scholarly journals Analysis of SARS-CoV-2 RNA-dependent RNA polymerase as a potential therapeutic drug target using a computational approach

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Syed Ovais Aftab ◽  
Muhammad Zubair Ghouri ◽  
Muhammad Umer Masood ◽  
Zeshan Haider ◽  
Zulqurnain Khan ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Drug Target ◽  
Computational Approach ◽  
Therapeutic Drug ◽  
Rna Dependent Rna Polymerase

scholarly journals A computational approach to drug repurposing against SARS-CoV-2 RNA dependent RNA polymerase (RdRp)

2020 ◽  
pp. 1-8 ◽  
Author(s):  
Giovanni Ribaudo ◽  
Alberto Ongaro ◽  
Erika Oselladore ◽  
Giuseppe Zagotto ◽  
Maurizio Memo ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Drug Repurposing ◽  
Computational Approach ◽  
Rna Dependent Rna Polymerase

scholarly journals A Fluorescence-Based Alkaline Phosphatase–Coupled Polymerase Assay for Identification of Inhibitors of Dengue Virus RNA-Dependent RNA Polymerase

2011 ◽  
Vol 16 (2) ◽  
pp. 201-210 ◽  
Author(s):  
Pornwaratt Niyomrattanakit ◽  
Siti Nurdiana Abas ◽  
Chin Chin Lim ◽  
David Beer ◽  
Pei-Yong Shi ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Dengue Virus ◽  
Rna Polymerase ◽  
High Throughput Screening ◽  
Drug Target ◽  
Rna Dependent Rna Polymerase ◽  
Signal Stability ◽  
Nucleotide Analogue ◽  
Virus Rna ◽  
Adenosine Nucleotide

The flaviviral RNA-dependent RNA polymerase (RdRp) is an attractive drug target. To discover new inhibitors of dengue virus RdRp, the authors have developed a fluorescence-based alkaline phosphatase–coupled polymerase assay (FAPA) for high-throughput screening (HTS). A modified nucleotide analogue (2′-[2-benzothiazoyl]-6′-hydroxybenzothiazole) conjugated adenosine triphosphate (BBT-ATP) and 3′UTR-U30 RNA were used as substrates. After the polymerase reaction, treatment with alkaline phosphatase liberates the BBT fluorophore from the polymerase reaction by-product, BBTPPi, which can be detected at excitation and emission wavelengths of 422 and 566 nm, respectively. The assay was evaluated by examining the time dependency, assay reagent effects, reaction kinetics, and signal stability and was validated with 3′dATP and an adenosine-nucleotide triphosphate inhibitor, giving IC50 values of 0.13 µM and 0.01 µM, respectively. A pilot screen of a diverse compound library of 40,572 compounds at 20 µM demonstrated good performance with an average Z factor of 0.81. The versatility and robustness of FAPA were evaluated with another substrate system, BBT-GTP paired with 3′UTR-C30 RNA. The FAPA method presented here can be readily adapted for other nucleotide-dependent enzymes that generate PPi.

scholarly journals Ivermectin as a promising RNA-dependent RNA polymerase inhibitor and a therapeutic drug against SARS-CoV2: Evidence from in silico studies

2020 ◽  
Author(s):  
Ananta Swargiary
Keyword(s):  
Rna Polymerase ◽  
3D Structure ◽  
Antiviral Drug ◽  
Strong Interactions ◽  
Therapeutic Drug ◽  
Binding Property ◽  
Binding Interaction ◽  
Rna Dependent Rna Polymerase ◽  
Potential Inhibitor ◽  
In Silico Studies

Abstract Purpose: COVID-19, caused by SARS-CoV2 virus is a contagious disease affecting millions of lives throughout the globe. Currently, there are no clinically approved drugs for SARS-CoV2 although some drugs are undergoing clinical trials. The present study investigates the binding property of ivermectin on four important drug targets, spike protein, RNA-dependent RNA polymerase, 3-chymotrypsin- and papain-like proteases of SARS-CoV2. Methods: The 3D structure of ivermectin along with known antiviral drug lopinavir, simeprevir and four nucleotides ATP, GTP, CTP, and UTP were downloaded from PubChem database. Crystal structures of proteins were downloaded from PDB database. PDB files were converted into pdbqt file using AutoDock tools. After proper processing and grid formation, docking was carried out in AutoDock vina. Furthermore, the co-crystallized RNA and its binding interactions with RdRp were studied using various visualization tools including Discovery studio.Results: Docking study showed that ivermectin is the best binding drug compared to lopinavir and simeprevir. The best binding interaction was found to be -9.7kcal/mol with RdRp suggesting potential inhibitor of the protein. Twenty-one amino acid residues of RdRp were found to interact with ivermectin including the catalytic residue Asp760. Furthermore, RNA-RdRp complex revealed that the catalytic active residues Ser759 and Asp760 of RdRp formed strong interactions with RNA chain. Binding of ivermectin in the active site of RdRp make clash with the nucleotides of RNA chain suggesting the possible inhibition of replication.Conclusions: The present study suggests ivermectin as a potential inhibitor of RdRp which may be crucial to combat the SARS-CoV2.

scholarly journals Structure of RNA-dependent RNA polymerase from 2019-nCoV, a major antiviral drug target

2020 ◽  
Author(s):  
Yan Gao ◽  
Liming Yan ◽  
Yucen Huang ◽  
Fengjiang Liu ◽  
Yao Zhao ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Drug Target ◽  
Antiviral Drug ◽  
Central Component ◽  
Rna Dependent Rna Polymerase ◽  
Transcription Machinery ◽  
Global Pandemic ◽  
Novel Coronavirus ◽  
Key Residues ◽  
Insight Into

AbstractA novel coronavirus (2019-nCoV) outbreak has caused a global pandemic resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase (RdRp, also named nsp12), which catalyzes the synthesis of viral RNA, is a key component of coronaviral replication/transcription machinery and appears to be a primary target for the antiviral drug, remdesivir. Here we report the cryo-EM structure of 2019-nCoV full-length nsp12 in complex with cofactors nsp7 and nsp8 at a resolution of 2.9-Å. Additional to the conserved architecture of the polymerase core of the viral polymerase family and a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain featured in coronaviral RdRp, nsp12 possesses a newly identified β-hairpin domain at its N-terminal. Key residues for viral replication and transcription are observed. A comparative analysis to show how remdesivir binds to this polymerase is also provided. This structure provides insight into the central component of coronaviral replication/transcription machinery and sheds light on the design of new antiviral therapeutics targeting viral RdRp.One Sentence SummaryStructure of 2019-nCov RNA polymerase.

scholarly journals STRUKTUR PROTEOMIK VIRUS DENGUE DAN MANFAATNYA SEBAGAI TARGET ANTIVIRUS

2015 ◽  
Vol 37 (2) ◽  
pp. 136
Author(s):  
Novia Rachmayanti
Keyword(s):  
Protein Structure ◽  
Rna Polymerase ◽  
Drug Target ◽  
Rna Dependent Rna Polymerase ◽  
Methyl Transferase ◽  
Ns3 Protease

AbstrakVirus dengue (DENV) telah menyebabkan sekitar 50 juta kasus infeksi demam berdarah setiap tahunnya, akan tetapi hingga saat ini belum terdapat vaksin maupun antivirus yang mampu mencegah atau mengobati penyakit tersebut. Selama pengembangan vaksin dan antivirus, diperoleh berbagai informasi tentang struktur protein DENV yang dapat dimanfaatkan sebagai target obat. Makalah membahas tentang struktur proteomik pada DENV, yaitu glikoprotein pada envelope, NS3 protease, NS3 helikase, NS5 metiltransferase, dan NS5 RNA-dependent RNA polimerase.AbstractDengue virus (DENV) has caused over 50 millions infection every year. However, to date neither vaccine nor medicine could be used to prevent or cure the illness. During researches in finding the vaccine or antiviral for DENV, information on DENV protein structure has been obtained which is potentially used as drug target. This paper disscuss DENV proteomic structure that consist of envelope glicoprotein, NS3 protease, NS3 helicase, NS5 methyl-transferase, and NS5 RNA-dependent RNA polymerase.

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