scholarly journals The application of in silico experimental model in the assessment of ciprofloxacin and levofloxacin interaction with main SARS-CoV-2 targets: S-, E- and TMPRSS2 proteins, RNA-dependent RNA polymerase and papain-like protease (PLpro)—preliminary molecular docking analysis

2021 ◽  
Author(s):  
Krzysztof Marciniec ◽  
Artur Beberok ◽  
Stanisław Boryczka ◽  
Dorota Wrześniok
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Rna Polymerase ◽  
Stable Complex ◽  
E Proteins ◽  
Rna Dependent Rna Polymerase ◽  
Docking Analysis ◽  
Molecular Studies ◽  
Molecular Docking Analysis ◽  
Positive Controls

Abstract Background The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified at the end of 2019. Despite growing understanding of SARS-CoV-2 in virology as well as many molecular studies, except remdesivir, no specific anti-SARS-CoV-2 drug has been officially approved. Methods In the present study molecular docking technique was applied to test binding affinity of ciprofloxacin and levofloxacin—two commercially available fluoroquinolones, to SARS-CoV-2 S-, E- and TMPRSS2 proteins, RNA-dependent RNA polymerase and papain-like protease (PLPRO). Chloroquine and dexamethasone were used as reference positive controls. Results When analyzing the molecular docking data it was noticed that ciprofloxacin and levofloxacin possess lower binding energy with S protein as compared to the references. In the case of TMPRSS2 protein and PLPRO protease the best docked ligand was levofloxacin and in the case of E proteins and RNA-dependent RNA polymerase the best docked ligands were levofloxacin and dexamethasone. Moreover, a molecular dynamics study also reveals that ciprofloxacin and levofloxacin form a stable complex with E- and TMPRSS2 proteins, RNA polymerase and papain-like protease (PLPRO). Conclusions The revealed data indicate that ciprofloxacin and levofloxacin could interact and potentially inhibit crucial SARS-CoV-2 proteins.

scholarly journals Molecular docking analysis of SARS-CoV-2 linked RNA dependent RNA polymerase (RdRp) with compounds from Plectranthus amboinicus

2021 ◽  
Vol 17 (1) ◽  
pp. 167-170
Author(s):  
Jayaraman Selvaraj ◽  
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
Rosmarinic Acid ◽  
Target Protein ◽  
Coumaric Acid ◽  
Rna Dependent Rna Polymerase ◽  
Docking Analysis ◽  
Salvianolic Acid ◽  
Plectranthus Amboinicus ◽  
Molecular Docking Analysis

It is of interest to document the moelcular docking analysis of SARS-CoV-2 linked RNA dependent RNA polymerase (RdRp) with compounds from Plectranthus amboinicus. Hence, we report the binding features of rutin, Luteolin, Salvianolic acid A, Rosmarinic acid and p-Coumaric acid with the target protein SARS-CoV-2 linked RNA dependent RNA polymerase (RdRp) for further consideration.

scholarly journals Molecular Docking Analysis of the T450A Mutation of the Gene rpoB Mycobacterium leprae from Leprosy Patients in Papua, West Papua and North Maluku, Indonesia

2021 ◽  
pp. 3578-3584
Author(s):  
Yustinus Maladan ◽  
Hana Krismawati ◽  
Tri Wahyuni ◽  
Hotma Martogi Lorensi Hutapea ◽  
Muhammad Fajri Rokhmad ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
Binding Affinity ◽  
Rpob Gene ◽  
Ramachandran Plot ◽  
Docking Analysis ◽  
West Papua ◽  
Leprosy Patients ◽  
Subunit B ◽  
Molecular Docking Analysis

Leprosy persists to be a health problem in Indonesia, especially in the provinces of North Maluku, West Papua and Papua. Early diagnosis and complete treatment with multidrug therapy (MDT) remain the key strategy for reducing the disease burden. One of the major components of MDT is rifampicin which in certain cases in several countries, M. leprae resistance to this drug issue has been reported albeit only a few. This research aimed to detect and analyze polymorphism in M. leprae rpoB gene that was isolated from leprosy patients in three provinces: North Maluku Province, West Papua Province and Papua Province, Indonesia. The identification of mutations in the M. leprae rpoB gene was carried out by aligning the results of DNA sequencing with the reference strain. The 3D structure of rpoB was derived using the Swiss Model. The T450A, S456L, and H451Y variants of RNA Polymerase B subunits were constructed using FoldX based on the wild-type structure. The structures were repaired, and protein stability was evaluated using foldX under the Yasara viewer. The QC of the rpoB M. leprae homology models was conducted with Ramachandran Plot modeling using PROCHECK. The difference in binding affinity between native protein and T450A, S456L, and H45I variants were analyzed using molecular docking. rpoB gene of M. leprae contains a mutation found in nucleotide of 1348 bp. The mutation triggered the conversion of the amino acid Threonine to Alanine in the amino acid to 450 rpoB subunit B. The structure of 3D RNA Polymerase Subunit B was constructed using rpoB Mycobacterium tuberculosis with PDB code 5UH5 as template. According to Ramachandran Plot, the percentage of residues in the most favored regions are 91.9%, and there was no significant number of residues in the disallowed regions. The results of molecular docking showed that the T450A variant had the same binding affinity with the native protein which was -8.9 kcal. Binding affinity on the S456L and H451Y variants increased by -7.3 kcal and -8.2 kcal, respectively. According to Molecular Docking analysis, T450A variant did not affect the energy binding between RNA polymerase and rifampicin.

Molecular docking and molecular dynamics studies on β-lactamases and penicillin binding proteins

2014 ◽  
Vol 10 (4) ◽  
pp. 891-900 ◽  
Author(s):  
K. M. Kumar ◽  
Anand Anbarasu ◽  
Sudha Ramaiah
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
High Stability ◽  
Binding Proteins ◽  
Simulation Studies ◽  
Docking Analysis ◽  
Penicillin Binding Proteins ◽  
The Stability ◽  
Molecular Docking Analysis

Molecular docking analysis of β-lactam antibiotics was performed with PBP2a, PBP2b, PBP2x and SHV-1 proteins, and the best interaction is observed between Ceftobiprole and the PBP2x complex; furthermore the stability of the complex is confirmed using simulation studies; our results show that the Ceftobiprole–PBP2x complex shows high stability as evident by RMSD,Rgand H-bonds.

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>

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.

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