Computational screening of medicinal plant phytochemicals to discover potent pan-serotype inhibitors against dengue virus
| Autor: | Mohammed H. Geesi, Sadaf Abdul Rauf, Abdul Rauf Siddiqi, Faheem Ahmed Khan, Rana Rehan Khalid, Farooq Anwar, Usman Ali Ashfaq, Feng Xing, Muhammad Tahir ul Qamar, Arooma Maryam, Iqra Muneer |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Serotype medicine.drug_class Phytochemicals lcsh:Medicine Biology Dengue virus Viral Nonstructural Proteins medicine.disease_cause Serogroup Antiviral Agents Article Dengue fever 03 medical and health sciences 0302 clinical medicine Drug Discovery medicine Enzyme Inhibitors lcsh:Science NS3 Multidisciplinary Binding Sites Plants Medicinal Drug discovery lcsh:R Serine Endopeptidases Dengue Virus medicine.disease Virology Molecular Docking Simulation 030104 developmental biology Drug development Viral replication lcsh:Q Antiviral drug 030217 neurology & neurosurgery RNA Helicases Protein Binding |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-16 (2019) |
| ISSN: | 2045-2322 |
| Popis: | Emergence of Dengue as one of the deadliest viral diseases prompts the need for development of effective therapeutic agents. Dengue virus (DV) exists in four different serotypes and infection caused by one serotype predisposes its host to another DV serotype heterotypic re-infection. We undertook virtual ligand screening (VLS) to filter compounds against DV that may inhibit inclusively all of its serotypes. Conserved non-structural DV protein targets such as NS1, NS3/NS2B and NS5, which play crucial role in viral replication, infection cycle and host interaction, were selected for screening of vital antiviral drug leads. A dataset of plant based natural antiviral derivatives was developed. Molecular docking was performed to estimate the spatial affinity of target compounds for the active sites of DV’s NS1, NS3/NS2B and NS5 proteins. The drug likeliness of the screened compounds was followed by ADMET analysis whereas the binding behaviors were further elucidated through molecular dynamics (MD) simulation experiments. VLS screened three potential compounds including Canthin-6-one 9-O-beta-glucopyranoside, Kushenol W and Kushenol K which exhibited optimal binding with all the three conserved DV proteins. This study brings forth novel scaffolds against DV serotypes to serve as lead molecules for further optimization and drug development against all DV serotypes with equal effect against multiple disease causing DV proteins. We therefore anticipate that the insights given in the current study could be regarded valuable towards exploration and development of a broad-spectrum natural anti-dengue therapy. |
| Databáze: | OpenAIRE |
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