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 Targeting SARS-CoV-2 RNA-dependent RNA polymerase: An in silico drug repurposing for COVID-19

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1166
Author(s):  
Krishnaprasad Baby ◽  
Swastika Maity ◽  
Chetan H. Mehta ◽  
Akhil Suresh ◽  
Usha Y. Nayak ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Active Site ◽  
In Silico ◽  
Drug Repurposing ◽  
Drug Binding ◽  
Rna Dependent Rna Polymerase ◽  
Target Proteins ◽  
Dynamics Simulations ◽  
Preclinical And Clinical Studies ◽  
And Control

Background: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), took more lives than combined epidemics of SARS, MERS, H1N1, and Ebola. Currently, the prevention and control of spread are the goals in COVID-19 management as there are no specific drugs to cure or vaccines available for prevention. Hence, the drug repurposing was explored by many research groups, and many target proteins have been examined. The major protease (Mpro), and RNA-dependent RNA polymerase (RdRp) are two target proteins in SARS-CoV-2 that have been validated and extensively studied for drug development in COVID-19. The RdRp shares a high degree of homology between those of two previously known coronaviruses, SARS-CoV and MERS-CoV. Methods: In this study, the FDA approved library of drugs were docked against the active site of RdRp using Schrodinger's computer-aided drug discovery tools for in silico drug-repurposing. Results: We have shortlisted 14 drugs from the Standard Precision docking and interaction-wise study of drug-binding with the active site on the enzyme. These drugs are antibiotics, NSAIDs, hypolipidemic, coagulant, thrombolytic, and anti-allergics. In molecular dynamics simulations, pitavastatin, ridogrel and rosoxacin displayed superior binding with the active site through ARG555 and divalent magnesium. Conclusion: Pitavastatin, ridogrel and rosoxacin can be further optimized in preclinical and clinical studies to determine their possible role in COVID-19 treatment.

scholarly journals SARS-CoV-2 RNA Dependent RNA polymerase (RdRp) – A drug repurposing study

Heliyon ◽  
2020 ◽  
Vol 6 (7) ◽  
pp. e04502 ◽  
Author(s):  
Jamshaid Ahmad ◽  
Saima Ikram ◽  
Fawad Ahmad ◽  
Irshad Ur Rehman ◽  
Maryam Mushtaq
Keyword(s):  
Rna Polymerase ◽  
Drug Repurposing ◽  
Rna Dependent Rna Polymerase

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

Repurposing Nonnucleoside Antivirals Against SARS-CoV2 NSP12 (RNA Dependent RNA Polymerase) and Identification of Domain Specific Interactions

2020 ◽  
Author(s):  
Feroza Begum ◽  
UPASANA RAY
Keyword(s):  
Rna Polymerase ◽  
Particle Production ◽  
Drug Repurposing ◽  
Viral Rna ◽  
Rna Dependent Rna Polymerase ◽  
Domain Specific ◽  
Virus Rna ◽  
Promising Area ◽  
Screening And Identification ◽  
Approved Drugs

<p>The pandemic of SARS-CoV-2 has necessitated expedited research efforts towards finding potential antiviral targets and drug development measures. While new drug discovery is time consuming, drug repurposing has been a promising area for elaborate virtual screening and identification of existing FDA approved drugs that could possibly be used for targeting against functions of various proteins of SARS-CoV-2 virus. RNA dependent RNA polymerase (RdRp) is an important enzyme for the virus that mediates replication of the viral RNA. Inhibition of RdRp could inhibit viral RNA replication and thus new virus particle production. Here, we screened non-nucleoside antivirals and found three out of them to be strongest in binding to RdRp. We propose these three drugs as potential RdRp inhibitors based on the site of binding. </p>

scholarly journals Repurposing Nonnucleoside Antivirals Against SARS-CoV2 NSP12 (RNA Dependent RNA Polymerase) and Identification of Domain Specific Interactions

2020 ◽  
Author(s):  
Feroza Begum ◽  
UPASANA RAY
Keyword(s):  
Rna Polymerase ◽  
Particle Production ◽  
Drug Repurposing ◽  
Viral Rna ◽  
Rna Dependent Rna Polymerase ◽  
Domain Specific ◽  
Virus Rna ◽  
Promising Area ◽  
Screening And Identification ◽  
Approved Drugs

<p>The pandemic of SARS-CoV-2 has necessitated expedited research efforts towards finding potential antiviral targets and drug development measures. While new drug discovery is time consuming, drug repurposing has been a promising area for elaborate virtual screening and identification of existing FDA approved drugs that could possibly be used for targeting against functions of various proteins of SARS-CoV-2 virus. RNA dependent RNA polymerase (RdRp) is an important enzyme for the virus that mediates replication of the viral RNA. Inhibition of RdRp could inhibit viral RNA replication and thus new virus particle production. Here, we screened non-nucleoside antivirals and found three out of them to be strongest in binding to RdRp. We propose these three drugs as potential RdRp inhibitors based on the site of binding. </p>

scholarly journals Raltegravir, Indinavir, Tipranavir, Dolutegravir, and Etravirine against main protease and RNA-dependent RNA polymerase of SARS-CoV-2: A molecular docking and drug repurposing approach

2020 ◽  
Vol 13 (12) ◽  
pp. 1856-1861
Author(s):  
Purushothaman Indu ◽  
Marimuthu Ragavan Rameshkumar ◽  
Narasingam Arunagirinathan ◽  
Naif Abdullah Al-Dhabi ◽  
Mariadhas Valan Arasu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
Drug Repurposing ◽  
Rna Dependent Rna Polymerase ◽  
Main Protease

scholarly journals Natural plant products as potential inhibitors of RNA dependent RNA polymerase of Severe Acute Respiratory Syndrome Coronavirus-2

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251801
Author(s):  
Shruti Koulgi ◽  
Vinod Jani ◽  
Mallikarjunachari Uppuladinne V. N. ◽  
Uddhavesh Sonavane ◽  
Rajendra Joshi
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Rna Polymerase ◽  
Conformational Changes ◽  
Drug Repurposing ◽  
Principal Component ◽  
Salt Bridge ◽  
Potential Effect ◽  
Tinospora Cordifolia ◽  
Rna Dependent Rna Polymerase ◽  
Dynamics Simulations

Drug repurposing studies targeting inhibition of RNA dependent RNA polymerase (RdRP) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have exhibited the potential effect of small molecules. In the present work a detailed interaction study between the phytochemicals from Indian medicinal plants and the RdRP of SARS-CoV-2 has been performed. The top four phytochemicals obtained through molecular docking were, swertiapuniside, cordifolide A, sitoindoside IX, and amarogentin belonging to Swertia chirayita, Tinospora cordifolia and Withania somnifera. These ligands bound to the RdRP were further studied using molecular dynamics simulations. The principal component analysis of these systems showed significant conformational changes in the finger and thumb subdomain of the RdRP. Hydrogen bonding, salt-bridge and water mediated interactions supported by MM-GBSA free energy of binding revealed strong binding of cordifolide A and sitoindoside IX to RdRP. The ligand-interacting residues belonged to either of the seven conserved motifs of the RdRP. These residues were polar and charged amino acids, namely, ARG 553, ARG 555, ASP 618, ASP 760, ASP 761, GLU 811, and SER 814. The glycosidic moieties of the phytochemicals were observed to form favourable interactions with these residues. Hence, these phytochemicals may hold the potential to act as RdRP inhibitors owing to their stability in binding to the druggable site.

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