scholarly journals Prediction of small molecule inhibitors targeting the novel coronavirus (SARS-CoV-2) RNA-dependent RNA polymerase

2020 ◽  
Author(s):  
Mohammed Ahmed ◽  
Abhisek Dwivedy ◽  
Richard Mariadasse ◽  
Satish Tiwari ◽  
Jeyaraman Jeyakanthan ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Small Molecules ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Viral Proteins ◽  
The Novel ◽  
Rna Dependent Rna Polymerase ◽  
Computational Tools ◽  
Gtp Binding ◽  
Novel Coronavirus

The current COVID-19 outbreak calls for a multi-disciplinary approach towards the design and development of novel anti-COVID therapeutics including vaccines and small molecule inhibitors targeting the viral proteins of causative agent, SARS-CoV-2. Using a combination of bioinformatics and computational tools, we have modelled the 3-D structure of the RNA-dependent RNA-polymerase (RdRp) of SARS-CoV-2 and predicted its probable GTP-binding site. This site was computationally targeted using small molecules inhibitors reported in a previous study on the RdRp of the Hepatitis C virus. Further optimizations have suggested a lead molecule that may prove fruitful in development of inhibitors against RdRp of SARS-CoV-2.

Screening of Kabasura Kudineer Chooranam against COVID-19 through Targeting of Main Protease and RNA-Dependent RNA Polymerase of SARS-CoV-2 by Molecular Docking Studies

2020 ◽  
Vol 5 (4) ◽  
pp. 319-331
Author(s):  
K. Gopalasatheeskumar ◽  
Karthikeyen Lakshmanan ◽  
Anguraj Moulishankar ◽  
Jerad Suresh ◽  
D. Kumuthaveni Babu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
Docking Studies ◽  
The Novel ◽  
Rna Dependent Rna Polymerase ◽  
Molecular Docking Studies ◽  
Main Protease ◽  
Short Span ◽  
Novel Coronavirus

COVID-19 is the infectious pandemic disease caused by the novel coronavirus. The COVID-19 is spread globally in a short span of time. The Ministry of AYUSH, India which promotes Siddha and other Indian system of medicine recommends the use of formulation like Nilavembu Kudineer and Kaba Sura Kudineer Chooranam (KSKC). The present work seeks to provide the evidence for the action of 74 different constituents of the KSKC formulation acting on two critical targets. That is main protease and SARS-CoV-2 RNAdependent RNA polymerase target through molecular docking studies. The molecular docking was done by using AutoDock Tools 1.5.6 of the 74 compounds, about 50 compounds yielded docking results against COVID-19 main protease while 42 compounds yielded against SARSCoV- 2 RNA-dependent RNA polymerase. This research has concluded that the KSKC has the lead molecules that inhibits COVID-19’s target of main protease of COVID-19 and SARS-CoV-2 RNA-dependent RNA polymerase.

scholarly journals Prediction of Small Molecule Inhibitors Targeting the Severe Acute Respiratory Syndrome Coronavirus-2 RNA-dependent RNA Polymerase

ACS Omega ◽  
2020 ◽  
Vol 5 (29) ◽  
pp. 18356-18366 ◽  
Author(s):  
Mohammed Ahmad ◽  
Abhisek Dwivedy ◽  
Richard Mariadasse ◽  
Satish Tiwari ◽  
Deepsikha Kar ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Rna Polymerase ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Rna Dependent Rna Polymerase

scholarly journals In silico evaluation of isatin-based derivatives with RNA-dependent RNA polymerase of the novel coronavirus SARS-CoV-2

2021 ◽  
pp. 1-16
Author(s):  
Rajesh Kumar M. ◽  
Daniel A. Gideon ◽  
Richard Mariadasse ◽  
Vijay Nirusimhan ◽  
Sherlin Rosita A. ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
In Silico ◽  
The Novel ◽  
Rna Dependent Rna Polymerase ◽  
Novel Coronavirus

scholarly journals Identification of Potent Small Molecule Inhibitors of SARS-CoV-2 Entry

2021 ◽  
Author(s):  
Sonia Jablonski ◽  
Huihui Mou ◽  
Yuka Otsuka ◽  
Joseph Jablonski ◽  
Robert S Adcock ◽  
...  
Keyword(s):  
Small Molecules ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Specific Inhibitor ◽  
Spike Protein ◽  
Target Cells ◽  
The Novel ◽  
Angiotensin Converting Enzyme 2 ◽  
Limited Effectiveness ◽  
Affinity Interaction

The severe acute respiratory syndrome coronavirus 2 responsible for COVID-19 remains a persistent threat to mankind, especially for the immunocompromised and elderly for which the vaccine may have limited effectiveness. Entry of SARS-CoV-2 requires a high affinity interaction of the viral spike protein with the cellular receptor angiotensin-converting enzyme 2. Novel mutations on the spike protein correlate with the high transmissibility of new variants of SARS-CoV-2, highlighting the need for small molecule inhibitors of virus entry into target cells. We report the identification of such inhibitors through a robust high-throughput screen testing 15,000 small molecules from unique libraries. Several leads were validated in a suite of mechanistic assays, including whole cell SARS-CoV-2 infectivity assays. The main lead compound, Calpeptin, was further characterized using SARS-CoV-1 and the novel SARS-CoV-2 variant entry assays, SARS-CoV-2 protease assays and molecular docking. This study reveals Calpeptin as a potent and specific inhibitor of SARS-CoV-2 and some variants.

scholarly journals In-Silico Computational Screening of Siddha formulations Visha Sura Kudineer and Adathodai Kudineer against RNA dependent RNA polymerase of SARS CoV-2

2021 ◽  
Vol 12 (3) ◽  
pp. 534-537
Author(s):  
Panneerselvam N R ◽  
Anbarasan B
Keyword(s):  
Rna Polymerase ◽  
In Silico ◽  
Viral Infections ◽  
Therapeutic Option ◽  
Docking Studies ◽  
The Novel ◽  
Rna Dependent Rna Polymerase ◽  
Computational Screening ◽  
Novel Coronavirus ◽  
Tract Infections

Background: Siddha Medicine is an important therapeutic option used for treating various respiratory viral infections and has antiviral herbs. Aim: The study aims to perform the In Silico computational studies of Phytoconstituents of Siddha formulation Visha Sura Kudineer and Adathodai Kudineer which are commonly used in the treatment of viral fever and respiratory tract infections and could be effective against the novel coronavirus disease. Methods: Autodock program was used for the molecular docking studies against RNA-dependent RNA polymerase (RdRP) (PDB ID: 6NUR). Results: A total of 9 compounds were screened, of these 4 compounds namely, Andrographolide of Visha Sura Kudineer and Anisotine, Apioside, and 1-(p-Methoxybenzoyl) aziridine of Adathodai Kudineer showed high binding affinity against RdRp. Conclusion: Based on further experiments and clinical trials, formulations Visha Sura Kudineer and Adathodai Kudineer could be effective in the treatment of COVID-19.

scholarly journals The Possible Origins of the Novel Coronavirus SARS-CoV-2

2020 ◽  
Author(s):  
Arun Shanker
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Rna Polymerase ◽  
Yunnan Province ◽  
The Novel ◽  
Rna Dependent Rna Polymerase ◽  
High Sequence Identity ◽  
Sequence Identity ◽  
Rhinolophus Affinis ◽  
Novel Coronavirus ◽  
Bat Coronavirus

Severe Acute Respiratory Syndrome (SARS) was seen as this century’s first Pandemic and was previously unknown. It was demonstrated that bats in the genus Rhinolophus are natural reservoirs of SARS-like viruses. Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) was seen in 2012, it was similar to SARS CoV and is phylogenetically closely related to the bat coronaviruses (BatCoVs) HKU4 and HKU5. SARS-CoV-2 was seen in Wuhan in 2019 and SARS-CoV-2 is thought to be transmitted from animals to humans. It originated in bats and probably got into an intermediate animal and then to humans. The virus could have used the intermediate animal to adapt to transmit to humans. It was seen that a short region of RNA-dependent RNA polymerase (RdRp) from a bat coronavirus (BatCoV RaTG13) which was previously detected in Rhinolophus affinis from Yunnan province showed high sequence identity to SARS-CoV-2. We discuss the possible origins of SARS-CoV-2 here and see that there are a lot of possibilities.

scholarly journals In silico evaluation of isatin-based derivatives with RNA-dependent RNA polymerase of the novel coronavirus SARS-CoV-2

2020 ◽  
Author(s):  
Rajesh Kumar M ◽  
Daniel Andrew Gideon ◽  
Richard Mariadasse ◽  
Vijay Nirusimhan ◽  
Sherlin Rosita. A ◽  
...  
Keyword(s):  
Binding Energy ◽  
Rna Polymerase ◽  
In Silico ◽  
Biological Activities ◽  
The Novel ◽  
Rna Dependent Rna Polymerase ◽  
Ligand Interactions ◽  
Novel Coronavirus ◽  
Site Binding ◽  
The Ideal

Isatin (1H-indole-2,3-dione)-containing compounds have been shown to possess several remarkable biological activities. We had previously explored a few isatin-based imidazole derivatives for their predicted dual activity against both inflammation and cancer. We explored 47 different isatin-based derivatives (IBDs) for other potential biological activities using in silico tools and found them to possess anti-viral activity. Using AUTODOCK tools, the binding site, binding energy, inhibitory constant/Ki and receptor-ligand interactions for each of the compounds was analyzed against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). The partition coefficient (logP) values were predicted using MedChem Designer tool. Based on the best Ki, binding energy and the ideal range of logP (between 1.0-3.0), 10 out of total 47 compounds were deemed to be prospective RdRp inhibitors. Some of these compounds gave better Ki, binding energy and logP values when compared to standard RdRp inhibitors such as remdesivir (Ki = 15.61 μM, logP = 2.2; binding energy = -6.95), a clinically approved RdRp inhibitor which is widely used for critical care of COVID-19 patients. The same in silico parameters were assessed for 9 other popular RdRp inhibitors (other than remdesivir), which were earlier used to target RdRp of other viruses, and are now repurposed to target SARS-CoV-2 RdRp. The results showed that the 10 selected isatin-based derivatives (IBDs) could be further explored for activity against SARS-Cov-2. In the present study we evaluated the efficacy of these compounds in silico.

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