scholarly journals Identification of Potent COVID-19 Main Protease (Mpro) Inhibitors from Natural Polyphenols: An in Silico Strategy Unveils a Hope against CORONA

2020 ◽  
Author(s):  
Sevki Adem ◽  
Volkan Eyupoglu ◽  
Iqra Sarfraz ◽  
Azhar Rasul ◽  
Muhammad Ali
Keyword(s):  
Molecular Docking ◽  
Drug Target ◽  
Docking Study ◽  
Binding Energies ◽  
Therapeutic Drug ◽  
Molecular Docking Study ◽  
Molegro Virtual Docker ◽  
Main Protease ◽  
Chinese Researcher ◽  
Native Ligand

COVID-19, a rapidly spreading new strain of coronavirus, has affected more than 150 countries and received worldwide attention. The lack of efficacious drugs or vaccines against SARS-CoV-2 has further worsened the situation. Thus, there is an urgent need to boost up research for the development of effective therapeutics and affordable diagnostic against COVID-19. The crystallized form of SARS-CoV-2 main protease (Mpro) was demonstrated by a Chinese researcher Liu et al. (2020) which is a novel therapeutic drug target. This study was conducted to evaluate the efficacy of medicinal plant-based bioactive compounds against COVID-19 Mpro by molecular docking study. Molecular docking investigations were performed by using Molegro Virtual Docker 7 to analyze the inhibition probability of these compounds against COVID-19. COVID-19 Mpro was docked with 80 flavonoid compounds and the binding energies were obtained from the docking of (PDB ID: 6LU7: Resolution 2.16 Å) with the native ligand. According to obtained results, hesperidin, rutin, diosmin, apiin, diacetylcurcumin, (E)-1-(2-Hydroxy-4-methoxyphenyl)-3-[3-[(E)-3-(2-hydroxy-4- methoxyphenyl)-3-oxoprop-1-enyl]phenyl]prop-2-en-1-one, and beta,beta'-(4-Methoxy-1,3- phenylene)bis(2'-hydroxy-4',6'-dimethoxyacrylophenone have been found as more effective on COVID-19 than nelfinavir. So, this study will pave a way for doing advanced experimental research to evaluate the real medicinal potential of these compounds to cure COVID-19.

scholarly journals Some Compounds from Neem leaves extract exhibit binding affinity as high as -14.3 kcal/mol against COVID-19 Main Protease (Mpro): A Molecular Docking Study

2020 ◽  
Author(s):  
Shanmuga Subramanian S
Keyword(s):  
Molecular Docking ◽  
Treatment Option ◽  
Vitamin B1 ◽  
Antiviral Agent ◽  
Docking Study ◽  
Binding Energies ◽  
Potential Treatment ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Neem Leaves

Abstract Currently the new Coronavirus "COVID-19", also known as SARS-CoV-2, has infected nearly 3 million patients and nearly 200,000+ people have lost their lives due to this pandemic. There is an urgent need to find an antiviral agent that may slow down the spread of the virus. The aim of this study is to assess and evaluate compounds present in leaves of Neem tree (Azadirachta Indica) as potential inhibitors for COVID-19 Main Protease (Mpro) (PDB code: 6LU7). This will be done by blind molecular docking using PyRx and Auto Vina software. The compounds Hydroxychloroquine and Remdesivir were used for comparative study. The binding energies obtained from the docking of 6LU7 with meliacinanhydride, nimocinol, isomeldenin, nimbolide, zafaral, nimbandiol, nimbin, nimbinene, desacetylnimbin were -14.3, -12.4, -12.3, -12.2, -11.9, -11.8, -11.7, -11.7, -11.4 kcal/mol respectively. Therefore Meliacinanhydride (Ki=33.36 pM) and the compounds from Neem leaves may be a potential treatment option against COVID-19. In addition to that the leaves contain others compounds like Quercetin, Zinc,Vitamin A,Vitamin B1,B2,B6, Vitamin C,Vitamin E etc., which may boost immunity also (Garba, 2019) .Further investigation is needed to evaluate the results of this study to consider Neem leaves as potential treatment option as it might inhibit the virus and boost immunity also

scholarly journals Comparative Docking Analysis of Rational Drugs Against COVID-19 Main Protease

2020 ◽  
Author(s):  
LALIT SAMANT ◽  
Vyomesh Javle
Keyword(s):  
Molecular Docking ◽  
Treatment Options ◽  
Docking Study ◽  
Binding Energies ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Discovery Studio ◽  
Main Protease ◽  
Medicinal Use ◽  
Lamarckian Genetic Algorithm

COVID-19, a new strain of coronavirus (CoV), was identified in Wuhan, China, in 2019. No specific therapies are available, and investigations regarding COVID-19 treatment are lacking. Crystallised COVID-19 main protease (Mpro), which is a potential drug target. The present study aimed to assess drugs found in literature as potential COVID-19 Mpro inhibitors, using a molecular docking study. Molecular docking was performed using Autodock 4.2, with the Lamarckian Genetic Algorithm, to analyse the probability of docking. The docking was cross-validated using Swiss Dock. COVID-19 Mpro was docked with several compounds, and docking was analysed by Biovia Discovery Studio 2020. Quinine and hydroxychloroquine were used as standards for comparison. The binding energies obtained from the docking of 6LU7, 2GTB with screened drugs viz., Quinine, Artesunate, Clotrimazol, Artemether, Quercetin, Mefloquine, ciprofloxacin, clindamycin, cipargamin, SJ-733 were in between -7.0 to -9.6 kcal/mol. On consideration of similar binding energy obtained from Autodock vina and SWISSDock and interaction residue pattern specifically (GLU 166,CYS 145, CYS44 and MET 49 residue) for SJ-733 & JPC-3210 may represent potential treatment options, and appeared to have the best potential to act as COVID-19 Mpro inhibitors. However, further research is necessary to investigate their potential medicinal use against CoV.

scholarly journals Potential Inhibitor of COVID-19 Main Protease (Mpro) From Several Medicinal Plant Compounds by Molecular Docking Study

2020 ◽  
Author(s):  
Siti Khaerunnisa ◽  
Hendra Kurniawan ◽  
Rizki Awaluddin ◽  
Suhartati Suhartati ◽  
Soetjipto Soetjipto
Keyword(s):  
Molecular Docking ◽  
Treatment Options ◽  
Docking Study ◽  
Binding Energies ◽  
Molecular Docking Study ◽  
Epicatechin Gallate ◽  
Discovery Studio ◽  
Main Protease ◽  
Lamarckian Genetic Algorithm ◽  
Autodock 4.2

COVID-19, a new strain of coronavirus (CoV), was identified in Wuhan, China, in 2019. No specific therapies are available and investigations regarding COVID-19 treatment are lacking. Liu et al. (2020) successfully crystallised the COVID-19 main protease (Mpro), which is a potential drug target. The present study aimed to assess bioactive compounds found in medicinal plants as potential COVID-19 Mpro inhibitors, using a molecular docking study. Molecular docking was performed using Autodock 4.2, with the Lamarckian Genetic Algorithm, to analyse the probability of docking. COVID-19 Mpro was docked with several compounds, and docking was analysed by Autodock 4.2, Pymol version 1.7.4.5 Edu, and Biovia Discovery Studio 4.5. Nelfinavir and lopinavir were used as standards for comparison. The binding energies obtained from the docking of 6LU7 with native ligand, nelfinavir, lopinavir, kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, epicatechin-gallate, zingerol, gingerol, and allicin were -8.37, -10.72, -9.41, -8.58, -8.47, -8.17, -7.99, -7.89, -7.83, -7.31, -7.05, -7.24, -6.67, -5.40, -5.38, and -4.03 kcal/mol, respectively. Therefore, nelfinavir and lopinavir may represent potential treatment options, and kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, and epicatechin-gallate appeared to have the best potential to act as COVID-19 Mpro inhibitors. However, further research is necessary to investigate their potential medicinal use.

scholarly journals Azole-acridine hybrids as potential enzymatic inhibitors of coronavirus-2 main protease and RNA polymerase by molecular modeling strategy

2020 ◽  
Author(s):  
Charles K. Rono ◽  
Banothile C.E. Makhubela
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
Docking Study ◽  
Living Cells ◽  
Binding Energies ◽  
Binding Affinities ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Current Outbreak ◽  
Modeling Strategy

Abstract SARS-CoV-2 has been identified as the cause of the current outbreak of coronavirus disease (COVID-19). As part of the efforts to develop potential drugs with promise for clinical use, a molecular docking study on azole (triazole and pyrazole) based molecules on the main protease Mpro and RNA polymerase as possible inhibitors that could be elected for further experimental bioassays. Autodock has been employed to identify azole derivatives 1-6 preferred conformations in the active site of the enzyme and to estimate their binding affinities to the protease and RNA polymerase targets. From the molecular docking strategy, these new azole compounds though nonpeptides in nature display possible inhibition of Mpro activity with comparable affinities (-4.7 kcal/mol to -6.5 kcal/mol) to the recently reported peptide-like inhibitors such as α-ketoamide inhibitor 13b (-5.0 k/cal/mol). They also exhibit improved binding affinities to RNA polymerase (-6.3 to -7.1 kcal/mol) comparable to remdesivir (-6.6 kcal/mol). Based on the observed binding energies, these compounds may possess anti-coronavirus bioactivity through inhibition of the virus main protease as well as RNA polymerase activities in living cells.

scholarly journals Identification of potent COVID-19 main protease (MPRO) inhibitors from flavonoids

2020 ◽  
Author(s):  
Anita Chauhan ◽  
Seema Kalra
Keyword(s):  
Drug Target ◽  
Binding Capacity ◽  
Treatment Options ◽  
Docking Study ◽  
Binding Energies ◽  
Targeted Therapeutics ◽  
Molecular Docking Study ◽  
Drug Candidates ◽  
Main Protease ◽  
Target Molecules

Abstract COVID-19 epidemic that commenced in Wuhan in December 2019 has spread worldwide within a few months. Currently, there are no targeted therapeutics and effective treatment options remain very limited. Mpro is a key CoV enzyme, which plays a pivotal role in viral replication and transcription, making it an attractive drug target for this virus. This study was conducted to evaluate the efficacy of flavonoids as drug target molecules against COVID-19 Mpro by molecular docking study. COVID-19 Mpro was docked with 14 flavonoid compounds as well as 4 already existing drugs and the binding energies were determined.Based on the results,we have identified two potential flavonoids with high binding capacity and possible drug candidates. This study will pave a way for doing advanced experimental research to evaluate the real medicinal potential of these compounds to cure COVID-19.

scholarly journals Azole-acridine hybrids as potential enzymatic inhibitors of coronavirus-2 main protease and RNA polymerase by molecular modeling strategy

2020 ◽  
Author(s):  
Charles K. Rono ◽  
Banothile C.E. Makhubela
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
Docking Study ◽  
Living Cells ◽  
Binding Energies ◽  
Binding Affinities ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Current Outbreak ◽  
Modeling Strategy

Abstract SARS-CoV-2 has been identified as the cause of the current outbreak of coronavirus disease (COVID-19). As part of the efforts to develop potential drugs with promise for clinical use, a molecular docking study on azole (triazole and pyrazole) based molecules on the main protease Mpro and RNA polymerase was conducted, as possible inhibitors that could be elected for further experimental bioassays. Autodock has been employed to identify azole derivatives 1-6 preferred conformations in the active site of the enzyme and to estimate their binding affinities to the protease and RNA polymerase targets. From the molecular docking strategy, these new azole compounds though nonpeptides in nature display possible inhibition of Mpro activity with comparable affinities (-4.7 kcal/mol to -6.5 kcal/mol) to the recently reported peptide-like inhibitors such as α-ketoamide inhibitor 13b (-5.0 k/cal/mol). They also exhibit improved binding affinities to RNA polymerase (-6.3 to -7.1 kcal/mol) comparable to remdesivir (-6.6 kcal/mol). Based on the observed binding energies, these compounds may possess anti-coronavirus bioactivity through inhibition of the virus main protease as well as RNA polymerase activities in living cells.

scholarly journals Comparative Docking Analysis of Rational Drugs Against COVID-19 Main Protease

2020 ◽  
Author(s):  
LALIT SAMANT ◽  
Vyomesh Javle
Keyword(s):  
Molecular Docking ◽  
Treatment Options ◽  
Docking Study ◽  
Binding Energies ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Discovery Studio ◽  
Main Protease ◽  
Medicinal Use ◽  
Lamarckian Genetic Algorithm

COVID-19, a new strain of coronavirus (CoV), was identified in Wuhan, China, in 2019. No specific therapies are available, and investigations regarding COVID-19 treatment are lacking. Crystallised COVID-19 main protease (Mpro), which is a potential drug target. The present study aimed to assess drugs found in literature as potential COVID-19 Mpro inhibitors, using a molecular docking study. Molecular docking was performed using Autodock 4.2, with the Lamarckian Genetic Algorithm, to analyse the probability of docking. The docking was cross-validated using Swiss Dock. COVID-19 Mpro was docked with several compounds, and docking was analysed by Biovia Discovery Studio 2020. Quinine and hydroxychloroquine were used as standards for comparison. The binding energies obtained from the docking of 6LU7, 2GTB with screened drugs viz., Quinine, Artesunate, Clotrimazol, Artemether, Quercetin, Mefloquine, ciprofloxacin, clindamycin, cipargamin, SJ-733 were in between -7.0 to -9.6 kcal/mol. On consideration of similar binding energy obtained from Autodock vina and SWISSDock and interaction residue pattern specifically (GLU 166,CYS 145, CYS44 and MET 49 residue) for SJ-733 & JPC-3210 may represent potential treatment options, and appeared to have the best potential to act as COVID-19 Mpro inhibitors. However, further research is necessary to investigate their potential medicinal use against CoV.

scholarly journals Nearly 20+ compounds in Neem leaves extract exhibit high binding affinity with some of them as high as -14.3 kcal/mol against COVID-19 Main Protease (Mpro) : A Molecular Docking Study

2020 ◽  
Author(s):  
Shanmuga Subramanian
Keyword(s):  
Molecular Docking ◽  
Treatment Option ◽  
Vitamin B1 ◽  
Antiviral Agent ◽  
Preventive Treatment ◽  
Docking Study ◽  
Binding Energies ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Neem Leaves

Currently the new disease "COVID-19", caused by SARS-CoV-2, has infected nearly 3 million patients and nearly 200,000+ people have lost their lives due to this pandemic. There is an urgent need to find an antiviral agent that may slow down the spread of the virus. The aim of this study is to assess and evaluate compounds present in leaves of Neem tree (Azadirachta Indica) as potential inhibitors for COVID-19 Main Protease (Mpro) (PDB code: 6LU7). This will be done by blind molecular docking using PyRx and Auto Vina software. The compounds Hydroxychloroquine and Remdesivir were used for comparative study. The binding energies obtained from the docking of 6LU7 with Meliacinanhydride, IsoNimocinolide, Nimocino, 22, 23-dihydronimocinol, Nimonol, isomeldenin, zafaral, nimbandiol, Nimbin, Nimbanal, Nimbinene, Desacetylnimbin, Azadirachtin D, Azadirachtin B, Azadirachtin I, Azadirachtin A,2-tert-Butyl-1,3-diphenyl-4,5,6,7-tetrahydroindole, 3-Deacetylsalannin, Azadirachtin H,2′,3′-dehydrosalannol, Salannin (Azadriactin) were -14.3, -12.9, -12.3, -12.2, -12.2, -12.2, -12, -11.9, -11.8, -11.7, -11.7, -11.7, -11.4, -11.1,-10.8,-10.7,-10.6,-10.6,-10.6,-10.5,-10.2,-9.8 kcal/mol respectively. Therefore Meliacinanhydride (Ki=33.36 pM) and the compounds from Neem leaves may be a potential preventive treatment option against COVID-19. In addition to that the leaves contain others compounds like Quercetin, Zinc,Vitamin A,Vitamin B1,B2,B6, Vitamin C,Vitamin E etc., which may boost immunity also (Garba, 2019) .Further investigation is needed to evaluate the results of this study to consider Neem leaves as potential preventive treatment option as it might inhibit the virus and boost immunity also, thereby slowing the spread of COVID-19.

scholarly journals Metal-Bound Methisazone; Novel Drugs Targeting Prophylaxis and Treatment of SARS-CoV-2, a Molecular Docking Study

2021 ◽  
Vol 22 (6) ◽  
pp. 2977
Author(s):  
Ahmed Abdelaal Ahmed Mahmoud M. Alkhatip ◽  
Michail Georgakis ◽  
Lucio R. Montero Valenzuela ◽  
Mohamed Hamza ◽  
Ehab Farag ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Study ◽  
Docking Studies ◽  
Binding Energies ◽  
Spike Protein ◽  
Molecular Docking Study ◽  
In Silico Docking ◽  
Main Protease ◽  
Binding Pockets

SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at −8.3 kcal/mol, followed by Zn and Ca at −8.0 kcal/mol, and Fe and Mg at −7.9 kcal/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be singly or multiply occupied on all proteins tested. The best binding energy was with Mn–Methisazone versus spike protein, and the largest cumulative increases in binding energies were found with PlPr. We suggest that further studies are warranted to identify whether these compounds may be effective for treatment and/or prophylaxis.

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