scholarly journals Potential Therapeutic Agents for COVID-19 Based on the Analysis of Protease and RNA Polymerase Docking

2020 ◽  
Author(s):  
Yu-Chuan Chang ◽  
Yi-An Tung ◽  
Ko-Han Lee ◽  
Ting-Fu Chen ◽  
Yu-Chun Hsiao ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Active Sites ◽  
Therapeutic Agents ◽  
Hiv Protease ◽  
Hiv Protease Inhibitors ◽  
Docking Site ◽  
Autodock Vina ◽  
Nucleotide Analogues ◽  
Novel Coronavirus ◽  
Protein Pocket

The outbreak of novel coronavirus (COVID-19) infections occurring in 2019 is in dire need of finding potential therapeutic agents. In this study, we used molecular docking strategies to repurpose HIV protease inhibitors and nucleotide analogues for COVID-19. The evaluation was made on docking scores calculated by AutoDock Vina and RosettaCommons. Preliminary results suggested that Indinavir and Remdesivir have the best docking scores and the comparison of the docking sites of these two drugs shows a near perfect dock in the overlap region of the protein pocket. However, the active sites inferred from the proteins of SARS coronavirus are not compatible with the docking site of COVID-19, which may give rise to concern in the efficacy of drugs.

scholarly journals Evaluation of COVID-19 protease and HIV inhibitors interactions

2021 ◽  
Vol 72 (1) ◽  
pp. 1-8
Author(s):  
Linh Tran ◽  
Dao Ngoc Hien Tam ◽  
Heba Elhadad ◽  
Nguyen Minh Hien ◽  
Nguyen Tien Huy
Keyword(s):  
Active Sites ◽  
Hiv Protease ◽  
Hiv Protease Inhibitors ◽  
The Novel ◽  
Autodock Vina ◽  
Novel Coronavirus ◽  
Hiv Drugs ◽  
Anti Hiv ◽  
Protein Pocket

Abstract The epidemic of the novel coronavirus disease (COVID-19) that started in 2019 has evoked an urgent demand for finding new potential therapeutic agents. In this study, we performed a molecular docking of anti-HIV drugs to refine HIV protease inhibitors and nucleotide analogues to target COVID-19. The evaluation was based on docking scores calculated by AutoDock Vina and top binding poses were analyzed. Our results suggested that lopinavir, darunavir, atazanavir, remdesivir, and tipranavir have the best binding affinity for the 3-chymotrypsin-like protease of COVID-19. The comparison of the binding sites of three drugs, namely, darunavir, atazanavir and remdesivir, showed an overlap region of the protein pocket. Our study showed a strong affinity between lopinavir, darunavir, atazanavir, tipranavir and COVID-19 protease. However, their efficacy should be confirmed by in vitro studies since there are concerns related to interference with their active sites.

scholarly journals Potential Therapeutic Agents for COVID-19 Based on the Analysis of Protease and RNA Polymerase Docking

2020 ◽  
Author(s):  
Yu-Chuan Chang ◽  
Yi-An Tung ◽  
Ko-Han Lee ◽  
Ting-Fu Chen ◽  
Yu-Chun Hsiao ◽  
...  
Keyword(s):  
Active Sites ◽  
Active Form ◽  
Therapeutic Agents ◽  
Hiv Protease ◽  
Nucleoside Triphosphate ◽  
Binding Motif ◽  
Docking Site ◽  
Binding Motifs ◽  
Functional Regions ◽  
Overlapping Region

The outbreak of novel coronavirus (COVID-19) infections in 2019 is in dire need of finding potential therapeutic agents. In this study, we used molecular docking to repurpose HIV protease inhibitors and nucleoside analogues for COVID-19, with evaluations based on docking scores calculated by AutoDock Vina and RosettaCommons. Our results suggest that Indinavir and Remdesivir possess the best docking scores, and comparison of the docking sites of the two drugs reveal a near perfect dock in the overlapping region of the protein pockets. After further investigation of the functional regions inferred from the proteins of SARS coronavirus, we discovered that Indinavir does not dock on any active sites of the protease, which may give rise to concern in regards to the efficacy of Indinavir. On the other hand, the docking site of Remdesivir is not compatible with any known functional regions, including template binding motifs, polymerization motifs and nucleoside triphosphate (NTP) binding motifs. However, when we tested the active form (CHEMBL2016761) of Remdesivir, the docking site revealed a perfect dock in the overlapping region of the NTP binding motif. This result suggests that Remdesivir could be a potential therapeutic agent. Clinical trials still must be done in order to confirm the curative effect of these drugs.

scholarly journals Potential therapeutic target identification in the novel 2019 coronavirus: insight from homology modeling and blind docking study

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Olanrewaju Ayodeji Durojaye ◽  
Talifhani Mushiana ◽  
Henrietta Onyinye Uzoeto ◽  
Samuel Cosmas ◽  
Victor Malachy Udowo ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Target Identification ◽  
Rna Virus ◽  
3D Structure ◽  
Docking Study ◽  
Therapeutic Agents ◽  
Proteolytic Processing ◽  
Hiv Protease ◽  
Hiv Protease Inhibitors ◽  
Novel Coronavirus

Abstract Background The 2019-nCoV which is regarded as a novel coronavirus is a positive-sense single-stranded RNA virus. It is infectious to humans and is the cause of the ongoing coronavirus outbreak which has elicited an emergency in public health and a call for immediate international concern has been linked to it. The coronavirus main proteinase which is also known as the 3C-like protease (3CLpro) is a very important protein in all coronaviruses for the role it plays in the replication of the virus and the proteolytic processing of the viral polyproteins. The resultant cytotoxic effect which is a product of consistent viral replication and proteolytic processing of polyproteins can be greatly reduced through the inhibition of the viral main proteinase activities. This makes the 3C-like protease of the coronavirus a potential and promising target for therapeutic agents against the viral infection. Results This study describes the detailed computational process by which the 2019-nCoV main proteinase coding sequence was mapped out from the viral full genome, translated and the resultant amino acid sequence used in modeling the protein 3D structure. Comparative physiochemical studies were carried out on the resultant target protein and its template while selected HIV protease inhibitors were docked against the protein binding sites which contained no co-crystallized ligand. Conclusion In line with results from this study which has shown great consistency with other scientific findings on coronaviruses, we recommend the administration of the selected HIV protease inhibitors as first-line therapeutic agents for the treatment of the current coronavirus epidemic.

scholarly journals Molecular Docking Study of the Potential Relevance of the Natural Compounds Isoflavone and Myricetin to COVID-19

2021 ◽  
Vol 25 (3) ◽  
pp. 271-282
Author(s):  
Didik Priyandoko ◽  
◽  
Wahyu Widowati ◽  
Mawar Subangkit ◽  
Diana Jasaputra ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Severe Acute Respiratory Syndrome ◽  
Active Sites ◽  
Docking Study ◽  
Binding Mode ◽  
Molecular Docking Study ◽  
Wuhan City ◽  
The World ◽  
Novel Coronavirus ◽  
Proteins Interactions

The 2019 novel coronavirus (2019-nCoV) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly from its origin in Wuhan City, Hubei Province, China, to the rest of the world. The efficacy of herbal treatment in the control of contagious disease was demonstrated during the 2003 outbreak of severe acute respiratory syndrome (SARS). Natural compound used for this study were isoflavone and myricetin. Molecular docking was performed to analyze binding mode of the compounds towards 12 proteins related to COVID-19. The prediction shows that isoflavone and myricetin have moderate probability of antiviral activity. All of the docked compounds occupied the active sites of the proteins related to COVID-19. Based on QSAR and molecular docking, interactions were predicted with 10 out of 12 potential COVID-19 proteins for myricetin and with 9 out of 12 proteins interactions for isoflavone. A potential disease alleviating action is suggested for isoflavone and myricetin in the context of COVID-19 infection.

scholarly journals Molecular Docking Studies and Comparative Binding Mode Analysis of FDA Approved HIV Protease Inhibitors

2014 ◽  
Vol 26 (18) ◽  
pp. 6227-6232 ◽  
Author(s):  
Pran Kishore Deb ◽  
Ahmad Junaid ◽  
Dina El-Rabie ◽  
Tan Yee Hon ◽  
Elham Mohammadi Nasr ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Protease Inhibitors ◽  
Binding Mode ◽  
Docking Studies ◽  
Hiv Protease ◽  
Mode Analysis ◽  
Hiv Protease Inhibitors ◽  
Molecular Docking Studies ◽  
Comparative Binding

scholarly journals Structure based drug discovery by virtual screening of 3699 compounds against the crystal structures of six key SARS-CoV-2 proteins

2020 ◽  
Author(s):  
Shoab Saadat ◽  
Salman Mansoor ◽  
Naveen Naqvi ◽  
Ammad Fahim ◽  
Zaira Rehman ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Crystal Structures ◽  
Active Sites ◽  
Data Bank ◽  
Spike Protein ◽  
Binding Affinities ◽  
Methyl Transferase ◽  
Main Protease ◽  
Major Outbreak ◽  
Novel Coronavirus

Abstract BackgroundThe current Novel Coronavirus (SARS-CoV-2) pandemic is the third major outbreak of the 21st century which emerged in December 2019 from Wuhan, China. At present there are no known treatments or vaccines to cure or prevent the illness.ObjectiveThe objective of this study was to explore a list of potential drugs (herbal and antivirals) for their role in inhibiting activity and or replication of SARS-CoV-2 by using molecular docking onto the crystal structures of key viral proteins.MethodologyIn this study, we used molecular docking to estimate the binding affinities of 3699 drugs on the potential active sites of the 6 main SARS-CoV-2 proteins (Papain like protease, Main protease, ADP Ribose phosphatase, Spike protein, NSP-9 and NSP-10 to 16 complex). While other studies have mostly been performed on the homology models, we obtained the most recently submitted crystal structures of all 6 proteins from the protein data bank for this analysis.ResultsOur results showed the top ligands as Theasinensin A, Epigallocatechin, Theaflavin, Theasinensin A, Epigallocatechin and Favipiravir showing the highest binding affinities against papain-like protease, ADP ribose phosphatase, main protease, spike protein, RNA replicase (NSP-9) and methyl-transferase (NSP-16) respectively.ConclusionWe show that the compounds from our list with the greatest inhibitory potential against SARS-CoV-2 activity or replication include Theasinensin A, Epigallocatechin-3-gallate, Theaflavin, Favipiravir, Curucumin, Quercetin, Mitoxantrone, Amentoflavone, Colistin, Cimicifugic acid, Theaflavin, Silymarin and Chebulagic. We recommend further wet-lab and clinical testing of these compounds to further explore their role against SARS-CoV-2.

3D-QSAR and molecular docking studies on HIV protease inhibitors

2017 ◽  
Vol 1129 ◽  
pp. 17-22 ◽  
Author(s):  
Jianbo Tong ◽  
Yingji Wu ◽  
Min Bai ◽  
Pei Zhan
Keyword(s):  
Molecular Docking ◽  
Protease Inhibitors ◽  
3D Qsar ◽  
Docking Studies ◽  
Hiv Protease ◽  
Hiv Protease Inhibitors ◽  
Molecular Docking Studies

Dose COVID-19 Uncovered a New Feature of Metronidazole Drug?

2020 ◽  
Author(s):  
Mohammad Seyedhamzeh ◽  
Bahareh Farasati Far ◽  
Mehdi Shafiee Ardestani ◽  
Shahrzad Javanshir ◽  
Fatemeh Aliabadi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Drug Discovery ◽  
Virtual Screening ◽  
Active Sites ◽  
Initial Plasma ◽  
New Feature ◽  
Metronidazole Benzoate ◽  
Global Health Problem ◽  
A Current ◽  
Pro Inflammatory Cytokines

Studies of coronavirus disease 2019 (COVID-19) as a current global health problem shown the initial plasma levels of most pro-inflammatory cytokines increased during the infection, which leads to patient countless complications. Previous studies also demonstrated that the metronidazole (MTZ) administration reduced related cytokines and improved treatment in patients. However, the effect of this drug on cytokines has not been determined. In the present study, the interaction of MTZ with cytokines was investigated using molecular docking as one of the principal methods in drug discovery and design. According to the obtained results, the IL12-metronidazole complex is more stable than other cytokines, and an increase in the surface and volume leads to prevent to bind to receptors. Moreover, ligand-based virtual screening of several libraries showed metronidazole phosphate, metronidazole benzoate, 1-[1-(2-Hydroxyethyl)-5- nitroimidazol-2-yl]-N-methylmethanimine oxide, acyclovir, and tetrahydrobiopterin (THB or BH4) like MTZ by changing the surface and volume prevents binding IL-12 to the receptor. Finally, the inhibition of the active sites of IL-12 occurred by modifying the position of the methyl and hydroxyl functional groups in MTZ. <br>

Dibenzochrysene Enables Tightly Controlled Docking and Stabilizes Photoexcited States in Dual-Pore Covalent Organic Frameworks

2019 ◽  
Author(s):  
Torben Sick ◽  
Niklas Keller ◽  
Nicolai Bach ◽  
Andreas Koszalkowski ◽  
Julian Rotter ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Photophysical Properties ◽  
Visible Spectrum ◽  
Large Family ◽  
Building Blocks ◽  
Band Gaps ◽  
Docking Site ◽  
Covalent Organic Frameworks ◽  
Connected Node ◽  
Optoelectronic Applications

Covalent organic frameworks (COFs), consisting of covalently connected organic building units, combine attractive features such as crystallinity, open porosity and widely tunable physical properties. For optoelectronic applications, the incorporation of heteroatoms into a 2D COF has the potential to yield desired photophysical properties such as lower band gaps, but can also cause lateral offsets of adjacent layers. Here, we introduce dibenzo[g,p]chrysene (DBC) as a novel building block for the synthesis of highly crystalline and porous 2D dual-pore COFs showing interesting properties for optoelectronic applications. The newly synthesized terephthalaldehyde (TA), biphenyl (Biph), and thienothiophene (TT) DBC-COFs combine conjugation in the a,b-plane with a tight packing of adjacent layers guided through the molecular DBC node serving a specific docking site for successive layers. The resulting DBC-COFs exhibit a hexagonal dual-pore kagome geometry, which is comparable to COFs containing another molecular docking site, namely 4,4′,4″,4‴-(ethylene-1,1,2,2-tetrayl)-tetraaniline (ETTA). In this context, the respective interlayer distances decrease from about 4.60 Å in ETTA-COFs to about 3.6 Å in DBC-COFs, leading to well-defined hexagonally faceted single crystals sized about 50-100 nm. The TT DBC-COFs feature broad light absorption covering large parts of the visible spectrum, while Biph DBC-COF shows extraordinary excited state lifetimes exceeding 10 ns. In combination with the large number of recently developed linear conjugated building blocks, the new DBC tetra-connected node is expected to enable the synthesis of a large family of strongly p-stacked, highly ordered 2D COFs with promising optoelectronic properties.

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