Molecular docking approaches and its significance in assessing the antioxidant properties in different compounds.

In the last few years, the significance of antioxidant compounds and their properties has attracted great interest from the scientific community. The role of an antioxidant in managing & regulating oxidative stress and also in the protection of the human body from severe adverse effects due to excess release of free radicles or reactive oxygen species (ROS) is remarkable. From aiding protection & combating severe illnesses such as cancer, neurodegeneration, aging, and diabetes to being a vital part of the treatment of SARs-CoV-19 is of great importance. Therefore, the study of anti-oxidants is of great importance in human sustenance. Additionally, molecular docking techniques and their various mathematical features help in understanding the molecular interactions of anti-oxidants based on their lowest binding energy. The evaluation of the binding score between two constituent molecules will provide insight as to the binding process and also suggest possible novel therapeutic targets for the treatment of diseases. In this chapter, we will discuss the significance of molecular docking techniques in the study of antioxidant compounds.

A molecular dynamics simulation study of the ACE2 receptor with screened natural inhibitors to identify novel drug candidate against COVID-19.

BACKGROUND & OBJECTIVES: The massive outbreak of Novel Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) has turned out to be a serious global health issue worldwide. Currently, no drugs or vaccines are available for the treatment of COVID-19. The current computational study was attempted to identify a novel therapeutic inhibitor against novel SARS-CoV-2 using in silico drug discovery pipeline. METHODS: In the present study, the human angiotensin-converting enzyme 2 (ACE2) receptor was the target for the designing of drugs against the deadly virus. The 3D structure of the receptor was modeled & validated using a Swiss-model, Procheck & Errat server. A molecular docking study was performed between a group of natural & synthetic compounds having proven anti-viral activity with ACE2 receptor using Autodock tool 1.5.6. The molecular dynamics simulation study was performed using Desmond v 12 to evaluate the stability and interaction of the ACE2 receptor with a ligand. RESULTS: Based on the lowest binding energy, confirmation, and H-bond interaction, cinnamic acid (-5.20 kcal/mol), thymoquinone (-4.71 kcal/mol), and andrographolide (Kalmegh) (-4.00 kcal/mol) were screened out showing strong binding affinity to the active site of ACE2 receptor. MD simulations suggest that cinnamic acid, thymoquinone, and andrographolide (Kalmegh) could efficiently activate the biological pathway without changing the conformation in the binding site of the ACE2 receptor. The bioactivity and drug-likeness properties of compounds show their better pharmacological property and safer to use. INTERPRETATION & CONCLUSIONS: The study concludes the high potential of cinnamic acid, thymoquinone, and andrographolide against the SARS-CoV-2 ACE2 receptor protein. Thus, the molecular docking and MD simulation study will aid in understanding the molecular interaction between ligand and receptor binding site, thereby leading to novel therapeutic intervention.