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 ◽  

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.

Author(s):  
Krzysztof Marciniec ◽  
Artur Beberok ◽  
Stanisław Boryczka ◽  
Dorota Wrześniok

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.


Author(s):  
Yustinus Maladan ◽  
Hana Krismawati ◽  
Tri Wahyuni ◽  
Hotma Martogi Lorensi Hutapea ◽  
Muhammad Fajri Rokhmad ◽  
...  

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.


2021 ◽  
Vol 12 (7) ◽  
pp. 14-21
Author(s):  
Selvarasuvasuki Manikandan ◽  
Sabeerali Ansarali ◽  
Manikandan Priyadharshini ◽  
Ganapathy Murugan Alagu Lakshmanan

Aim: Plectranthus (Linn) is a typical genus of the Indian flora. It had been used in the folk medicines for its several medicinal properties. In this study, there are twenty-five major biological compounds were selected from Plectranthus forskohlii, Plectranthus coleoides, Plectranthus rotundifolius and Plectranthus vettiveroides for molecular docking analysis and find out the active compounds against Diabetic, Cancer and Tuberculosis diseases. Materials and methods: Biological compounds of Plectranthus Species were identifying and investigated by GC-MS and the biological activities of these compounds were studied with virtual screening, ADMET analysis, Protein ligand interaction through molecular docking analysis. Results: Twenty-five major biological compounds were selected for virtual screening analysis to find out the drug likeness activity. Out of these twenty-five compounds nine compounds are drug likeness in nature. Based on the ADMET analysis, Thymol beta D-Glucoside showed the low toxicity level and it represent Lipinski rule of five. The molecular docking results of Thymol beta D-Glucoside interact with different target proteins used in the study showed the maximum docking energy was obtained against tuberculosis protein -10.1846kcal/mol followed by diabetic protein -10.8736kcal/mol and cancer protein -11.4109kcal/mol. Conclusion: Plectranthus amboinicus leaves showed significant anti-diabetic, anti-cancer, anti-tuberculosis activity when compared to other studied species such as Plectranthus forskohlii, Plectranthus coleoides, Plectranthus rotundifolius and Plectranthus vettiveroides.


2021 ◽  
Vol 17 (3) ◽  
pp. 369-376
Author(s):  
Praveen Kumar Kumar ◽  
◽  
Shanmughavel Piramanayagam ◽  

Antimicrobial peptides (AMPs) play a prominent role in drug discovery due to the rapid increase in drug resistant infections. Hence, we report the molecular docking analysis of antimicrobial peptides MREEKKERKRD and MVQGAKRGGRLHRV with the target protein CXCL1 in the context of colorectal cancer for further consideration in drug discovery.


Author(s):  
Nourhan M. Abd El-Aziz ◽  
Mohamed G. Shehata ◽  
Olfat M. Eldin Awad ◽  
Sobhy A. El-Sohaimy

Abstract Till now there is no approved treatment for COVID-19. Phenolic compounds are known to have antiviral activity against many viruses such as HCV and HIV, through their phenol rings interaction with viral proteins and/or RNA, or via its regulating MAP kinase signaling in host cell defense. The present study aimed to assess polyphenolic compounds (gallic acid, quercetin, caffeine, resveratrol, naringenin, benzoic acid, oleuropein and ellagic acid) as COVID-19 RNA-dependent RNA polymerase (PDB ID 6M71) inhibitors, using a molecular docking. Molecular docking of these polyphenols were performed using Autodock 4.0 and Chimera 1.8.1 programs. Drug likeness and polyphenols pharmacokinetic properties were calculated using SWISSADME prediction website (http://www.swissadme.ch/). Remdesivir and ribavirin were used as standard antiviral drugs for comparison. Docking analysis results, ranked by binding energy value (ΔG) of several tested ligands toward COVID-19 polymerase were; remdesivir > gallic acid > quercetin > caffeine > ribavirin > resveratrol > naringenin > benzoic acid > oleuropein > ellagic acid. The binding energies were -8.51, - 7.55, - 7.17, -6.10, - 6.01, - 5.79, - 5.69, - 5.54, - 4.94 and -4.59 kcal/mol, respectively. All tested polyphenols performed hydrogen bonds with one or two of the nucleotide triphosphate entry channel (NTP) amino acids in COVID-19 polymerase (ARG 555, ARG 555, LYS 545), except caffeine and oleuropein. Binding of polyphenols to NTP of COVID-19 polymerase may influence in the entry of the substrate and divalent cations into the central active site cavity, inhibiting the enzyme activity. It appears promising that, gallic acid and quercetin exhibited high binding affinity than ribavirin toward COVID-19 polymerase and expressed good drug likeness and pharmacokinetic properties. Therefore, gallic acid and quercetin may represent a potential treatment option for COVID-19. Further researches are urgently required to investigate the potential uses of these polyphenols in COVID-19 treatment. Additionally, resveratrol, naringenin, benzoic and ellagic acid seem to have the best potential to act as COVID-19 polymerase inhibitors.


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