Exploring the antihyperglycemic potential of tetrapeptides devised from AdMc1 <i>via</i> different receptor proteins inhibition using in silico approaches

Mustafa, Ghulam; Mahrosh, Hafiza Salaha; Zafar, Muddassar; Attique, Syed Awais; Arif, Rawaba

doi:10.1177/03946320221103120

Cited by 6 publications

(4 citation statements)

References 40 publications

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“…All selected top ten tetrapeptides fully accomplished the drug-like criteria and violated one rule ( Table 2 ). A compound could be considered a potential drug candidate, if it violates no or one rule out of five [ 23 ]. To further assess the pharmacological potential of these ten tetrapeptides, the admetSAR tool was used to predict the ADMET based attributes of these peptides from a medical perspective.…”

Section: Resultsmentioning

confidence: 99%

Identification of Plant Peptides as Novel Inhibitors of Orthohepevirus A (HEV) Capsid Protein by Virtual Screening

et al. 2023

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Hepatitis E virus (HEV) is the notable causative agent of acute and chronic hepatic, renal, pancreatic, neurological, and hematopoietic blood cell infections with high risk in immunocompromised patients. Hepatic failure is mostly documented among adults, pregnant women, and patients with preexisting liver disease. HEV is a positive sense RNA virus of 7.2 kb genome size with typically three open reading frames (ORFs) which play essential roles in viral replication, genome assembly, and transcription. The mutational substitution in the viral RNA genome makes more it difficult to understand the actual relationship in the host–virus association. ORFs of HEV encode different structural and non-structural proteins and one of them is the capsid protein which is coded by ORF2. The capsid protein mediates the encapsulation of the viral genome as well as being involved in virion assembly. In the current study, the ligand-based docking approach was employed to inhibit the active amino acids of the viral capsid protein. Depending upon S-score, ADMET profiling, and drug scanning, the top ten tetrapeptides were selected as potential drug candidates with no toxicity counter to HEV receptor protein. The S-score or docking score is a mathematical function which predicts the binding affinities of docked complexes. The binding affinity of the predicted drug–target complexes helps in the selectivity of the desired compound as a potential drug. The best two selected peptides (i.e., TDGH with S-score of −8.5 and EGDE with S-score of −8.0) interacted with the active site amino acids of the capsid protein (i.e., Arg399, Gln420, and Asp444). The molecular dynamics simulations of RMSD trajectories of TDGH–capsid protein and EDGE–capsid protein have revealed that both docked complexes were structurally stable. The study revealed that these tetrapeptides would serve as strong potential inhibitors and a starting point for the development of new drug molecules against the HEV capsid protein. In future, in vivo studies are needed to explore selected peptides as potential drug candidates.

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Section: Resultsmentioning

confidence: 99%

Identification of Plant Peptides as Novel Inhibitors of Orthohepevirus A (HEV) Capsid Protein by Virtual Screening

et al. 2023

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“…The ADME properties of molecules depend upon Lipinski's rule of five (Ro5) which is defined as: the molecular mass of a compound should not be greater than 500 g/mol; the number of hydrogen bond acceptor (HBA), and number of hydrogen bond donor (HBD) should not be greater than 10 and 5, respectively, and lipophilicity (Log P ) should be less than 5. Less than two violations of these rules are acceptable for good drug properties [ 23 , 24 ]. The SwissADME database was used to predict the ADME properties and other drug-likeness properties of small molecules.…”

Section: Methodsmentioning

confidence: 99%

In Silico Method for the Screening of Phytochemicals against Methicillin‐Resistant Staphylococcus Aureus

Tabassum

Kousar

Mustafa

et al. 2023

BioMed Research International

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Methicillin-resistant Staphylococcus aureus (MRSA) has evolved resistance even against the last resort β-lactam antibiotics. This is because of the acquisition of an additional penicillin-binding protein 2a (PBP2a) which is a resistance determinant in MRSA. Currently, available PBP2a inhibitors are ineffective against life-threatening and fatal infections caused by microorganisms. Therefore, there is an urgent need to screen natural compounds that could overpass the resistance issue alone or in combination with antibacterial drugs. We studied the interactions of different phytochemicals with PBP2a so that crosslinking of peptidoglycans could be inhibited. In structure-based drug designing, in silico approach plays a key role in determining phytochemical interactions with PBP2a. In this study, a total of 284 antimicrobial phytochemicals were screened using the molecular docking approach. The binding affinity of methicillin, -11.241 kcal/mol, was used as the threshold value. The phytochemicals having binding affinities with PBP2a stronger than methicillin were identified, and the drug-likeness properties and toxicities of the screened phytochemicals were calculated. Out of the multiple phytochemicals screened, nine were found as good inhibitors to be PBP2a, among which cyanidin, tetrandrine, cyclomorusin, lipomycin, and morusin showed strong binding potential with the receptor protein. These best-selected phytochemicals were also docked to the allosteric site of PBP2a, and most of the compounds revealed strong interactions with the allosteric site. These compounds were safe to be used as drugs because they did not show any toxicity and had good bioactivity scores. Cyanidin had the highest binding affinity (S-score of -16.061 kcal/mol) with PBP2a and with high gastrointestinal (GI) absorption. Our findings suggest that cyanidin can be used as a drug against MRSA infection either in purified form or that its structure can lead to the development of more potent anti-MRSA medicines. However, experimental studies are required to evaluate the inhibitory potential of these phytochemicals against MRSA.

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“…The compound liquoric acid violated only one rule, while the other compounds (i.e., madecassic acid, obamegine, botulin, lupeol, and berbamine) violated more than one rule of the Ro5 (Table 2). If a compound violates no rules or one out of the five, it could be considered as a potential drug candidate [13]. The admetSAR tool was also employed for further assessing the pharmacological potential of the best-selected phytochemicals through ADMET-based attributes from a medical perspective.…”

Section: Druggability Analysesmentioning

confidence: 99%

Molecular Docking and Simulation-Binding Analysis of Plant Phytochemicals with the Hepatocellular Carcinoma Targets Epidermal Growth Factor Receptor and Caspase-9

et al. 2023

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Among primary liver cancers, hepatocellular carcinoma (HCC) is one of the most common forms and it has been categorized as the joint-fourth largest reason of cancer-related deaths globally. Different factors such as alcohol abuse, hepatitis B and C, viral infections, and fatty liver diseases are mainly related to the pathogenesis of HCC. In the current study, 1000 total various plant phytochemicals were docked to proteins involved in HCC. The compounds were docked to the active site amino acids of epidermal growth factor receptor and caspase-9 as receptor proteins in order to explore their inhibiting potential. The top five compounds against each receptor protein were explored as potential drug candidates on the basis of their binding affinity and root-mean square deviation values. The top two compounds against each protein were found to be liquoric acid (S-score −9.8 kcal/mol) and madecassic acid (S-score −9.3 kcal/mol) against EGFR, and limonin (S-score −10.5 kcal/mol) and obamegine (S-score −9.3 kcal/mol) against the caspase-9 protein. The selected phytochemicals were further assessed through drug scanning using Lipinski’s rule of five to explore their molecular properties and druggability. According to the ADMET analysis, the selected phytochemicals were found to be non-toxic and non-carcinogenic. Finally, the molecular dynamics simulation study revealed that liquoric acid and limonin were stabilized within the binding pockets of EGFR and capase-9, respectively, and stayed firmly bound throughout the simulation. In light of the current findings, the phytochemicals reported in this study, especially liquoric acid and limonin, could be used as potential drugs for the treatment of HCC in the future.

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Exploring the antihyperglycemic potential of tetrapeptides devised from AdMc1 via different receptor proteins inhibition using in silico approaches

Cited by 6 publications

References 40 publications

Identification of Plant Peptides as Novel Inhibitors of Orthohepevirus A (HEV) Capsid Protein by Virtual Screening

Identification of Plant Peptides as Novel Inhibitors of Orthohepevirus A (HEV) Capsid Protein by Virtual Screening

In Silico Method for the Screening of Phytochemicals against Methicillin‐Resistant Staphylococcus Aureus

Molecular Docking and Simulation-Binding Analysis of Plant Phytochemicals with the Hepatocellular Carcinoma Targets Epidermal Growth Factor Receptor and Caspase-9

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