Abstract
The hunt for potential lead/drug molecules from different resources, especially from natural resources, for possible treatment of COVID-19 is ongoing. Several compounds have already been identified, but only a few are good enough to show potential against the virus. Among the identified druggable target proteins of SARS-CoV-2, this study focuses on non-structural RNA-dependent RNA polymerase protein (RdRp), a well-known enzyme for both viral genome replication and viral mRNA synthesis, and is therefore considered to be the primary target. In this study, the virtual screening followed by an in-depth docking study of the Compounds Library found that natural compound Cyclocurcumin and Silybin B have strong interaction with RdRp and much better than the remdesivir with free binding energy and inhibition constant value as ꞌ-6.29 kcal/mol and 58.39 µMꞌ, and ꞌ-7.93kcal/mol and 45.3 µMꞌ, respectively. The finding indicated that the selected hits (Cyclocurcumin and Silybin B) could act as non-nucleotide anti-polymerase agents, and can be further optimized as a potential inhibitor of RdRp by benchwork experiments.
MeSH terms
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Adenosine Monophosphate / analogs & derivatives*
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Adenosine Monophosphate / chemistry
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Adenosine Monophosphate / metabolism
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Alanine / analogs & derivatives*
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Alanine / chemistry
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Alanine / metabolism
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Antiviral Agents / chemistry
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Antiviral Agents / metabolism*
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Biological Products / chemistry
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Biological Products / metabolism*
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COVID-19 / metabolism*
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COVID-19 / virology
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Catalytic Domain
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Coronavirus RNA-Dependent RNA Polymerase / antagonists & inhibitors
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Coronavirus RNA-Dependent RNA Polymerase / chemistry
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Coronavirus RNA-Dependent RNA Polymerase / metabolism*
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Curcumin / analogs & derivatives
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Curcumin / chemistry
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Curcumin / metabolism
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Databases, Protein
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Drug Discovery / methods*
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Drug Evaluation, Preclinical / methods
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Humans
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Hydrogen Bonding
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Hydrophobic and Hydrophilic Interactions
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Molecular Docking Simulation / methods*
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Phytochemicals / chemistry
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Phytochemicals / metabolism*
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Protein Binding
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SARS-CoV-2 / enzymology*
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Silybin / chemistry
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Silybin / metabolism
Substances
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Antiviral Agents
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Biological Products
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Phytochemicals
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remdesivir
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Adenosine Monophosphate
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Silybin
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Coronavirus RNA-Dependent RNA Polymerase
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NSP12 protein, SARS-CoV-2
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Curcumin
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Alanine