Revealing the Inhibition Mechanism of RNA-Dependent RNA Polymerase (RdRp) of SARS-CoV-2 by Remdesivir and Nucleotide Analogues: A Molecular Dynamics Simulation Study

2020 ◽  
Vol 124 (47) ◽  
pp. 10641-10652 ◽  
Author(s):  
Padmaja D. Wakchaure ◽  
Shibaji Ghosh ◽  
Bishwajit Ganguly
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Rna Polymerase ◽  
Simulation Study ◽  
Dynamics Simulation ◽  
Inhibition Mechanism ◽  
Rna Dependent Rna Polymerase ◽  
Nucleotide Analogues

scholarly journals Discovery of Potential Compounds Against SARS-COV-2 Based on 3clpro/Rdrp Dual-Target an in Silico Approach

2021 ◽  
Author(s):  
Jiaojiao Li ◽  
Lin Zhu ◽  
Zheng Qin ◽  
Zhengfu Li ◽  
Xun Gao ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Virtual Screening ◽  
Severe Acute Respiratory Syndrome ◽  
Rna Polymerase ◽  
Dynamics Simulation ◽  
Rna Dependent Rna Polymerase ◽  
Simulation Results ◽  
Dual Target

Abstract Currently, Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) lacks clinically specific drugs. In this study, the new coronavirus SARS-CoV-2 3-chymotrypsin-like protease(3CLpro)and RNA-dependent RNA polymerase(RdRp)were used as targets for virtual screening. After analysis of molecular docking and molecular dynamics simulation results, ZINC04259665,ZINC12659533 and ZINC70705490 have good docking scores,and they are stable in combination with 3CLpro/RdRp. The prediction of drug-like properties found that ZINC04259665 has good druggability and has the potential to further explore its anti-SARS-CoV-2.

scholarly journals Discovering Potential RNA Dependent RNA Polymerase Inhibitors as Prospective Drugs Against COVID-19: An in silico Approach

2021 ◽  
Vol 12 ◽  
Author(s):  
Satabdi Saha ◽  
Rajat Nandi ◽  
Poonam Vishwakarma ◽  
Amresh Prakash ◽  
Diwakar Kumar
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Rna Polymerase ◽  
Binding Affinity ◽  
Epigallocatechin Gallate ◽  
Docking Study ◽  
Dynamics Simulation ◽  
Rna Dependent Rna Polymerase ◽  
Inhibitory Potential ◽  
New Treatment

COVID-19, caused by Severe Acute Respiratory Syndrome Corona Virus 2, is declared a Global Pandemic by WHO in early 2020. In the present situation, though more than 180 vaccine candidates with some already approved for emergency use, are currently in development against SARS-CoV-2, their safety and efficacy data is still in a very preliminary stage to recognize them as a new treatment, which demands an utmost emergency for the development of an alternative anti-COVID-19 drug sine qua non for a COVID-19 free world. Since RNA-dependent RNA polymerase (RdRp) is an essential protein involved in replicating the virus, it can be held as a potential drug target. We were keen to explore the plant-based product against RdRp and analyze its inhibitory potential to treat COVID-19. A unique collection of 248 plant compounds were selected based on their antiviral activity published in previous literature and were subjected to molecular docking analysis against the catalytic sub-unit of RdRp. The docking study was followed by a pharmacokinetics analysis and molecular dynamics simulation study of the selected best-docked compounds. Tellimagrandin I, SaikosaponinB2, Hesperidin and (-)-Epigallocatechin Gallate were the most prominent ones that showed strong binding affinity toward RdRp. All the compounds mentioned showed satisfactory pharmacokinetics properties and remained stabilized at their respective binding sites during the Molecular dynamics simulation. Additionally, we calculated the free-binding energy/the binding properties of RdRp-ligand complexes with the connection of MM/GBSA. Interestingly, we observe that SaikosaponinB2 gives the best binding affinity (∆Gbinding = −42.43 kcal/mol) in the MM/GBSA assay. Whereas, least activity is observed for Hesperidin (∆Gbinding = −22.72 kcal/mol). Overall our study unveiled the feasibility of the SaikosaponinB2 to serve as potential molecules for developing an effective therapy against COVID-19 by inhibiting one of its most crucial replication proteins, RdRp.

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