2 to be 4-quinolones with an o-dialkylbenzene-containing side chain at C3 and 3 to be a fatty acid bearing an o-dialkylbenzene substructure. The 4-quinolone form of 1 and 2 was unequivocally determined by comparison of the 1H, 13C, and 15N chemical shifts of 1 with those predicted for 2-methyl-4-quinolone A and its tautomer 2-methyl-4-quinolinol B by quantum chemical calculation. Compound 1 was proven to be racemic by X-ray crystallographic analysis and chiral-phase HPLC analysis of its chemical degradation product. Compounds 1-3 exhibited antimicrobial activity against bacteria and filamentous fungi at MIC of 6.3-50 µg/mL. In addition, all compounds showed cytotoxicity against P388 murine leukemia cells at micromolar ranges.

A preliminary study to evaluate the behavior of Indian population toward E-pharmacy.

The use of the Internet has increased exponentially for buying as well as selling of goods. Even the purchase of medications online is no exception. Owing to its benefits, there are certain risk factors in purchase of online medicines. Currently, the data on the use of Internet pharmacies are limited. Thus, the main objective of our study is to assess the knowledge, attitude, and practices (KAP) of Indian population toward E-pharmacy in India carried out in the Department of Pharmacology, PGIMER, Chandigarh. A KAP questionnaire was prepared which was distributed to the participants through Google Forms and a URL sent to them. This questionnaire was divided into four sections including demographics, occupation, income, and use of the Internet to measure the alertness toward the online purchase of medicines. A total of 322 responses were collected, out of which only 268 (83.2%) participants were aware of online pharmacy. The awareness was more in males and that too in urban population. Among the respondents, majority of the users prefer to buy medicines offline (81%, n = 217) which can be due to poor quality of medicines and lack of trustworthy websites. The utmost reason for buying the medicine online was deficiency of availability in the market and differences in the prices. The most preferred drugs respondents were willing to buy online were prescription drugs followed by cosmetics and dietary supplements. In conclusion, of our results, most of the people use the Internet to search for the medications online who prefer to consult the physicians before buying. Therefore, the future of online pharmacy can be improved if there will be some set guidelines, awareness, and knowledge among the users.

Epigenetic Interface of Autism Spectrum Disorders (ASDs): Implications of Chromosome 15q11-q13 Segment.

Autism spectrum disorders (ASDs) are multifactorial in nature and include both genetic and environmental factors. The increasing evidence advocates an important role of epigenetics in ASD etiology. One of the most common forms of epigenetic changes observed in the case of neurodevelopmental disorders is imprinting which is tightly regulated by developmental and tissue-specific mechanisms. Interestingly, many of these disorders that demonstrate autism-like phenotypes at varying degrees have found involvement of chromosome 15q11-q13 segment. Numerous studies demonstrate occurrence of ASD in the presence of chromosomal abnormalities located mainly in Chr15q11-q13 region. Several plausible candidate genes associated with ASD are in this chromosomal segment, including gamma aminobutyric acid A (GABAA) receptor genes GABRB3, GABRA5 and GABRG3, UBE3A, ATP 10A, MKRN3, ZNF, MAGEL2, Necdin (NDN), and SNRPN. The main objective of this review is to highlight the contribution of epigenetic modulations in chromosome 15q11-q13 segment toward the genetic etiology and pathophysiology of ASD. The present review reports the abnormalities in epigenetic regulation on genes and genomic regions located on chromosome 15 in relation to either syndromic (15q11-q13 maternal duplication) or nonsyndromic forms of ASD. Furthermore, studies reviewed in this article demonstrate conditions in which epigenetic dysregulation has been found to be a pathological factor for ASD development, thereby supporting a role for epigenetics in the multifactorial etiologies of ASD. Also, on the basis of the evidence found so far, we strongly emphasize the need to develop future therapeutic strategies as well as screening procedures for ASD that target mechanisms involving genes located on the chromosomal 15q11-q13 segment.

Neuroprotective effect of 3,3'-diindolylmethane and ɑ-naphthoflavone, aryl hydrocarbon receptor modulators in an experimental model of ischemic stroke.

BACKGROUND: The aryl hydrocarbon receptor (AhR) mediated signaling pathway is being emerged as a current target for neuromodulation. The present study was conducted to characterize the neuroprotective action of AhR modulators, i.e., 3,3'-diindolylmethane (DIM) and ɑ-naphthoflavone (ANF) in an experimental model of stroke using transient middle cerebral artery occlusion (MCAO) in Wistar rats. METHODS: The animals were treated with respective AhR modulators via intraperitoneal (i.p) injection 3 hrs after MCAO for 4 days (at 24 h interval). Following transient MCAO, the brain infarct volume, ND scoring, and various neuro behavioural tests were conducted to confirm the ischemic stroke. Further, oxidative stress parameters, inflammatory cytokines, and apoptotic mRNA expression were assessed. The histopathological changes in the brain of the rats were assessed using H&E staining and the results obtained were correlated with the molecular parameters. RESULTS: Treatment with AhR modulators had significantly decreased the brain infarct volume, ND scoring and improved neuro-behivoral deficits in animals following MCAO. A significant decrease was also observed in the oxidative stress, pro-inflammatory cytokines, and apoptotic mRNA expression in the AhR ligand treated groups. Moreover, a significant improvement was observed in the neuronal damage following MCAO in the treatment groups. CONCLUSION: AhR pathway modulation may be taken as a valuable therapeutic target for treating acute ischemic stroke (AIS).

Tenacibactins K-M, cytotoxic siderophores from a coral-associated gliding bacterium of the genus Tenacibaculum.

HPLC/DAD-based chemical investigation of a coral-associated gliding bacterium of the genus Tenacibaculum yielded three desferrioxamine-class siderophores, designated tenacibactins K (1), L (2), and M (3). Their chemical structures, comprising repeated cadaverine-succinic acid motifs terminated by a hydroxamic acid functionality, were elucidated by NMR and negative MS/MS experiments. Compounds 1-3 were inactive against bacteria and a yeast but displayed cytotoxicity against 3Y1 rat embryonic fibroblasts and P388 murine leukemia cells at GI50 in submicromolar to micromolar ranges. Their iron-chelating activity was comparable to deferoxamine mesylate.

Valproic Acid and Propionic Acid Modulated Mechanical Pathways Associated with Autism Spectrum Disorder at Prenatal and Neonatal Exposure.

Autism spectrum disorder (ASD) is a composite disorder of brain development with uncertain etiology and pathophysiology. Genetic factors are important in ASD causation, although environmental factors are also involved in ASD pathophysiology. Environmental factors might affect the genetic processes of brain development through the modulation of molecular pathways that might be involved with ASD. Valproic acid and propionic acid are the major environmental factors that serve as medicine and food preservative. VPA is used as an anti-epileptic medicine, but it has adverse effects on pregnant women and alters the developmental patterns of the embryo. It is a multi- targeting agent and affects 5-HT, GABA, etc. PPA is a secondary metabolite of gut microbiota that is commonly used as a food preservative. PPA plays a significant role in ASD causation by altering the several developmental molecular pathways like PTEN/Akt, mTOR/Gskß, Cytokines activated pathways, etc., at the prenatal and neonatal stage. Moreover, ASD complexity might be increased by other important factors like vitamin A deficiency. Vitamin A is important for cortical brain development and neuronal cell differentiation. Additionally, several important genes such as RELN, Lhx2, CREB, IL-6, NMDA, BDNF, etc., are also altered in ASD and involved in brain development, central nervous system, and enteric nervous system. These genes affect neuronal differentiation, hyperactivity, oxidative stress, oxytocin, and GABA imbalance lead to improper behavior in autistic individuals. These genes are also studied in VPA and PPA ASD-like animal models. In this review, we explored the mechanical pathways that might be altered with VPA and PPA exposures at the embryonic developmental stage or neonatal developmental stage.

Elicitation of Stilbenes and Benzofuran Derivatives in Hairy Root Cultures of White Mulberry (Morus alba).

Stilbene and benzofuran derivatives isolated from the root of white mulberry (Morus alba) have shown various biological activities, including anti-inflammatory, antioxidant, and antimicrobial properties. The objectives of this study were to develop hairy root cultures and assess the effect of multiple elicitors combinations including (I) methyl-ß-cyclodextrin (CD), MgCl2, methyl jasmonate (MeJA), and H2O2, (II) CD, MgCl2, and MeJA and (III) CD, MgCl2, and H2O2, on the production of these bioactive compounds. The highest yields of stilbenes and benzofurans were obtained upon co-treatment with 18 g/L CD, 3 mM H2O2 and 1 mM MgCl2. The stilbenes oxyresveratrol, resveratrol, and 3'-prenylresveratrol accumulated up to 6.27, 0.61, and 5.00 mg/g DW root, respectively. Meanwhile, the aryl benzofurans moracin M and moracin C accumulated up to 7.82 and 1.82 mg/g DW root, respectively. These stilbenes and benzofurans accumulated in the culture medium of the elicited hairy root cultures. They were not detected in the root tissue. However, the oxyresveratrol diglucoside mulberroside A was only detected in the root tissue with yields up to 10.01 mg/g DW. The results demonstrated that co-treatment of white mulberry hairy root cultures with multiple elicitors can significantly enhance production and secretion of stilbenes and benzofurans in this controlled and sustainable axenic culture system.

Virtual screening and molecular dynamics simulation study of approved drugs as a binder to the linoleic acid binding site on spike protein of SARS-CoV-2 and double mutant (E484Q and L452R).

INTRODUCTION: Binding of linoleic acid (LA) to the spike trimer stabilizes it in closed conformation hindering its binding to angiotensin-converting enzyme-2, thus decreasing infectivity. In the current study, we tend to repurpose Food and Drug Administration-approved drugs as binder to the LA binding pocket in wild and double mutant spike protein. MATERIALS AND METHODS: Approved drugs from DrugBank database (n = 2456) were prepared using Ligprep module of Schrodinger. Crystal structure of LA bound to spike trimer was retrieved (PDB: 6ZB4) and prepared using protein preparation wizard and grid was generated. A virtual screening was performed. With the help of molecular dynamics (MD) studies interaction profile of screened drugs were further evaluated. The selected hits were further evaluated for binding to the double mutant form of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). RESULTS AND DISCUSSION: Following virtual screening, a total of 26 molecules were shortlisted, which were further evaluated using 1ns MD simulation study. Four ligands showing better root mean square deviation (RMSD), RMSD to LA with interaction profile similar to LA were further evaluated using 100 ns MD simulation studies. A total of 2 hits were identified, which performed better than LA (selexipag and pralatrexate). Both these ligands were also found to bind to LA binding site of the double mutant form (E484Q and L452R); however, the binding affinity of pralatrexate was found to be better. CONCLUSION: We have identified 2 ligands (selexipag and pralatrexate) as possible stable binders to the LA binding site in spike trimer (wild and mutant form). Among them, pralatrexate has shown in vitro activity against SARS-CoV-2, validating our study results.

Neuroprotective effect of bone marrow-derived mesenchymal stem cell secretome in 6-OHDA-induced Parkinson's disease.

Aim: The aim of the study was to evaluate the neuroprotective effect of bone marrow stem cell secretome in the 6-hydroxydopamine (6-OHDA) model of Parkinson's disease. Materials & methods: Secretome prepared from mesenchymal stem cells of 3-month-old rats was injected daily for 7 days between days 7 and 14 after 6-OHDA administration. After 14 days, various neurobehavioral parameters were conducted. These behavioral parameters were further correlated with biochemical and molecular findings. Results & conclusion: Impaired neurobehavioral parameters and increased inflammatory, oxidative stress and apoptotic markers in the 6-OHDA group were significantly modulated by secretome-treated rats. In conclusion, mesenchymal stem cell-derived secretome could be further explored for the management of Parkinson's disease.

Update on geographical variation and distribution of SARS-nCoV-2: A systematic review.

Knowledge of a new mutant strain of SARS-coronavirus (CoV-2) is enormously essential to identify a targeted drug and for the development of the vaccine. In this article, we systematically reviewed the different mutation strains (variant of concern [VOC] and variant of interest [VOI]) which were found in different countries such as the UK, Singapore, China, Germany, Vietnam, Western Africa, Dublin, Ireland, Brazil, Iran, Italy, France, America, and Philippines. We searched four literature databases (PubMed, EMBASE, NATURE, and Willey online library) with suitable keywords and the time filter was November 2019 to June 16, 2021. To understand the worldwide spread of variants of SARS-CoV-2, we included a total of 27 articles of case reports, clinical and observational studies in the systematic review. However, these variants mostly spread because of their ability to increase transmission, virulence, and escape immunity. So, in this paper is we found mutated strains of SARS-CoV-2 like VOCs that are found in different regions across the globe are ALPHA strain in the U.K, BETA strain in South Africa, GAMMA strain in Brazil, Gamma and Beta strains in European Countries, and some VOIs like Theta variant in the Philippines.

Promising traditional Indian medicinal plants for the management of novel Coronavirus disease: A systematic review.

Traditional Indian medical practices (Ayurveda, Siddha, Unani, and homeopathy) are a vast reservoir of knowledge about medicinal plants. The promising pharmacological properties of these plants have paved the way for developing therapy against novel Coronavirus (CoV) infection. The current review will summarize published works of literature on the effects of traditional Indian medicinal plants against acute respiratory infection (COVID-19, SARS, Influenza, and Respiratory syncytial virus infection) and registered clinical trials of traditional Indian herbal medicines in COVID-19. The current study aims to comprehensively evaluate the data of traditional Indian medicinal plants to warrant their use in COVID-19 management. PubMed, Embase, and Cochrane databases were searched along with different clinical trial databases. A total of 22 relevant traditional Indian medicinal plants (35 relevant studies) were included in the current study having potential antiviral properties against virus-induced respiratory illness along with promising immunomodulatory and thrombolytic properties. Further, 36 randomized and nonrandomized registered clinical trials were also included that were aimed at evaluating the efficacy of herbal plants or their formulations in COVID-19 management. The antiviral, immunomodulatory, and thrombolytic activities of the traditional Indian medicinal plants laid down a strong rationale for their use in developing therapies against SARS-CoV-2 infection. The study identified some important potential traditional Indian medicinal herbs such as Ocimum tenuiflorum, Tinospora cordifolia, Achyranthes bidentata, Cinnamomum cassia, Cydonia oblonga, Embelin ribes, Justicia adhatoda, Momordica charantia, Withania somnifera, Zingiber officinale, Camphor, and Kabusura kudineer, which could be used in therapeutic strategies against SARS-CoV-2 infection.