Biomimetic Design of Peptide Neutralizer of Ebola Virus with Molecular Simulation

Hou, Qianqian; Zhang, Lin

doi:10.1021/acs.langmuir.9b03832

Cited by 19 publications

(19 citation statements)

References 42 publications

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“…Hence, new functions of the natural histidine-rich protein related to human health care are expected to be identified by investigating their cell membrane permeation. Although the biomimetic approach has recently become popular for the creation of artificial functional peptides based on natural protein structures (26)(27)(28)(29)(30), the present study pioneered a novel "reverse biomimetic approach" to reveal the function of natural proteins based on artificial peptide structures.…”

Section: Discussionmentioning

confidence: 99%

Histidine-rich protein 2: a new pathogenic factor of Plasmodium falciparum malaria

Iwasaki

Shimoda

Kanayama

et al. 2021

Preprint

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Plasmodium falciparum causes serious malaria symptoms; when this protozoan parasite infects human erythrocytes, it produces and secretes large amounts of histidine-rich protein 2 (PfHRP2) into human blood. Thus, PfHRP2 is a well-known diagnostic marker for malaria infection. Here, however, we also identified PfHRP2 as a pathogenic factor produced by P. falciparum. PfHRP2 showed cell penetration and cytotoxicity against various human cells. In particular, PfHRP2 showed significant cytotoxicity over 5 days at the same concentration as in P. falciparum-infected patients’ blood (90–100 nM). This result is consistent with the mortality rate of P. falciparum malaria, which increases rapidly in untreated cases for 3–7 days. In addition, the cell penetration and cytotoxicity of PfHRP2 increased 2.5- and 2.6-fold, respectively, in the absence of serum, which suggests that low serum protein concentrations (occurring during malnutrition, for example) increase the risk of adverse effects from PfHRP2 (consistent with malnutrition increasing the lethality of malaria infection). We also showed that PfHRP2 bound to Ca2+ ions, localized to intracellular lysosomes, increased lysosomal Ca2+ levels, and inhibited the basal level of autophagy by inhibiting autolysosome formation. Furthermore, the Ca2+-dependent cytotoxicity of PfHRP2 was suppressed by the metal ion chelator ethylenediaminetetraacetic acid (EDTA). In summary, our findings suggest that PfHRP2 acts as a pathogenic factor in P. falciparum-infected patients and is associated with the exacerbation of malaria. Furthermore, EDTA is a promising candidate as a therapeutic agent for the suppression of PfHRP2 pathogenicity. Overall, this study provides new insights into P. falciparum malaria pathogenesis and treatment.

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Section: Discussionmentioning

confidence: 99%

Histidine-rich protein 2: a new pathogenic factor of Plasmodium falciparum malaria

Iwasaki

Shimoda

Kanayama

et al. 2021

Preprint

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“…( 2 ), ( 3 ), and ( 4 ). As the change in entropy term does not affect the relative binding energy of ligands, it was neglected [ 34 ]. …”

Section: Methodsmentioning

confidence: 99%

Identification of some dietary flavonoids as potential inhibitors of TMPRSS2 through protein–ligand interaction studies and binding free energy calculations

Varughese

Kavitha

et al. 2022

Struct Chem

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The continuing threat of COVID-19 and deaths need an urgent cost-effective pharmacological approach. Here, we examine the inhibitory activity of a group of dietary bioactive flavonoids against the human protease TMPRSS2, which plays a major role in SARS CoV-2 viral entry. After the molecular docking studies of a large number of flavonoids, four compounds with high binding scores were selected and studied in detail. The binding affinities of these four ligands, Amentoflavone, Narirutin, Eriocitrin, and Naringin, at the active site of the TMPRSS2 target, were investigated using MD simulations followed by MM-PBSA binding energy calculations. From the studies, a number of significant hydrophobic and hydrogen bonding interactions between the ligands and binding site amino residues of TMPRSS2 are identified which showcase their excellent inhibitory activity against TMPRSS2. Among these ligands, Amentoflavone and Narirutin showed MM-PBSA binding energy values of −155.57 and −139.71 kJ/mol, respectively. Our previous studies of the inhibitory activity of these compounds against the main protease of SARS-COV2 and the present study on TMPRSS2 strongly highlighted that Amentoflavone and Naringin can exhibit promising multi-target activity against SARS-CoV-2. Moreover, due to their wide availability, no side effects, and low cost, these compounds could be recommended as dietary supplements for COVID patients or for the development of SARS-CoV-2 treatments. Supplementary Information The online version contains supplementary material available at 10.1007/s11224-022-01955-7.

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“…Instead of considering absolute binding free energy, we focused on the contribution of individual residues of protein and ligands to the individual components of E MM and Gsolv terms given in Equations (2, 3, and 4). As the change in entropy term does not affect the relative binding energy of ligands, it was neglected [33].…”

Section: Mm-pbsa Binding Free Energy Calculationsmentioning

confidence: 99%

Identification of Some Dietary Flavonoids as Potential Inhibitors of TMPRSS2 Through Protein-ligand Interaction Studies and Binding Free Energy Calculations

Varughese

Kavitha

Sindhu³

et al. 2022

Preprint

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The alarming increase in COVID-19 cases and deaths calls for an urgent cost-effective pharmacological approach. Here, we examine the inhibitory activity of a group of dietary bioactive flavonoids against the human protease TMPRSS2, which plays a major role in SARS CoV-2 viral entry. After the molecular docking studies of a large number of flavonoids, four compounds with high binding scores were selected and studied in detail. The binding affinities of these four ligands, Amentoflavone, Narirutin, Eriocitrin, and Naringin, at the active site of TMPRSS2 target were investigated using MD simulations followed by MM-PBSA binding energy calculations. From the studies, a number of significant hydrophobic and hydrogen bonding interactions between the ligands and binding site amino residues of TMPRSS2 are identified which showcase their excellent inhibitory activity against TMPRSS2. Among these ligands, Amentoflavone and Narirutin showed MM-PBSA binding energy values of -155.48 and -138.13 kJ/mol respectively. Our previous studies of the inhibitory activity of these compounds against main protease of SARS-COV2 and the present study on TMPRSS2 strongly highlighted that Amentoflavone and Naringin can exhibit promising multi-target activity against SARS-CoV-2. Moreover, due to their wide availability, no side effects and low cost, these compounds could be recommended as dietary supplements for COVID patients or for the development of SARS-CoV-2 treatments.

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Biomimetic Design of Peptide Neutralizer of Ebola Virus with Molecular Simulation

Cited by 19 publications

References 42 publications

Histidine-rich protein 2: a new pathogenic factor of Plasmodium falciparum malaria

Histidine-rich protein 2: a new pathogenic factor of Plasmodium falciparum malaria

Identification of some dietary flavonoids as potential inhibitors of TMPRSS2 through protein–ligand interaction studies and binding free energy calculations

Identification of Some Dietary Flavonoids as Potential Inhibitors of TMPRSS2 Through Protein-ligand Interaction Studies and Binding Free Energy Calculations

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