Coronavirus disease-2019 (COVID-19) is a global health emergency and the matter of serious concern, which has been declared a pandemic by WHO. Till date, no potential medicine/ drug is available to cure the infected persons from SARS-CoV-2. This deadly virus is named as novel 2019-nCoV coronavirus and caused coronavirus disease, that is, COVID-19. The first case of SARS-CoV-2 infection in human was confirmed in the Wuhan city of the China. COVID-19 is an infectious disease and spread from man to man as well as surface to man . In the present work, in silico approach was followed to find potential molecule to control this infection. Authors have screened more than one million molecules available in the ZINC database and taken the best two compounds based on binding energy score. These lead molecules were further studied through docking against the main protease of SARS-CoV-2. Then, molecular dynamics simulations of the main protease with and without screened compounds were performed at room temperature to determine the thermodynamic parameters to understand the inhibition. Further, molecular dynamics simulations at different temperatures were performed to understand the efficiency of the inhibition of the main protease in the presence of the screened compounds. Change in energy for the formation of the complexes between the main protease of novel coronavirus and ZINC20601870 as well ZINC00793735 at room temperature was determined on applying MM-GBSA calculations. Docking and molecular dynamics simulations showed their antiviral potential and may inhibit viral replication experimentally. Communicated by Ramaswamy H. Sarma

Literature reported that nsp3 of CHIKV is an important target for the designing of drug as it involves in the replication, survival etc. Herein, about eighteen million molecules available in the ZINC database are filtered against nsp3 using RASPD. Top five hit drug molecules were then taken from the total screened molecules (6988) from ZINC database. Then, a one pot-three components reaction is designed to get the pyrazolophthalazine and its formation was studied using DFT method. Authors created a library of 200 compounds using the product obtained in the reaction and filtered against nsp3 of CHIKV based on docking using iGEMDOCK, a computational tool. Authors have studied the best molecules after applying the the Lipinski's rule of five and bioactive score. Further, the authors took the best compound i.e. CMPD178 and performed the MD simulations and tdMD simulations with nsp3 protease using AMBER18. MD trajectories were studied to collect the information about the nsp3 of CHIKV with and without screened compound and then, MM-GBSA calculations were performed to calculate change in binding free energies for the formation of complex. The aim of the work is to find the potential candidate as promising inhibitor against nsp3 of CHIKV.

The widespread use of pesticides poses significant threats to both environmental and human health, primarily due to their potential toxic effects. The study investigated the cardiovascular toxicity of selected pesticides, focusing on their interactions with Toll-like receptor 4 (TLR4), an important part of the innate immune system. Using computational tools such as molecular docking, molecular dynamics (MD) simulations, principal component analysis (PCA), density functional theory (DFT) calculations, and ADME analysis, this study identified C160 as having the lowest binding affinity (-8.2 kcal/mol), followed by C107 and C165 (-8.0 kcal/mol). RMSD, RMSF, Rg, and hydrogen bond metrics indicated the formation of stable complexes between specific pesticides and TLR4. PCA revealed significant structural changes upon ligand binding, affecting stability and flexibility, while DFT calculations provided information about the stability, reactivity, and polarity of the compounds. ADME studies highlighted the solubility, permeability, and metabolic stability of C107, C160, and C165, suggesting their potential for bioavailability and impact on cardiovascular toxicity. C107 and C165 exhibit higher bioactivity scores, indicating favourable absorption, metabolism, and distribution properties. C165 also violated rule where molecular weight is greater than 500 g/mol. Further, DFT and NCI analysis of post MD conformations confirmed the binding of ligands at the binding pocket. The analysis shed light on the molecular mechanisms of pesticide-induced cardiovascular toxicity, aiding in the development of strategies to mitigate their harmful effects on human health.