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  1. Article ; Online: Efficiency of membrane fusion inhibitors on different hemagglutinin subtypes: insight from a molecular dynamics simulation perspective.

    Nunthaboot, Nadtanet / Boonma, Thitiya / Rajchakom, Chananya / Nutho, Bodee / Rungrotmongkol, Thanyada

    Journal of biomolecular structure & dynamics

    2024  , Page(s) 1–12

    Abstract: The challenge in vaccine development, along with drug resistance issues, has encouraged the search for new anti-influenza drugs targeting different viral proteins. Hemagglutinin (HA) glycoprotein, crucial in the viral replication cycle, has emerged as a ... ...

    Abstract The challenge in vaccine development, along with drug resistance issues, has encouraged the search for new anti-influenza drugs targeting different viral proteins. Hemagglutinin (HA) glycoprotein, crucial in the viral replication cycle, has emerged as a promising therapeutic target. CBS1117 and JNJ4796 were reported to exhibit similar potencies against infectious group 1 influenza, which included H1 and H5 HAs; however, their potencies were significantly reduced against group 2 HA. This study aims to explore the molecular binding mechanisms and group specificity of these fusion inhibitors against both group 1 (H5) and group 2 (H3) HA influenza viruses using molecular dynamics simulations. CBS1117 and JNJ4796 exhibit stronger interactions with key residues within the H5 HA binding pocket compared to H3-ligand complexes. Hydrogen bonding and hydrophobic interactions involving residues, such as H38
    Language English
    Publishing date 2024-02-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 49157-3
    ISSN 1538-0254 ; 0739-1102
    ISSN (online) 1538-0254
    ISSN 0739-1102
    DOI 10.1080/07391102.2024.2322629
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2093: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Insights into binding molecular mechanism of hemagglutinin H3N2 of influenza virus complexed with arbidol and its derivative: A molecular dynamics simulation perspective.

    Boonma, Thitiya / Soikudrua, Nattharuja / Nutho, Bodee / Rungrotmongkol, Thanyada / Nunthaboot, Nadtanet

    Computational biology and chemistry

    2022  Volume 101, Page(s) 107764

    Abstract: Recently, the H3N2 influenza outbreak has caused serious global public health concern for future control of the next influenza pandemic. Since using current anti-influenza drugs targeting neuraminidase (oseltamivir and zanamivir) and the proton M2 ... ...

    Abstract Recently, the H3N2 influenza outbreak has caused serious global public health concern for future control of the next influenza pandemic. Since using current anti-influenza drugs targeting neuraminidase (oseltamivir and zanamivir) and the proton M2 channel (amantadine and rimantadine) leads to drug resistance, it is essential to seek new anti-viral agents that act on additional viral targets. Hemagglutinin (HA), a glycoprotein embedded in the viral surface and playing a critical role in influenza the viral replication cycle has become an attractive target. This work investigates the molecular binding mechanism of HA H3N2 of influenza virus complexed with the fusion inhibitor, arbidol and its derivative (der-arbidol), by means of molecular dynamics simulation. The result showed that the arbidol derivative could form many and strong hydrogen bonds with the HA surrounding amino acids comprising GLU103
    MeSH term(s) Humans ; Influenza A Virus, H3N2 Subtype ; Hemagglutinins ; Molecular Dynamics Simulation ; Oseltamivir/pharmacology ; Oseltamivir/therapeutic use ; Antiviral Agents/chemistry ; Influenza, Human/drug therapy
    Chemical Substances umifenovir (93M09WW4RU) ; Hemagglutinins ; Oseltamivir (20O93L6F9H) ; Antiviral Agents
    Language English
    Publishing date 2022-08-28
    Publishing country England
    Document type Journal Article
    ISSN 1476-928X
    ISSN (online) 1476-928X
    DOI 10.1016/j.compbiolchem.2022.107764
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Exploring of paritaprevir and glecaprevir resistance due to A156T mutation of HCV NS3/4A protease: molecular dynamics simulation study.

    Boonma, Thitiya / Nutho, Bodee / Darai, Nitchakan / Rungrotmongkol, Thanyada / Nunthaboot, Nadtanet

    Journal of biomolecular structure & dynamics

    2021  Volume 40, Issue 12, Page(s) 5283–5294

    Abstract: Hepatitis C virus (HCV) NS3/4A serine protease is a promising drug target for the discovery of anti-HCV drugs. However, its amino acid mutations, particularly A156T, commonly lead to rapid emergence of drug resistance. Paritaprevir and glecaprevir, the ... ...

    Abstract Hepatitis C virus (HCV) NS3/4A serine protease is a promising drug target for the discovery of anti-HCV drugs. However, its amino acid mutations, particularly A156T, commonly lead to rapid emergence of drug resistance. Paritaprevir and glecaprevir, the newly FDA-approved HCV drugs, exhibit distinct resistance profiles against the A156T mutation of HCV NS3/4A serine protease. To illustrate their different molecular resistance mechanisms, molecular dynamics simulations and binding free energy calculations were carried out on the two compounds complexed with both wild-type (WT) and A156T variants of HCV NS3/4A protease. QM/MM-GBSA-based binding free energy calculations revealed that the binding affinities of paritaprevir and glecaprevir towards A156T NS3/4A were significantly reduced by ∼4 kcal/mol with respect to their WT complexes, which were in line with the experimental resistance folds. Moreover, the relatively weak intermolecular interactions with amino acids such as H57, R155, and T156 of NS3 protein, the steric effect and the destabilized protein binding surface, which is caused by the loss of salt bridge between R123 and D168, are the main contributions for the higher fold-loss in potency of glecaprevir due to A156T mutation. An insight into the difference of molecular mechanism of drug resistance against the A156T substitution among the two classes of serine protease inhibitors could be useful for further optimization of new generation HCV NS3/4A inhibitors with enhanced inhibitory potency.Communicated by Ramaswamy H. Sarma.
    MeSH term(s) Aminoisobutyric Acids ; Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Cyclopropanes ; Drug Resistance, Viral/genetics ; Hepacivirus ; Lactams, Macrocyclic ; Leucine/analogs & derivatives ; Molecular Dynamics Simulation ; Mutation ; Proline/analogs & derivatives ; Protease Inhibitors/pharmacology ; Quinoxalines ; Serine Proteases/genetics ; Serine Proteases/metabolism ; Sulfonamides ; Viral Nonstructural Proteins/chemistry
    Chemical Substances Aminoisobutyric Acids ; Antiviral Agents ; Cyclopropanes ; Lactams, Macrocyclic ; Protease Inhibitors ; Quinoxalines ; Sulfonamides ; Viral Nonstructural Proteins ; Proline (9DLQ4CIU6V) ; Serine Proteases (EC 3.4.-) ; Leucine (GMW67QNF9C) ; glecaprevir (K6BUU8J72P) ; paritaprevir (OU2YM37K86)
    Language English
    Publishing date 2021-01-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 49157-3
    ISSN 1538-0254 ; 0739-1102
    ISSN (online) 1538-0254
    ISSN 0739-1102
    DOI 10.1080/07391102.2020.1869587
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 2093: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Understanding of the drug resistance mechanism of hepatitis C virus NS3/4A to paritaprevir due to D168N/Y mutations: A molecular dynamics simulation perspective.

    Boonma, Thitiya / Nutho, Bodee / Rungrotmongkol, Thanyada / Nunthaboot, Nadtanet

    Computational biology and chemistry

    2019  Volume 83, Page(s) 107154

    Abstract: Hepatitis C virus (HCV) NS3/4A protease is an attractive target for the development of antiviral therapy. However, the evolution of antiviral drug resistance is a major problem for treatment of HCV infected patients. Understanding of drug-resistance ... ...

    Abstract Hepatitis C virus (HCV) NS3/4A protease is an attractive target for the development of antiviral therapy. However, the evolution of antiviral drug resistance is a major problem for treatment of HCV infected patients. Understanding of drug-resistance mechanisms at molecular level is therefore very important for the guidance of further design of antiviral drugs with high efficiency and specificity. Paritaprevir is a potent inhibitor against HCV NS3/4A protease genotype 1a. Unfortunately, this compound is highly susceptible to the substitution at D168 in the protease. In this work, molecular dynamics simulations of paritaprevir complexed with wild-type (WT) and two mutated strains (D168 N and D168Y) were carried out. Due to such mutations, the inhibitor-protein hydrogen bonding between them was weakened and the salt-bridge network among residues R123, R155 and D168 responsible for inhibitor binding was disrupted. Moreover, the per-residue free energy decomposition suggested that the main contributions from key residues such as Q80, V132, K136, G137 and R155 were lost in the D168 N/Y mutations. These lead to a lower binding affinity of paritaprevir for D168 N/Y variants of the HCV NS3/4A protease, consistent with the experimental data. This detailed information could be useful for further design of high potency anti-HCV NS3/4A inhibitors.
    MeSH term(s) Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Drug Resistance, Viral/drug effects ; Hydrogen Bonding ; Intracellular Signaling Peptides and Proteins/antagonists & inhibitors ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Macrocyclic Compounds/chemistry ; Macrocyclic Compounds/pharmacology ; Molecular Dynamics Simulation ; Mutation ; Thermodynamics ; Viral Nonstructural Proteins/antagonists & inhibitors ; Viral Nonstructural Proteins/genetics ; Viral Nonstructural Proteins/metabolism
    Chemical Substances Antiviral Agents ; Intracellular Signaling Peptides and Proteins ; Macrocyclic Compounds ; NS3 protein, hepatitis C virus ; NS4A cofactor peptide, Hepatitis C virus ; Viral Nonstructural Proteins ; paritaprevir (OU2YM37K86)
    Language English
    Publishing date 2019-11-09
    Publishing country England
    Document type Journal Article
    ISSN 1476-928X
    ISSN (online) 1476-928X
    DOI 10.1016/j.compbiolchem.2019.107154
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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