Bovine milk is an important food component in the human diet due to its nutrient-rich metabolites. However, bovine subclinical mastitis alters the composition and quality of milk. In present study, California mastitis testing, somatic cell count, pH, and electrical conductivity were used as confirmatory tests to detect subclinical mastitis. The primary goal was to study metabolome and identify major pathogens in cows with subclinical mastitis. In this study, 29 metabolites were detected in milk using gas chromatography–mass spectrometry. Volatile acidic compounds, such as hexanoic acid, hexadecanoic acid, lauric acid, octanoic acid, n-decanoic acid, tricosanoic acid, tetradecanoic acid, and hypogeic acid were found in milk samples, and these impart good flavor to the milk. Metaboanalyst tool was used for metabolic pathway analysis and principal component estimation. In this study, EC and pH values in milk were significantly increased (p < 0.0001), whereas fat (p < 0.04) and protein (p < 0.0002) significantly decreased in animals with subclinical mastitis in comparison to healthy animals. Staphylococcus aureus was the predominant pathogen found (n = 54), followed by Escherichia coli (n = 30). Furthermore, antibiotic sensitivity revealed that Staphylococcus aureus was more sensitive to gentamicin (79.6%), whereas Escherichia coli showed more sensitivity to doxycycline hydrochloride (80%).

P53 is eminent tumour suppressor protein that plays a prominent role in cell cycle arrest, DNA repair, senescence, differentiation and initiation of apoptosis. P53 is an attractive drug target and the high toxicity of some cancer chemotherapy drugs increase the demand for new anti-cancer drugs from natural products. In this current scenario, identification of promising anticancer compounds from natural sources by repurposing approach is still relevant for the early prevention and effective management of cancer. In present study, we docked natural compounds like podophyllotoxin, quercetin and rutin along standard drugs (MG-132 and Bay 61-3606) against p53 protein. ADME/T analysis predicted toxicity of phytochemicals and drugs. In silico docking analysis of podophyllotoxin, quercetin and rutin gave HDOCK docking scores of −187.87, −148. 97 and −143.85, whereas control drugs MG-132 and Bay 61-3606 showed docking scores of −159.59 and −140.71 against p53 respectively. AutoDock analysis of rutin and MG-132 showed highest binding affinity scores of −7.3 and −6.8 kcal/mol against p53. Molecular dynamic simulation for p53 protein displayed stable conformation and convergence. In this study, P53-rutin complex showed free binding energy score of 11.84 kcal/mol and P53-MG-132 complex reported free energy score of 16.3 kcal/mol. Protein contacts atlas gives non-covalent contacts framework by exploring interfaces of individual subunits and protein-ligand interactions. STRING tool predicts physical and functional interactions between proteins. The results of this study revealed that rutin and MG-132 could be promising inhibitors against targeted p53 protein and this could prove detrimental for molecular therapeutics and drug-designing strategies. Communicated by Ramaswamy H. Sarma

COVID-19 has infected millions and significantly affected the global economy and healthcare systems. Despite continuous lockdowns, symptomatic management with currently available medications, and numerous vaccination drives, it is still far more difficult to control. Against COVID-19 infection, the pressure to develop vaccines and drugs has led to using some currently available medications like remdesivir, azithromycin, hydroxychloroquine and ritonavir. Understanding the importance and potential of harmless molecules to tackle SARS-COV-2, we designed the present study to identify potential natural phytocompounds. In the present study, we docked natural compounds and standard drugs against SARS-COV-2 proteins: papain-like protease, main protease and helicase. ADME/T and ProTox-II analyses were used to determine the toxicity of phytocompounds and drugs. The docking analysis revealed that podophyllotoxin gave the highest binding affinity scores of −8.1, −7.1 and −7.4 kcal/mol against PLpro, Mpro and helicase, respectively. Among the control drugs, doxycycline hydrochloride showed the highest binding affinity of −10.5, −8.4 and −8.8 kcal/mol against PLpro, Mpro and helicase. The results of this study revealed that podophyllotoxin and doxycycline hydrochloride could be promising inhibitors against SARS-Cov-2. Molecular dynamic simulations were executed for the best docked (PLpro-podophyllotoxin) complex, and the results displayed stable conformation and convergence. Energy plot results predicted a global minima average energy of −95 kcal/mol and indicated podophyllotoxin’s role in stabilizing protein and making it compact and complex. FarPPI server used MM/GBSA approach to determine free binding affinity, and helicase–gallic acid complex showed the highest affinity, respectively. Therefore, it can be concluded that there is still a need for in vitro and in vivo studies to support further and validate these findings and validate these findings. Communicated by Ramaswamy H. Sarma