Repurposing FDA-Approved Drugs as Hendra Virus RNA-Dependent RNA Polymerase Inhibitors: A Comprehensive Computational Drug Discovery Approach
Wedi'i Gadw mewn:
| Cyhoeddwyd yn: | Viruses vol. 17, no. 12 (2025), p. 1613-1633 |
|---|---|
| Prif Awdur: | |
| Awduron Eraill: | , , , , , , |
| Cyhoeddwyd: |
MDPI AG
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| Pynciau: | |
| Mynediad Ar-lein: | Citation/Abstract Full Text + Graphics Full Text - PDF |
| Tagiau: |
Dim Tagiau, Byddwch y cyntaf i dagio'r cofnod hwn!
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MARC
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| 001 | 3286359097 | ||
| 003 | UK-CbPIL | ||
| 022 | |a 1999-4915 | ||
| 024 | 7 | |a 10.3390/v17121613 |2 doi | |
| 035 | |a 3286359097 | ||
| 045 | 2 | |b d20250101 |b d20251231 | |
| 084 | |a 231640 |2 nlm | ||
| 100 | 1 | |a Lalu, Anjana C | |
| 245 | 1 | |a Repurposing FDA-Approved Drugs as Hendra Virus RNA-Dependent RNA Polymerase Inhibitors: A Comprehensive Computational Drug Discovery Approach | |
| 260 | |b MDPI AG |c 2025 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a Hendra virus (HeV) is a highly pathogenic zoonotic paramyxovirus that poses a serious threat to human and equine health, yet no approved antivirals or vaccines currently exist. RNA-dependent RNA polymerase (RdRp) of Hendra virus represents a critical and attractive target for antiviral drug development, given its essential role in both viral genome replication and mRNA transcription. Due to the lack of a human homolog, it is more druggable and less likely to cause host toxicity. Its sequence conservation among related paramyxoviruses further highlights its potential for the development of broad-spectrum inhibitors. This study offers the first comprehensive computational analysis of the Hendra virus RdRp, potentially promising FDA-approved drugs as possible inhibitors. A homology model of RdRp was generated in the absence of experimental three-dimensional (3D) structure, followed by virtual screening and molecular dynamics (MD) simulations to evaluate the drug binding and stability. Based on the highest energy, four FDA-approved drugs selected were menadiol diphosphate (−49.88 kcal/mol), masoprocol (−39.69 kcal/mol), pamidronic acid (−34.29 kcal/mol), and dinoprostone (−46.90 kcal/mol). Furthermore, these compounds exhibited significant interactions with the catalytic GDNE motif. With strong conformational stability and pharmacokinetic profile, masoprocol and menadiol diphosphate showed the most stable and energetically favorable interactions within the RdRp active site. These findings suggest their potential as repurposed therapeutic candidates against Hendra virus infection and they provide a structural basis for the development of broad-spectrum paramyxovirus inhibitors, justifying additional experimental confirmation. | |
| 610 | 4 | |a Food & Drug Administration--FDA | |
| 651 | 4 | |a Australia | |
| 653 | |a Physiology | ||
| 653 | |a RNA polymerase | ||
| 653 | |a RNA-directed RNA polymerase | ||
| 653 | |a Toxicity | ||
| 653 | |a Binding sites | ||
| 653 | |a Hydrogen | ||
| 653 | |a Drug development | ||
| 653 | |a Computer applications | ||
| 653 | |a DNA-directed RNA polymerase | ||
| 653 | |a Antiviral agents | ||
| 653 | |a Bioavailability | ||
| 653 | |a Proteins | ||
| 653 | |a Crystal structure | ||
| 653 | |a Simulation | ||
| 653 | |a Fatalities | ||
| 653 | |a RNA viruses | ||
| 653 | |a Pharmacokinetics | ||
| 653 | |a FDA approval | ||
| 653 | |a Pamidronic acid | ||
| 653 | |a Conserved sequence | ||
| 653 | |a Bisphosphonates | ||
| 653 | |a Ligands | ||
| 653 | |a Viruses | ||
| 653 | |a Homology | ||
| 700 | 1 | |a Kundil, Varun Thachan | |
| 700 | 1 | |a Joseph Bristow Ben | |
| 700 | 1 | |a Dev Radul R. | |
| 700 | 1 | |a Amritha, Thaikkad | |
| 700 | 1 | |a Subair Suhail | |
| 700 | 1 | |a Raju Rajesh | |
| 700 | 1 | |a Abhithaj, Jayanandan | |
| 773 | 0 | |t Viruses |g vol. 17, no. 12 (2025), p. 1613-1633 | |
| 786 | 0 | |d ProQuest |t Health & Medical Collection | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/3286359097/abstract/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text + Graphics |u https://www.proquest.com/docview/3286359097/fulltextwithgraphics/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/3286359097/fulltextPDF/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |