scholarly journals Remdesivir Strongly Binds to both RNA-dependent RNA Polymerase and Main Protease of SARS-CoV-2: Evidence from Molecular Simulations

2020 ◽  
Author(s):  
Hoang Linh Nguyen ◽  
Thai Nguyen ◽  
Duc Toan Truong ◽  
Mai Suan Li
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Rna Polymerase ◽  
Binding Affinity ◽  
Recent Experiment ◽  
Umbrella Sampling ◽  
Rna Dependent Rna Polymerase ◽  
Main Protease ◽  
The World ◽  
Binding Mechanisms

The outbreak of a new coronavirus SARS-CoV-2 (severe acute respiratory syndrome–<br>coronavirus 2) has caused a global CoVid-19 (coronavirus disease 2019) pandemic, resulting in millions of infections and thousands of deaths around the world. There is currently no drug or vaccine for CoVid-19, but it has been revealed that some commercially available drugs are promising, at least for treating symptoms. Among them, Remdesivir, which can block the activity of RNA-dependent RNA polymerase (RdRp) in old SARS-CoV and MERS-CoV viruses, has been prescribed to CoVid-19 patients in many countries. A recent experiment showed that Remdesivir binds to SARS-CoV-2 with an inhibition constant of μM, but the exact target has not been reported. In this work, combining molecular docking, steered molecular dynamics and umbrella sampling we examined its binding affinity to two targets including the main protease (Mpro), also known as 3C-like protease, and RdRp. We showed that Remdesivir binds to Mpro slightly weaker than to RdRp and the corresponding inhibition constants, consistent with the experiment, fall to the μM range. The binding mechanisms of<br>Remdesivir to two targets differ in that electrostatic interaction is the main force in stabilizing the RdRp-Remdesivir complex, while the van der Waals interaction dominates in the MproRemdesivir case. Our result indicates that Remdesivir can target not only RdRp but also Mpro, which can be invoked to explain why this drug is effective in treating Covid-19. We have identified residues of the target protein that make the most important contribution to binding affinity, and this information is useful for drug development for this disease. <br>

scholarly journals Remdesivir Strongly Binds to both RNA-dependent RNA Polymerase and Main Protease of SARS-CoV-2: Evidence from Molecular Simulations

2020 ◽  
Author(s):  
Hoang Linh Nguyen ◽  
Thai Nguyen ◽  
Duc Toan Truong ◽  
Mai Suan Li
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Rna Polymerase ◽  
Binding Affinity ◽  
Recent Experiment ◽  
Umbrella Sampling ◽  
Rna Dependent Rna Polymerase ◽  
Main Protease ◽  
The World ◽  
Binding Mechanisms

The outbreak of a new coronavirus SARS-CoV-2 (severe acute respiratory syndrome–<br>coronavirus 2) has caused a global CoVid-19 (coronavirus disease 2019) pandemic, resulting in millions of infections and thousands of deaths around the world. There is currently no drug or vaccine for CoVid-19, but it has been revealed that some commercially available drugs are promising, at least for treating symptoms. Among them, Remdesivir, which can block the activity of RNA-dependent RNA polymerase (RdRp) in old SARS-CoV and MERS-CoV viruses, has been prescribed to CoVid-19 patients in many countries. A recent experiment showed that Remdesivir binds to SARS-CoV-2 with an inhibition constant of μM, but the exact target has not been reported. In this work, combining molecular docking, steered molecular dynamics and umbrella sampling we examined its binding affinity to two targets including the main protease (Mpro), also known as 3C-like protease, and RdRp. We showed that Remdesivir binds to Mpro slightly weaker than to RdRp and the corresponding inhibition constants, consistent with the experiment, fall to the μM range. The binding mechanisms of<br>Remdesivir to two targets differ in that electrostatic interaction is the main force in stabilizing the RdRp-Remdesivir complex, while the van der Waals interaction dominates in the MproRemdesivir case. Our result indicates that Remdesivir can target not only RdRp but also Mpro, which can be invoked to explain why this drug is effective in treating Covid-19. We have identified residues of the target protein that make the most important contribution to binding affinity, and this information is useful for drug development for this disease. <br>

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 Molecular Docking Unmasks Potent Phytoligands against SARS CoV 2 Spike Glycoprotein, Main Protease, Papain like Protease and RNA dependent RNA Polymerase

2020 ◽  
Vol 5 (4) ◽  
pp. 255-267
Author(s):  
Priyanka Dhar ◽  
Paushali Roy
Keyword(s):  
Molecular Docking ◽  
Oleic Acid ◽  
Rna Polymerase ◽  
Hydrophobic Interactions ◽  
Spike Glycoprotein ◽  
Rna Dependent Rna Polymerase ◽  
Ligand Interaction ◽  
Unique Challenge ◽  
Main Protease ◽  
Inhibitory Potential

The recent coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has offered a unique challenge for human survival. However, there is no available known prophylaxis, therapeutic intervention, and vaccine candidate against SARS-CoV-2 to date. We aimed towards identifying novel phytoligands from widely available botanical resources which could serve as potential inhibitors against SARS-CoV-2. Based on literature review, database search, ADMET, and drug-likeness, 55 phytoligands and 8 synthetic repurposing drugs were screened and tested against SARS-CoV-2 spike glycoprotein, main protease, papain-like protease, and RNA-dependent RNA polymerase using molecular docking and protein-ligand interaction. All phytoligands and repurposing drugs showed binding affinity based inhibitory potential against the viral proteins. The highest binding affinities of phytoligands towards antiviral targets were exhibited by colchicine and oleic acid, and that of repurposing drugs was shown by saquinavir and nelfinavir. Capsaicin, oleic acid, azithromycin, nelfinavir, remdesivir, and saquinavir were acted as plausible broad-spectrum inhibitors. Hydrogen bonds and hydrophobic interactions of amino acids were varied significantly within the conserved domain along with glutamic acid richness. Further investigation should be carried out to obtain the synergistic effect using cell-based assays, animal models, and clinical trials to discover novel phytomedicine against SARS-CoV-2.

scholarly journals Discovery of Potential Compounds Against SARS-COV-2 Based on 3clpro/Rdrp Dual-Target an in Silico Approach

2021 ◽  
Author(s):  
Jiaojiao Li ◽  
Lin Zhu ◽  
Zheng Qin ◽  
Zhengfu Li ◽  
Xun Gao ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Virtual Screening ◽  
Severe Acute Respiratory Syndrome ◽  
Rna Polymerase ◽  
Dynamics Simulation ◽  
Rna Dependent Rna Polymerase ◽  
Simulation Results ◽  
Dual Target

Abstract Currently, Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) lacks clinically specific drugs. In this study, the new coronavirus SARS-CoV-2 3-chymotrypsin-like protease(3CLpro)and RNA-dependent RNA polymerase(RdRp)were used as targets for virtual screening. After analysis of molecular docking and molecular dynamics simulation results, ZINC04259665,ZINC12659533 and ZINC70705490 have good docking scores,and they are stable in combination with 3CLpro/RdRp. The prediction of drug-like properties found that ZINC04259665 has good druggability and has the potential to further explore its anti-SARS-CoV-2.

scholarly journals Computational selection of flavonoid compounds as inhibitors against SARS-CoV-2 main protease, RNA-dependent RNA polymerase and spike proteins: A molecular docking study

2021 ◽  
Vol 28 (1) ◽  
pp. 448-458
Author(s):  
Marimuthu Ragavan Rameshkumar ◽  
Purushothaman Indu ◽  
Narasingam Arunagirinathan ◽  
Babu Venkatadri ◽  
Hamed A. El-Serehy ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Rna Dependent Rna Polymerase ◽  
Flavonoid Compounds ◽  
Main Protease ◽  
Selection Of ◽  
Spike Proteins

scholarly journals Alkaloids from Cryptolepis sanguinolenta as Potential Inhibitors of SARS-CoV-2 Viral Proteins: An In Silico Study

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Lawrence Sheringham Borquaye ◽  
Edward Ntim Gasu ◽  
Gilbert Boadu Ampomah ◽  
Lois Kwane Kyei ◽  
Margaret Amerley Amarh ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Rna Polymerase ◽  
In Silico ◽  
Viral Proteins ◽  
Binding Energies ◽  
New Drugs ◽  
Binding Potential ◽  
Rna Dependent Rna Polymerase ◽  
Cryptolepis Sanguinolenta ◽  
Main Protease

The ongoing global pandemic caused by the human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions of people and claimed hundreds of thousands of lives. The absence of approved therapeutics to combat this disease threatens the health of all persons on earth and could cause catastrophic damage to society. New drugs are therefore urgently required to bring relief to people everywhere. In addition to repurposing existing drugs, natural products provide an interesting alternative due to their widespread use in all cultures of the world. In this study, alkaloids from Cryptolepis sanguinolenta have been investigated for their ability to inhibit two of the main proteins in SARS-CoV-2, the main protease and the RNA-dependent RNA polymerase, using in silico methods. Molecular docking was used to assess binding potential of the alkaloids to the viral proteins whereas molecular dynamics was used to evaluate stability of the binding event. The results of the study indicate that all 13 alkaloids bind strongly to the main protease and RNA-dependent RNA polymerase with binding energies ranging from -6.7 to -10.6 kcal/mol. In particular, cryptomisrine, cryptospirolepine, cryptoquindoline, and biscryptolepine exhibited very strong inhibitory potential towards both proteins. Results from the molecular dynamics study revealed that a stable protein-ligand complex is formed upon binding. Alkaloids from Cryptolepis sanguinolenta therefore represent a promising class of compounds that could serve as lead compounds in the search for a cure for the corona virus disease.

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
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