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Drug Repurposing Approach Targeted Against Main Protease of SARS-CoV-2 Exploiting ‘Neighbourhood Behaviour’ in 3D Protein Structural Space and 2D Chemical Space of Small Molecules

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ChemRxiv
DOI
10.26434/chemrxiv.12057846.v1

The current global crisis due to COVID-19 has almost brought normal life to standstill in most parts of the world. With our research interest on repurposing known drugs/drug candidates targeting various diseases, we decided to analyse the available data on the deadly pathogen that has already taken thousands of lives since its outbreak in China in December 2019. Our host institute is now shutdown and we are confining ourselves to our homes with limited access to computational resources. Using a simple in silico approach based on the principle of ‘neighbourhood behaviour’ in three-dimensional (3D) space and two-dimensional (2D) space of protein and small molecules respectively, we have identified potential drugs/drug candidates which can be repurposed against protein targets encoded by the SARS-CoV-2 genome. Based on our preliminary analysis, we have so far prioritized more than 20 known drugs/drug candidates which might elucidate anti-coronavirus properties by binding to main protease of the pathogen. These drugs belong to diverse therapeutic areas such as antiviral, anticancer, antibacterial agents etc. Notably, apart from many synthetic molecules, our analysis also hints that phytochemicals obtained from vinca plant (vinca alkaloids) and camptotheca tree (camptothecin and its derivatives) have the potential to bind to main protease of SARS-CoV-2. In-depth investigation on our findings are currently on-going. Here we are presenting the results we obtained so far. The sole purpose of making these preliminary findings openly available to the community is for the experimental biologists and biomedical researchers to investigate our predictions in experimental set ups and for the clinicians to evaluate the potential of these findings for anti-COVID-19 treatment. Our findings should only be used for research purposes and we strongly urge that no individual should interpret these findings for any self-diagnosis or self-medication without the prior approval from competent international health/medical regulatory agencies.

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