An RNA-dependent RNA polymerase inhibitor for tick-borne encephalitis virus

Gejji, Varun; Svoboda, Pavel; Štefánik, Michal; Wang, Haoqi; Salát, Jiřı́; Eyer, Luděk; Růžek, Daniel; Fernando, Sandun

doi:10.1016/j.virol.2020.03.006

Cited by 10 publications

(5 citation statements)

References 39 publications

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“…However, these observations concern immune cells, which reflection in the plasma or CSF has not been described in the literature yet. A natural reduction in ATP synthesis and hydrolysis in nerve cells in response to TBE could significantly limit viral replication 46 . Therefore, it is not clear, whether the observed decreased level of mentioned proteins in CSF of TBE patients may be correlated with the metabolism of immune cells, or it depends on other factors caused indirectly by the virus or connected with body's defense response.…”

Section: Discussionmentioning

confidence: 99%

Changes in cerebrospinal fluid proteome of patients with tick‐borne encephalitis

Gęgotek,

Moniuszko‐Malinowska,

Groth

et al. 2024

Journal of Medical Virology

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Tick‐borne encephalitis (TBE) is one of the main diseases transmitted by ticks, the incidence of which is increasing. Moreover, its diagnosis and therapy are often long and difficult according to nonspecific symptoms and complex etiology. This study aimed to observe changes in the proteome of cerebrospinal fluid from TBE patients. Cerebrospinal fluid (CSF) of TBE patients (n = 20) and healthy individuals (n = 10) was analyzed using a proteomic approach (QExactiveHF‐Orbitrap mass spectrometer) and zymography. Obtained results show that in CSF of TBE patients, the top‐upregulated proteins are involved in pro‐inflammatory reaction (interleukins), as well as antioxidant/protective response (peroxiredoxins, heat shock proteins). Moreover, changes in the proteome of CSF are not only the result of this disease development, but they can also be an indicator of its course. This mainly applies to proteins involved in proteolysis including serpins and metalloproteinases, whose activity is proportional to the length of patients' convalescence. The obtained proteomic data strongly direct attention to the changes caused by the development of TBE to antioxidant, pro‐inflammatory, and proteolytic proteins, knowledge about which can significantly contribute to faster and more accurate diagnosis of various clinical forms of TBE.

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Section: Discussionmentioning

confidence: 99%

Changes in cerebrospinal fluid proteome of patients with tick‐borne encephalitis

Gęgotek,

Moniuszko‐Malinowska,

Groth

et al. 2024

Journal of Medical Virology

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“…While the lack of flavivirus RdRp structures in their catalytically competent state represents a challenge for structure-based drug discovery approaches, a recent structure of TBEV RdRp helped to identify the differences in catalytic sites between tick-borne and mosquito-borne flaviviruses. These differences were shown to be vital in host recognition, expanding the known RdRp roles in the infection cycle [45,57].…”

Section: Drug-repurposing and Computational Structure-based Drug Designmentioning

confidence: 99%

Virus structure and structure-based antivirals

Plavec

Pöhner

Poso

et al. 2021

Current Opinion in Virology

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“…Enhanced Ligand Exploration and Interaction Recognition Algorithm (ELIXIR-A) [38][39][40][41] (ELIXIR-A) was used for isolating pharmacophore points based on the analyses of interactions between VP35 and probe molecules. ELIXIR-A is an in-house pharmacophore screening algorithm that recognizes pharmacophoric features, i.e., the ensemble of steric, electrostatic, and hydrophobic properties that are crucial for optimum supramolecular interactions with the target receptor to inhibit its biological activity.…”

Section: Pharmacophore Identificationmentioning

confidence: 99%

Impurity D of Anticancer Drug Fulvestrant as a Potential Multifunctional Inhibitor for the Marburg Virus

Wang¹,

Mulgaonkar²,

Mallawarachchi³

et al. 2021

Pharmacophore

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A commonality between viruses and cancer is their ability to seize cellular machinery to rapidly proliferate while suppressing the host's innate immune response. Using probe molecules, specific sites within the virion protein 35 (VP35) of the Marburg virus that have a high affinity to dsRNA (also known as the interferon inhibitory domain, IID), RNA-dependent RNA polymerase (RdRp), and nucleoside triphosphates (NTPs) were identified in silico. Using the dsRNA-binding site as the target, three potential drug molecules FID, CBSMA, and DOCHE were screened. We discovered that FID has a unique ability to simultaneously bind to all the three key binding domains with high affinitya property that none of the other screened drug-like candidates possessed. The ability of FID to bind onto multiple domains of VP35 is significant since this provides the potential to thwart a viral infection from several fronts simultaneously using a single drug to combat rapidly mutating viruses.

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An RNA-dependent RNA polymerase inhibitor for tick-borne encephalitis virus

Cited by 10 publications

References 39 publications

Changes in cerebrospinal fluid proteome of patients with tick‐borne encephalitis

Changes in cerebrospinal fluid proteome of patients with tick‐borne encephalitis

Virus structure and structure-based antivirals

Impurity D of Anticancer Drug Fulvestrant as a Potential Multifunctional Inhibitor for the Marburg Virus

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