Screening of Severe Acute Respiratory Syndrome Coronavirus 2 RNA-Dependent RNA Polymerase Inhibitors Using Computational Approach

2021 ◽  
Author(s):  
Poonam Dhankhar ◽  
Vikram Dalal ◽  
Viney Kumar
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Rna Polymerase ◽  
Computational Approach ◽  
Rna Dependent Rna Polymerase ◽  
Polymerase Inhibitors

scholarly journals Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency

2020 ◽  
Vol 295 (20) ◽  
pp. 6785-6797 ◽  
Author(s):  
Calvin J. Gordon ◽  
Egor P. Tchesnokov ◽  
Emma Woolner ◽  
Jason K. Perry ◽  
Joy Y. Feng ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Rna Polymerase ◽  
Rna Synthesis ◽  
Ebola Virus ◽  
Lassa Virus ◽  
Nonstructural Proteins ◽  
Rna Dependent Rna Polymerase ◽  
Direct Acting Antiviral ◽  
Nucleotide Analogue ◽  
Direct Acting

Effective treatments for coronavirus disease 2019 (COVID-19) are urgently needed to control this current pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Replication of SARS-CoV-2 depends on the viral RNA-dependent RNA polymerase (RdRp), which is the likely target of the investigational nucleotide analogue remdesivir (RDV). RDV shows broad-spectrum antiviral activity against RNA viruses, and previous studies with RdRps from Ebola virus and Middle East respiratory syndrome coronavirus (MERS-CoV) have revealed that delayed chain termination is RDV's plausible mechanism of action. Here, we expressed and purified active SARS-CoV-2 RdRp composed of the nonstructural proteins nsp8 and nsp12. Enzyme kinetics indicated that this RdRp efficiently incorporates the active triphosphate form of RDV (RDV-TP) into RNA. Incorporation of RDV-TP at position i caused termination of RNA synthesis at position i+3. We obtained almost identical results with SARS-CoV, MERS-CoV, and SARS-CoV-2 RdRps. A unique property of RDV-TP is its high selectivity over incorporation of its natural nucleotide counterpart ATP. In this regard, the triphosphate forms of 2′-C-methylated compounds, including sofosbuvir, approved for the management of hepatitis C virus infection, and the broad-acting antivirals favipiravir and ribavirin, exhibited significant deficits. Furthermore, we provide evidence for the target specificity of RDV, as RDV-TP was less efficiently incorporated by the distantly related Lassa virus RdRp, and termination of RNA synthesis was not observed. These results collectively provide a unifying, refined mechanism of RDV-mediated RNA synthesis inhibition in coronaviruses and define this nucleotide analogue as a direct-acting antiviral.

Identification and characterization of Zika virus NS5 RNA-dependent RNA polymerase inhibitors

2019 ◽  
Vol 54 (4) ◽  
pp. 502-506 ◽  
Author(s):  
Yuan Lin ◽  
Hongjuan Zhang ◽  
Weibao Song ◽  
Shuyi Si ◽  
Yanxing Han ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Zika Virus ◽  
Rna Dependent Rna Polymerase ◽  
Polymerase Inhibitors ◽  
Identification And Characterization

HCV NS5b RNA-Dependent RNA Polymerase Inhibitors:  From α,γ-Diketoacids to 4,5-Dihydroxypyrimidine- or 3-Methyl-5- hydroxypyrimidinonecarboxylic Acids. Design and Synthesis

2004 ◽  
Vol 47 (22) ◽  
pp. 5336-5339 ◽  
Author(s):  
Vincenzo Summa ◽  
Alessia Petrocchi ◽  
Victor G. Matassa ◽  
Marina Taliani ◽  
Ralph Laufer ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Dependent Rna Polymerase ◽  
Design And Synthesis ◽  
Polymerase Inhibitors ◽  
Hcv Ns5b

Phenyldihydroxypyrimidines as HCV NS5B RNA Dependent RNA Polymerase Inhibitors. Part II: Sulfonamides

2005 ◽  
Vol 2 (6) ◽  
pp. 456-461 ◽  
Author(s):  
S. Ponzi ◽  
C. Giuliano ◽  
M. Donghi ◽  
M. Poma ◽  
V. Matassa ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Dependent Rna Polymerase ◽  
Polymerase Inhibitors ◽  
Hcv Ns5b

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
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