Prediction of In-silico ADMET Properties and Molecular docking study of Substituted Thiadiazole for screening of Antiviral activity against protein target Covid-19 main protease

Abstract

The SARS-CoV-2 virus is the infectious disease known as coronavirus disease (COVID-19). The majority of COVID-19 patients will have mild to moderate symptoms and recover without additional care. However, some people will get serious illnesses and need medical attention. Designing novel medications and testing them for inhibitory action against the corona virus's primary targets could be a successful technique for the advancement of the drug discovery process and the treatment of corona virus disease in the context of the COVID-19 pandemic, which is spreading quickly. The objective of this work was to evaluate the physical-chemical, pharmacokinetic parameters (absorption, distribution, metabolism, excretion and toxicity) and pharmacodynamic parameters (bioactivity and adverse reactions) of Substituted thiadiazole by means of in-silico computational prediction. Online software such as Pre-ADMET, Molinspiration and Rule of Five were used for the analysis. In-silico results allow us to conclude that substituted thiadiazole is predicted to be a potential future drug candidate, due to its relevant Drug-likeness profile, bioavailability, excellent liposolubility and adequate pharmacokinetics, including at the level of CNS, penetrating the blood-brain barrier. Molecular docking studies of 20 designed compounds have also been performed to screen the inhibitory activity towards against protein target COVID-19 main protease (PDB: 6LU7). Among all the compounds C3 exhibited the most significant affinity score against COVID-19 main protease (PDB: 6LU7) and Shown best significant hydrogen bonds interaction at the active site of protein.