Abstract

A STUDY OF MULTI-TARGETED INHIBITOR PROTEINS USING in silico ANALYSIS

G. N. Nirmala* and Sandra Jose

ABSTRACT

The statistical records from 2020, World Health Organisation (WHO) disclosed Cancer among the top 10 leading death cause while, by 16th May 2020 there are more than 4 million COVID-19 patients. Pneumonia accounts for about 15% of deaths of children below 5 years, killing more than 8 million children in 2017.Drug repurposing is a novel approach of using a combination of drugs for a particular disease from pre-existing drugs which were found effective in treatment of certain others. Molecular docking helps to identify such molecules with potential inhibitory action and this paper deals with 33 proteins which were docked with octameric SARS-CoV main protease (M(Pro)), SARS-Coronavirus Non Structural Protein12 (NSP) bound to NSP7 and NSP8 co-factors and S. pneumoniae cell cycle regulator for their anti-microbial activities using Autodock4.2.6. The amount of Surface Area at the interface have a directly proportional relation with binding affinity and several studies showed that the hydrophobicity of the interacting protein molecule increases the selectivity of the binding domain. From this study, voltage-dependent potassium channelprotein was found to exhibit highest inhibitory activity (Binding energy: 16.8 Kcal/mole) against the targets and other 3 most effective proteins were Catalase, Pyocin tube PA0623 and Mytilin-B. These proteins were also analysed and studied based on their Hydrophobicity Indices (HP) and interface Surface Area (SA). The determined Interface SA and HPfor Kv interacting with the NSP of SARS CoV was the highest (1749Å2 and 1.47±0.66 respectively) which indicates a high binding affinity.

Keywords: Drug repurposing, inhibitory action, Molecular docking, SARS-CoV main protease, Voltage-dependent potassium channel, Hydrophobicity Indices.