SARS-CoV-2 main protease and papain-like protease inhibition by abietane-type diterpenes isolated from the branches of Glyptostrobus pensilis using molecular docking studies

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.

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MOLECULAR DOCKING STUDIES ON SCREENING AND ASSESSMENT OF SELECTED BIOFLAVONOIDS AS POTENTIAL INHIBITORS OF COVID-19 MAIN PROTEASE

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2020.v13i9.38485 ◽

2020 ◽

pp. 174-178

Author(s):

SHAILENDRA SANJAY SURYAWANSHI ◽

POOJA BHAVAKANA JAYANNACHE ◽

RAJKUMAR SANJAY PATIL ◽

PALLED MS ◽

ALEGAON SG

Keyword(s):

Molecular Docking ◽

Treatment Options ◽

Docking Studies ◽

Binding Energies ◽

Molecular Docking Studies ◽

Discovery Studio ◽

Main Protease ◽

Potential Inhibitors ◽

Binding Energy Calculations ◽

Native Ligand

Objectives: The objective of the study was to screen and assess the selected bioactive bioflavonoids in medicinal plants as potential coronaviruses (CoV) main protease (Mpro) inhibitors using molecular docking studies. Methods: We have investigated several bioflavonoids which include apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin. Nelfinavir and lopinavir were used as standard antiviral drugs for comparison. Mpro was docked with selected compounds using PyRx 0.8 and docking was analyzed by PyRx 0.8 and Biovia Discovery Studio 2019. Results: The binding energies obtained from the docking of 6LU7 with native ligand, nelfinavir, lopinavir, apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin were found to be −7.4, −8.3, −8.0, −7.8, −7.3, −7, −7.4, −7.6, −7.8, −6.9, and −9 kcal/mol, respectively. Conclusion: From the binding energy calculations, we can conclude that nelfinavir and lopinavir may represent potential treatment options and apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin found to possess the best inhibitors of CoV disease-19 main protease.

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Molecular Docking Studies of N-Acetyl Cysteine, Zinc Acetyl Cysteine and Niclosamide on SARS Cov 2 Protease and Its Comparison with Hydroxychloroquine

10.26434/chemrxiv.12161493.v1 ◽

2020 ◽

Author(s):

Roopa Guthappa

Keyword(s):

Molecular Docking ◽

Binding Energy ◽

Active Sites ◽

Antiviral Drug ◽

Docking Studies ◽

Binding Affinities ◽

Binding Interaction ◽

Molecular Docking Studies ◽

Main Protease ◽

Acetyl Cysteine

To Respected Sir/Madam Chemarxiv Respected Sir/Madam Sub: submission of preprint of article to Chemarxiv for online publication. I am herewith submitting the preprint of an article entitled “Molecular docking studies of N-acetyl cysteine, zinc acetyl cysteine and niclosamide on SARS Cov 2 protease and its comparison with hydroxychloroquine” for possible publication in “Chemarxiv”. In this article, we have evaluated the binding abilities of N-acetyl cysteine, zinc acetyl cysteine and niclosamide (antiviral drug) with SARS-COV-2 protease. All the four compounds investigated are effective and selectively bind to active sites of main protease. N-acetyl cysteine being a derivative of cysteine interacts with Cys-145, His-163, Gly-143 of COV-2 protease, zinc acetyl cysteine binds to Gly-143, Ser-144, Cys-145, Glu-166 of COV-2 protease and niclosamide bind to Glu-166, Cys-145, His 41 of main protease. The data has been compared with hydroxychloroquine which effectively binds to Cys-145, Glu-166, Arg-188. The binding affinities of N-acetyl cysteine, zinc-acetyl cysteine and niclosamide are -4.24, -4.29 and -7.5 kcal mol-1 while for hydroxychloroquine it is -6.66 kcal mol-1. Niclosamide with its lowest binding energy interacts with His-41 and Cys-145 which may be the first molecule to show such binding interaction. The results indicate that N-acetyl cysteine, zinc-acetyl cysteine and niclosamide can also be explored for the treatment for SARS COV-2 as an alternative for hydroxychloroquine. I hope that the manuscript will full fill the journal’s requirements and will get accepted for publication. Thanking you With regards Roopa Guthappa <a href="mailto:[email protected]">[email protected]</a>

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Binding Ability Studies of Arginine, Citrulline, N-Acetyl Citrulline and Thiocitrulline with SARS Cov-2 Main Protease Using Molecular Docking Studies

10.26434/chemrxiv.12196833.v1 ◽

2020 ◽

Author(s):

Ramesh Thimmasandra Narayan

Keyword(s):

Molecular Docking ◽

Active Sites ◽

Docking Studies ◽

The Other ◽

Binding Affinities ◽

Binding Ability ◽

Molecular Docking Studies ◽

Main Protease ◽

Structural Analogues ◽

Preferential Binding

To Editor in Chief Chemarxiv Respected Sir/Madam Subject: submission of preprint of an article to ChemRxiv on molecular docking studies of arginine and its structural analogues on COV-19 for publication. I am herewith submitting the preprint of an article entitled “Binding ability studies of arginine, citrulline, N-acetyl citrulline and thiocitrulline with SARS Cov-2 main protease using molecular docking studies.” for publication as preprint in “ChemRxiv”. In this paper the binding abilities of arginine, citrulline, N-acetyl citrulline and thiocitrulline with SARS-COV-2 protease have been examined using molecular docking studies. The ligands used for docking has moderate binding affinity to active sites of main protease in terms of values. The binding affinities of these ligands are in the range of -3.1 to -5.1 kcal mol-1. All the ligands bind selectively to Cys-145 and also to other amino acids surrounding to it in the main protease. Of which arginine forms less number of weaker bonds compared to the other ligands, it by itself is a precursor for the formation of citrulline analogues with in the cell. Major advantage of using the above ligands is that in addition to its preferential binding these molecules also have the ability to enhance the immunity of the cells by the generation of nitric oxide in presence of enzymes thereby protecting them. Our results show that N-acetyl citrulline, citrulline, thiocitrulline and arginine may be used as a supplement during the treatment of SARS-COV-2. I request your good self to kindly accept the article and get it published as pre-print in your esteemed ChemRxiv. Thanking you With regards Ramesh T N ([email protected])

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Molecular Docking Studies of N-Acetyl Cysteine, Zinc Acetyl Cysteine and Niclosamide on SARS Cov 2 Protease and Its Comparison with Hydroxychloroquine

10.26434/chemrxiv.12161493 ◽

2020 ◽

Author(s):

Roopa Guthappa

Keyword(s):

Molecular Docking ◽

Binding Energy ◽

Active Sites ◽

Antiviral Drug ◽

Docking Studies ◽

Binding Affinities ◽

Binding Interaction ◽

Molecular Docking Studies ◽

Main Protease ◽

Acetyl Cysteine

To Respected Sir/Madam Chemarxiv Respected Sir/Madam Sub: submission of preprint of article to Chemarxiv for online publication. I am herewith submitting the preprint of an article entitled “Molecular docking studies of N-acetyl cysteine, zinc acetyl cysteine and niclosamide on SARS Cov 2 protease and its comparison with hydroxychloroquine” for possible publication in “Chemarxiv”. In this article, we have evaluated the binding abilities of N-acetyl cysteine, zinc acetyl cysteine and niclosamide (antiviral drug) with SARS-COV-2 protease. All the four compounds investigated are effective and selectively bind to active sites of main protease. N-acetyl cysteine being a derivative of cysteine interacts with Cys-145, His-163, Gly-143 of COV-2 protease, zinc acetyl cysteine binds to Gly-143, Ser-144, Cys-145, Glu-166 of COV-2 protease and niclosamide bind to Glu-166, Cys-145, His 41 of main protease. The data has been compared with hydroxychloroquine which effectively binds to Cys-145, Glu-166, Arg-188. The binding affinities of N-acetyl cysteine, zinc-acetyl cysteine and niclosamide are -4.24, -4.29 and -7.5 kcal mol-1 while for hydroxychloroquine it is -6.66 kcal mol-1. Niclosamide with its lowest binding energy interacts with His-41 and Cys-145 which may be the first molecule to show such binding interaction. The results indicate that N-acetyl cysteine, zinc-acetyl cysteine and niclosamide can also be explored for the treatment for SARS COV-2 as an alternative for hydroxychloroquine. I hope that the manuscript will full fill the journal’s requirements and will get accepted for publication. Thanking you With regards Roopa Guthappa <a href="mailto:[email protected]">[email protected]</a>

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Molecular Docking Studies of Bioactive Nicotiflorin against 6W63 Novel Coronavirus 2019 (COVID-19)

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323999200820162551 ◽

2020 ◽

Vol 23 ◽

Author(s):

Raghvendra Dubey ◽

Kushagra Dubey

Keyword(s):

Molecular Docking ◽

Data Bank ◽

Docking Studies ◽

Molecular Docking Studies ◽

Molegro Virtual Docker ◽

Main Protease ◽

Docking Approach ◽

Inhibitory Potential ◽

Efficacy Parameters ◽

Novel Coronavirus

Background: COVID-19 which is known as the novel coronavirus was reported in December 2019 in Wuhan city, China and many of the patients have been contaminated by environmental contamination and transmission from one human to another. Objective: The objective of work is to establish the inhibitory potential of nicotiflorin, a Kaempferol 3-O-rutinoside flavonoid, against the deadly coronavirus (COVID-19) 6W63 (main protease 3Clpro protein) , using molecular docking approach. Method: The Molegro Virtual Docker software (MVD) with a 30 Å grid resolution was used. The structure was drawn by Chem 3D software and energy minimization was done by the MM2 force field. The protein 6W63 was downloaded from the protein data bank. Molegro modeller was used for score calculations. Result: The molecular docking studies were carried out on nicotiflorin and standard inhibitor X77, where standard inhibitor was observed in a co-crystallized state with main protease 3Clpro protein 6W63. The MolDock score, Rerank Sore and H Bond score of nicotiflorin and standard inhibitor X77 was observed as -173.058, -127.302, -21.9398 and -156.913,- 121.296,-5.7369, respectively. Conclusion: Molecular docking studies have confirmed that the affinity of flavonoid nicotiflorin with the amino acids of the viral protein 6W63 was relatively more than the standard X77. For the effective treatment of novel coronavirus COVID-19, the effectiveness of the identified flavonoid nicotiflorin can further be evaluated for safety and efficacy parameters at both preclinical and clinical stages.

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Molecular Docking Studies of Some Natural Products Against SARS-CoV-2 Main Protease: Potential Therapeutic Agents for COVID-19

Asian Journal of Organic & Medicinal Chemistry ◽

10.14233/ajomc.2020.ajomc-p288 ◽

2020 ◽

Vol 5 (3) ◽

pp. 254-264

Author(s):

Gnanavel Sadhasivam

Keyword(s):

Natural Products ◽

Molecular Docking ◽

Natural Compounds ◽

Docking Studies ◽

Severe Form ◽

Marine Sponges ◽

Health Crisis ◽

Molecular Docking Studies ◽

Main Protease ◽

Second World

The severe form of respiratory disease (COVID-19), caused by SARS-COV-2 virus, has evolved into a pandemic is the defining global health crisis of our time and greatest challenge we have faced since second World War. Hence, the current situation demands an immediate need to explore all the possible therapeutic strategies that can be control spread of the diseases. We identified potent COVID-19 Mpro inhibitors based on molecular docking studies on 24 known antiviral natural compounds, which are from medicinal plants and marine sponges. The results revealed that 15 potential COVID-19 main protease inhibitors have been identified among the 24 natural compounds of plants and marine origin. The result further revealed that the selected natural products that has lower free binding energy is Halituline (-8.41 Kcal/mol). As these active compounds were extensively validated by molecular docking, the chance that at least few of these compounds could be bioactive is excellent.

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