Prediction of Potential Inhibitors for SARS CoV- 2 Using Comprehensive Drug Repurposing and Molecular Docking Approach

Prof. (Dr). Senthilraja. M 1

8th WCPSDM.2021. APR.Published Online 18 APR 2021

Abstract : COVID-19 has now been declared as pandemic and new treatments are urgently needed as we enter a phase beyond containment. Developing new drugs from scratch is a lengthy process, thus impractical to face the immediate global challenge. Drug repurposing is an emerging strategy where existing medicines, having already been tested safe in humans, are redeployed to combat difficult-to-treat diseases. While using such repurposed drugs individually may ultimately not yield a significant clinical benefit, carefully combined cocktails could be very effective, as was for HIV in the 1990s; Here, comprehensive computational approaches including drug repurposing and molecular docking are employed to predict an effective drug candidate targeting RdRp of SARS-CoV-2.The virus has spread to more than 38 countries around the world. However, the drug has not yet been officially licensed or approved to treat SARS- Cov-2 infection. NSP12-NSP7 complex of SARS-CoV-2 is essential for viral replication and transcription is generally regarded as a potential target to fight against the virus. According to the NSP12-NSP7 complex (PDB ID: 6NUR) structure of SARS, the following homologous models were established for virtual screening in present study, namely NSP12-NSP7 interface model. In this study the following drugs such as, Umifenovir, Fidaxomicin, Raltegravir, Delavirdine, Gemcitabine hydrochloride revealed that may have a potential inhibitory interaction with RdRp of SARS-CoV-2 and could be effective drugs for COVID-19. These were selected for binding free energy calculations based on virtual screening and docking scores. All five compounds can combine well with NSP12-NSP7 in the homologous model. In addition, virtual screening of the compounds from ZINC database ZINC09128257 and ZINC09883358 also allowed for the prediction with pharmacophore features that interact effectively with RdRp of SARS-CoV-2; indicating their potentiality as effective inhibitors of the enzyme.