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In eastern India, the tubers of Pueraria tuberosa (Willd.) DC. are used by the ethnic communities for its wide range of medicinal and nutritional value, especially to rejuvenate livestock health and to treat helminthiasis. The study is aimed to evaluate the ethnoveterinary medicinal importance of P. tuberosa as anthelmintic, to verify its nontoxic nature and identify the most potent phytoconstituents aided by in silico molecular docking technique. Ethnomedicinal data collected from 185 informants were quantitatively analyzed employing eight quantitative indices to highlight the use diversity and most frequently used part of the plant. High scores of certain indices employed, such as Use Value (UV = 0.52), Fidelity Level (FL = 68.42%) and Tissue Importance Value (TIV = 1) clearly illustrate an ethnomedicinal lead regarding medico-nutritional benefits of the tuber part used against intestinal helminthic diseases of veterinary animals. Based on this ethno-guided lead, root tuber has been investigated for its chemical profiling by the estimation of total phenolics, flavonoids, tannins and alkaloids, along with HPLC and GC-MS analyses. Anthelmintic property was evaluated with the tuber extracts by in vitro studies on some helminths of livestock and poultry birds, and it showed promising results against the tested parasites namely Cotylophoron cotylophorum, Raillietina tetragona and Setaria cervi. Toxicity assessments of tuber extract through in vitro and in vivo methods were performed using Vero cells and BALB/c mice. Nontoxic nature of the studied tuber extract was observed even in higher experimental doses. Out of 12 phytocompounds identified by GC-MS analysis, one compound [Morphinan-4,5-epoxy-3,6-di-ol,6- (7-nitrobenzofurazan-4-yl) amino-] exhibited the best binding conformations in cost of the lowest binding energy values with six target proteins that include one anti-inflammatory, one antioxidant, and four anthelmintic proteins. The findings of our study are found very encouraging to evaluate this tuber drug furthermore intensively towards the development of anthelmintic veterinary medicine. [ABSTRACT FROM AUTHOR]

Periodontal diseases are highly prevalent oral conditions associated with severe complications in the oral cavity. These inflammatory diseases are caused by the oral microbiome and are influenced by several factors, such as aging, tobacco usage, systemic illness and inadequate oral hygiene. Plant-derived phytochemicals are extensively utilized in managing various periodontal diseases due to the presence of antioxidant, anti-inflammatory and antibacterial activities. Plant materials have shifted attention from conventional medicine to indigenous medicine. Solanum xanthocarpum is a medicinal herb found in India. It exhibits various pharmacological properties essential for periodontal disease prevention and management. The current work analyzes various pharmacological properties of S. xanthocarpum aqueous extract. The S. xanthocarpum extracts' antioxidant, anti-inflammatory and anti-microbial properties were ascertained by DPPH assay, HRBC membrane stabilization assay and disk diffusion assay, respectively. S. xanthocarpum's active phytochemical components were detected using gas chromatography–mass spectrometry (GC-MS) estimation. Furthermore, molecular docking and simulation analysis were conducted to determine the interaction between phytocompounds and the RgpB protein of Porphyromonas gingivalis. Phytocompounds possessing anti-microbial, antioxidant and anti-inflammatory properties were detected through GC-MS estimation. The molecular docking and simulation analysis revealed the inhibitory mechanisms of the phytocompounds Solasodine, Lupeol and Quercetin against arginine-specific gingipain RgpB protein. Insilico analysis revealed that Lupeol had the highest binding energy of −263.879 Kcal/mol among the phytocompounds studied, followed by Solasodine with a binding energy of −102.457 Kcal/mol and Quercetin with a binding energy of 33.6821 Kcal/mol. The study revealed that S. xanthocarpum has significant potential as an herbal remedy for preventing and treating periodontal diseases. This may facilitate drug development in the future. [ABSTRACT FROM AUTHOR]

Mucormycosis is an insidious fungal infection caused by members of Mucorales and zygomycotic species. During the last few years, mucormycosis has become the third most common invasive fungal infection in patients with haematological malignancies and organ transplantations. The incidence of mucormycosis is particularly high in patients with immunocompromised health. It has been reported that CotH receptor proteins have a potential role in binding Rhizopus species with the host cells. Further, CotH1, CotH2, and CotH3 are the spore-coating protein of mucormycosis, which are mostly responsible for the invasion of host cells and causing diseases. The present study aimed to predict the structure of CotH1, CotH2, and CotH3 receptors in Rhizpous delemar using homology modelling on SWISS Server and validated the model based on GMQE and QMEAN scores followed by analysis of the predicted model on Ramachandran plot. Further, molecular docking studies of the predominant 46 phytochemicals found in the medicinal plants of Uttarakhand region, India were done against these three receptors. Autodock vina results have shown that the binding energy value of Curcumin was -8.5 Kcal/mol against CotH1, and the binding energy value of Allosecurinin was -7.6 Kcal/mol against CotH2 and binding energy value of Isoquercetin was -7.7 Kcal/mol against CotH3. Evaluation of the ADMET parameters has shown the high efficacy of these compounds. The present Insilico study suggests that Curcumin, Allosecurinine, and Isoquercetin are effective lead molecules against the receptors CotH1, CotH2, and CotH3 in the mucormycosis caused by fungal species R. delemar. [ABSTRACT FROM AUTHOR]

The seed of Cycas pectinata is widely used in traditional practices in the Northeastern region of India for diverse purposes along with improving testicular functions. Thus, it may be hypothesized that the phytochemicals of C. pectinata seed could modulate testicular steroidogenesis. Therefore, we have investigated the effects of C. Pectinata seed extract (CPE) on testicular steroidogenesis by using in vivo and in vitro approaches. We have also performed the molecular docking of phytochemicals with some steroidogenic markers based on the identified phytochemicals from our previous study. The in vivo treatment of CPE increased the circulating estrogen and decreased circulating testosterone. The in vitro treatment of CPE also showed increased secretion of estrogen which can be suggested due to an increase in the aromatase (CYP19A1) activity. Our results also showed that the expression and localization of CYP19A1 were elevated by the CPE. The treatment of CPE also showed an accumulation of cholesterol in the testis, which could enhance testicular steroidogenesis. The other steroidogenic markers like 3βHSD, StAR, and LHR were upregulated by the CPE. Twelve compounds exhibited binding energy in the range of -10.0 to -8.0 kcal/mol with CYP19A1. Our data from in vitro, in vivo, and docking studies, showed that phytochemicals of CPE could modulate testicular steroidogenesis. [ABSTRACT FROM AUTHOR]

The wild-type SARS-CoV-2 has continuously evolved into several variants with increased transmissibility and virulence. The Delta variant which was initially identified in India created a devastating impact throughout the country during the second wave. While the efficacy of the existing vaccines against the latest SARS-CoV-2 variants remains unclear, extensive research is being carried out to develop potential antiviral drugs through approaches like in silico screening and drug-repurposing. This study aimed to conduct the docking-based virtual screening of 50 potential phytochemical compounds against a Spike glycoprotein of the wild-type and the Delta SARS-CoV-2 variant. Subsequently, molecular docking was performed for the five best compounds, such as Lupeol, Betulin, Hypericin, Corilagin, and Geraniin, along with synthetic controls. From the results obtained, it was evident that Lupeol exhibited a remarkable binding affinity towards the wild-type Spike protein (−8.54 kcal/mol), while Betulin showed significant binding interactions with the mutated Spike protein (−8.83 kcal/mol), respectively. The binding energy values of the selected plant compounds were slightly higher than that of the controls. Key hydrogen bonding and hydrophobic interactions of the resulting complexes were visualized, which explained their greater binding affinity against the target proteins—the Delta S protein of SARS-CoV-2, in particular. The lower RMSD, the RMSF values of the complexes and the ligands, Rg, H-bonds, and the binding free energies of the complexes together revealed the stability of the complexes and significant binding affinities of the ligands towards the target proteins. Our study suggests that Lupeol and Betulin could be considered as potential ligands for SARS-CoV-2 spike antagonists. Further experimental validations might provide new insights for the possible antiviral therapeutic interventions of the identified lead compounds and their analogs against COVID-19 infection. [ABSTRACT FROM AUTHOR]

Since the start of the pandemic, SARS-CoV-2 has already infected more than 250 million people globally, with more than five million fatal cases and huge socio-economic losses. In addition to corticosteroids, and antiviral drugs like remdesivir, various immunotherapies including monoclonal antibodies (mAbs) to S protein of SARS-CoV-2 have been investigated to treat COVID-19 patients. These mAbs were initially developed against the wild-type SARS-CoV-2; however, emergence of variant forms of SARS-CoV-2 having mutations in the spike protein in several countries including India raised serious questions on the potential use of these mAbs against SARS-CoV-2 variants. In this study, using an in silico approach, we have examined the binding abilities of eight mAbs against several SARS-CoV-2 variants of Alpha (B.1.1.7) and Delta (B.1.617.2) lineages. The structure of the Fab region of each mAb was designed in silico and subjected to molecular docking against each mutant protein. mAbs were subjected to two levels of selection based on their binding energy, stability, and conformational flexibility. Our data reveal that tixagevimab, regdanvimab, and cilgavimab can efficiently neutralize most of the SARS-CoV-2 Alpha strains while tixagevimab, bamlanivimab, and sotrovimab can form a stable complex with the Delta variants. Based on these data, we have designed, by in silico , a chimeric antibody by conjugating the CDRH3 of regdanivimab with a sotrovimab framework to combat the variants that could potentially escape from the mAb-mediated neutralization. Our finding suggests that though currently available mAbs could be used to treat COVID-19 caused by the variants of SARS-CoV-2, better results could be expected with the chimeric antibodies. [ABSTRACT FROM AUTHOR]

In this investigation, potential inhibitors of α-amylase, one of the key regulatory enzymes in diabetes were characterized from the methanolic extract of Leucas ciliata Benth. (Lamiaceae), a traditional medicinal plant of the Western Ghats, southern India and the ethyl acetate extract of Streptomyces longisporoflavus (JX965948), an endophytic actinomycete isolated from the stem fragments of L. ciliata, by Gas Chromatography and Mass Spectroscopy (GC–MS) technique followed by molecular docking studies. Forty-four compounds were detected in the solvent extracts of the host plant and the endophyte, respectively. These compounds were selected as ligands for the receptor α-amylase in the molecular docking studies using PyRx software (0.8 V) for the inhibition of α-amylase activity. The ligands were ranked based on the binding energies ranging between − 3.1 and − 10.1 kcal/mol. Three ligands from the host plant extract, viz., Topotecan (PNo_7), Cathine (PNo_17) and 2,5-dimethoxy-4-(methylsulfonyl)amphetamine (PNo_18), depicted good binding energies of − 5.2 to − 7.8, respectively, whereas seven compounds from the endophyte extract showed binding energies in the range of − 4.7 to − 10.1, respectively. The standard α-amylase inhibitor Acarbose™ depicted binding energy of − 9.2 kcal/mol. All ligands were subjected to lead-likeliness property using Lipinski's rule of five. On the basis of the hydrogen bonding interactions with the receptor, and chemoinformatics analysis for drug-likeliness, one ligand, Topotecan (PNo_7) from the host plant was identified as the potential α-amylase inhibitor. This is the first attempt to identify alkaloid and flavonoid compounds as the α-amylase inhibitors from the host plant and its endophyte simultaneously. The molecular docking analyses presented in this study could lead to the development of potent α-amylase inhibitors helpful in the treatment of diabetes. [ABSTRACT FROM AUTHOR]

Infection from Campylobacter jejuni causes intense enteritis with diarrhea, fever and abdominal pain. The peptide-based vaccine could be the best way to deal with the immune response especially when antibiotic resistance is increasing in bacteria. In this study, Vaxign Server was used to predict the vaccine targets by computing proteome of diarrheagenic Campylobacter jejuni strain NCTC 11168 using default parameters. NetMHC II 2.3 server and Vaxijen tool were used to screen epitopes from protein and to identify the most antigenic epitopes binding with MHC class II molecules, respectively. Three potent T cell epitopes YFYGLAGGG, PFIMFSMLM and YIILNNFKI were screened binding with HLA-DRB1*10:01, HLA-DRB1*01:03, HLA-DRB1*04:01 and HLA-DRB1*07:01 MHC class II alleles, respectively. PepstrMod and Swiss-Model server were used to build a 3D structure model of epitopes and alleles, respectively. Identified epitopes were further docked with HLA alleles using AutoDock Vina tool to confirm binding ability. The epitopes YFYGLAGGG and PFIMFSMLM had a binding affinity of − 6.3 kcal/mol and − 6.1 kcal/mol with HLA-DRB1*10:01 and HLA-DRB1*01:03 alleles, respectively. Epitope YIILNNFKI had binding energy − 6.1 kcal/mol with two alleles HLA-DRB1*04:01 and HLA-DRB1*07:01. The predicted epitope-allele docked complex structure was optimized using molecular dynamics simulation and stability of complex structure was evaluated. These predicted epitopes were found to cover a maximum number of populations coverage in India as well as worldwide. Therefore, these epitopes had the most potential to induce T cell-mediated immune response and potent vaccine candidates against Campylobacter jejuni after testing by experimental study. [ABSTRACT FROM AUTHOR]

Introduction: Malaria, a tropical disease, caused by Plasmodium is curable; still, the burden of malaria infection exists in third world countries. India, particularly among the South-East Asian region, has the maximum mortality rate. The parasites have developed resistance against antimalarial drugs. Alternatively, plants are the most important and ancient source of the drug and spices, in particular, are being used to treat various ailments. Aim: To identify the effect of common Indian spices in targeting malarial proteases. Materials and Methods: A bioinformatics approach was used to target malarial proteases which exhibit an important role in the erythrocytic cycle of the pathogen by degrading Haemoglobin. Proteases, in particular, Falcipain and Plasmepsin were used to perform docking studies to identify potent molecule for inhibition of malarial progression. Data were collected in the form of structural files from PDB (for protein) and PubChem (for ligands). The Protein structures and ligands were prepared and molecular docking had been done to predict interactions. Results: All the eighteen compounds used in study have shown quite a good affinity with target proteins in the terms of energy (negative binding energy). However, comparatively, interactions of falcipain 2 with thymol and gingerol were almost three times lower than other ligand. Except these, energy ranges were in between 30-40 kilo Joule in negative. Strongest interactions were found in between Plasmepsin 4-piperamide and plasmepsin 2-gingerol. Also, it was found that gingerol was most potent bioactive molecule interacting with almost all proteins as predicted by docking studies. Conclusion: Plasmepsin 2 and Plasmepsin 4 with gingerol and piperamide with highest cdocker energy might indicate the potential of molecules in targeting these proteases. Also, Gingerol was found to be most potent in interacting with malarial proteases. [ABSTRACT FROM AUTHOR]

The generation of antimicrobial-resistant bacteria largely depends on the use of antimicrobials not only in humans but also in pet animals and livestock. The present study was conducted to detect the occurrence of beta-lactamase and biofilm-producing- E.coli in healthy pet and backyard livestock. The study also intended on molecular docking experiments to confirm the nature of the catalytic mechanism in β-lactamase enzymes, encoded by the various bla CTX-M genotypes and phylogenetic analysis to reveal clonal relationship of the animal origin E. coli isolates with human clinical strains. The rectal swabs were collected from healthy dogs (n = 254), cats (n = 108), sheep (n = 119) and goats (n = 143) in India. In total 247 (76.47%) E. coli strains were identified as ESBL producers. The possession of ESBL-producers was significantly more (p < 0.05) in pets than in the backyard livestock. Most of the strains possessed bla CTX-M-15 like clones. E. coli strains possessing bla CTX-M-15.2 , bla CTX-M-157 , bla CTX-M-181 and bla CTX-M-218 like clones, isolated from pets were not reported earlier. The study detected 56.65% of E. coli strains as moderate or strong biofilm producers possessing biofilm-associated genes (csgA , rcsA , rpoS, sdiA). ESBL-producing E. coli showed phenotypical resistance to tetracycline (93.1%), azithromycin (89.8%), ampicillin (84.2%), cefotaxime (80.9%), doxycycline (82.5%), co-trimoxazole (80.9%), ampicillin/cloxacillin (76.9%). The CTX-M variants obtained in this study were modelled by the SWISS-MODEL and verified. Ligand having minimum binding energy, show the highest affinity of β-lactamases for cefotaxime and cefpodoxime. The Gibbs free energy release for all 14 different complex ranges between −6.9 (CTX-M-15.2+cefpodoxime) to −5.3 (CTX-M-218+cefpodoxime) Kcal/mol. Phylogenetic analysis of the animal origin ESBL- E. coli strains revealed a partial clonal relationship with the clinical isolates of local human patients. The present study described the significant presence of biofilm and β-lactamase producing, multi-drug resistant E. coli in pet animals having public health importance. [Display omitted] • First large-scale monitoring of ESBL/biofilm producing- E. coli in companion/backyard animals in India. • Majority of the strains isolated from both companion/household animals possessed bla CTX-M-15. • Canine E. coli possessing bla CTX-M-15.2 , bla CTX-M-157 , bla CTX-M-181, bla CTX-M-181 and bla CTX-M-218 are not reported earlier. • Docking of CTX-M variants revealed the ligands showing highest affinity of β-lactamases for cefotaxime and cefpodoxime. • The animal isolates were clonally related to the local human clinical strains. [ABSTRACT FROM AUTHOR]

• Monochoria hastata (L.) Solms extracts, used by native poor villagers as antiviral drug in various parts of India, showed potential binding with Mpro of SARS-CoV-2. • Virtual screening of 20 compounds extracted from Monochoria hastata (L.) Solms showed azelaic dihydrazide (ADZ) has the highest binding affinity. • RMSD and RMSF plots, sequence analysis and binding energy analysis supports the potentiality of the drug ADZ against Mpro. • Evaluation of thermodynamic parameters revealed that there is a robust conformational change of Mpro by the drug. Using molecular docking and other studies, 20 compounds extracted from Monochoria hastata (L.) Solms were screened, and their inhibitory efficiency examined against main protease (3CLpro) of SARS CoV-2. All the compounds were found to binding with 3CLpro through van der Waals and electrostatic forces of attractions. Among them, Azelaic dihydrazide (ADZ) was found to have the highest docking score. 3CLpro-ADZ complex was studied by MD simulation. ADZ was found to disrupt the structure of 3CLpro after 2 ns. RMSD and RMSF analysis along with sequence and binding energy analysis suggest that ADZ can be a potential drug against SARS CoV-2. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: New Delhi metallo-β-lactmase-1 (NDM-1) is an enzyme that confers antibiotic resistance to bacteria and is thus a serious threat to human health. Almost all clinically available β-lactam antibiotics can be hydrolyzed by NDM-1. To determine the mechanism behind the wide substrate diversity and strong catalytic ability of NDM-1, we explored the molecular interactions between NDM-1 and different β-lactam antibiotics using computational methods. Molecular dynamics simulations and binding free energy calculations were performed on enzyme-substrate (ES) complex models of NDM-1-Meropenem, NDM-1-Nitrocefin, and NDM-1-Ampicillin constructed by molecular docking. Our computational results suggest that mutant residues Ile35 and Lys216, and active site loop L1 residues 65–73 in NDM-1 play crucial roles in substrate recognition and binding. The results of our study provide new insights into the mechanism behind the enhanced substrate binding and wider substrate spectrum of NDM-1 compared with its homologous enzymes CcrA and IMP-1. These insights may be useful in the discovery and design of specific and potent inhibitors against NDM-1. [Copyright &y& Elsevier]

The question of how to reconcile China and India's growing greenhouse gas emissions with their right to economic development has been a major impediment to a comprehensive global climate change mitigation agreement. Developed nations such as the US and Australia have demanded China and India accept binding emissions targets, which the two Asian powerhouses have refused to do to date, This article compares and contrasts the climate change mitigation policies of the Chinese and Indian governments and evaluates whether these policies could potentially create an alternative pathway towards reducing greenhouse gas emissions without the need for binding emissions targets in the immediate future, The article proposes that binding energy efficiency and renewable energy targets may act as a shadow target - a substitute for a binding emissions target. It concludes that China and India's programmes have the potential to become templates for this model, provided they are backed by adequate monitoring infrastructure and investment. As such, they could potentially provide a compromise option between the divergent positions of developed and developing nations on carbon mitigation targets during the post-Kyoto negotiations. [ABSTRACT FROM AUTHOR]

A drug repurposing strategy could be a potential approach to overcoming the economic costs for diabetes mellitus (DM) treatment incurred by most countries. DM has emerged as a global epidemic, and an increase in the outbreak has led developing countries like Mexico, India, and China to recommend a prevention method as an alternative proposed by their respective healthcare sectors. Incretin-based therapy has been successful in treating diabetes mellitus, and inhibitors like sitagliptin, vildagliptin, saxagliptin, and alogliptin belong to this category. As of now, drug repurposing strategies have not been used to identify existing therapeutics that can become dipeptidyl peptidase-4 (DPP-4) inhibitors. Hence, this work presents the use of bioinformatics tools like the Activity Atlas model, flexible molecular docking simulations, and three-dimensional reference interaction site model (3D-RISM) calculations to assist in repurposing Food and Drug Administration (FDA)-approved drugs into specific nonsteroidal anti-inflammatory medications such as DPP-4 inhibitors. Initially, the Activity Atlas model was constructed based on the top scoring DPP-4 inhibitors, and then the model was used to understand features of nonsteroidal anti-inflammatory drugs (NSAIDs) as a function of electrostatic, hydrophobic, and active shape features of DPP-4 inhibition. The FlexX algorithm was used to infer protein–ligand interacting residues, and binding energy, to predict potential draggability towards the DPP-4 mechanism of action. 3D-RISM calculations on piroxicam-bound DPP-4 were used to understand the stability of water molecules at the active site. Finally, piroxicam was chosen as the repurposing drug to become a new DPP-4 inhibitor and validated experimentally using fluorescence spectroscopy assay. These findings are novel and provide new insights into the role of piroxicam as a new lead to inhibit DPP-4 and, taking into consideration the biological half-life of piroxicam, it can be proposed as a possible therapeutic strategy for treating diabetes mellitus. [ABSTRACT FROM AUTHOR]