In silico studies of antiviral ligands derived from Ganoderma lucidum against dengue type 2 and zika viral proteins / Lim Wui Zhuan
Dengue and Zika infections are mainly transmitted through the bites of Aedes aegypti mosquitoes. Without potential cures or clinically approved antivirals for both infections, the Flaviviruses that cause these infectious diseases will continue to pose health risks, especially to the nations of As...
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| Format: | Thesis |
| Published: |
2024
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| Online Access: | http://studentsrepo.um.edu.my/15820/2/Lim_Wui_Zhuan.pdf http://studentsrepo.um.edu.my/15820/1/Lim_Wui_Zhuan.pdf http://studentsrepo.um.edu.my/15820/ |
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| Summary: | Dengue and Zika infections are mainly transmitted through the bites of Aedes aegypti
mosquitoes. Without potential cures or clinically approved antivirals for both infections,
the Flaviviruses that cause these infectious diseases will continue to pose health risks,
especially to the nations of Asia, Africa and South America. For dengue, it is a
challenging process to find suitable treatment that can eradicate the infections
successfully, as there are multiple serotypes circulating in tropical and subtropical regions
around the world. In this study, the transcriptional changes caused by virus-host
interactions were presented through the identification of differentially expressed genes
(DEGs) and pathway analysis, to gain understanding of the pathogenicity of dengue virus
(DENV) and Zika virus (ZIKV). Based on the enriched pathways in DAVID, KEGG and
Reactome, the biological processes of DEGs in dengue and Zika patients were
concentrated in cell division and DNA replication. DEGs such as MCM2, MCM4, MCM6
and PCNA can serve as potential biomarkers of dengue infections. Surprisingly, a few
up-regulated DEGs in Zika datasets, namely OAS1, OAS2, OAS3 and DDX58, were
associated with other diseases such as measles, Epstein-Barr virus infection, and hepatitis
C. These antiviral interferon-stimulated genes suggested that ZIKA-infected patients
responded to Zika infection primarily by suppressing viral RNA replication. Since cell
cycle and genome replication were highlighted in the pathway analysis, the natural
compounds derived from the antler-shaped fruiting body of Ganoderma lucidum were
screened against the protease and envelope proteins of DENV and ZIKV, to find potential
antivirals that can disrupt the above pathways. Docking results showed that hesperetin
and naringenin were the best ligand candidates to bind at the catalytic site of NS2B-NS3 protease and the hydrophobic pocket of envelope protein, respectively. Their stable
docking conformations and favourable binding free energy showed potential to prevent
the viral replication and fusion processes. Naringenin was also able to target the same
hydrophobic pocket of Zika virus envelope protein, however its binding free energy after
100 ns of simulation was less favourable than the reference ligand. A longer simulation
time might be required to extend the convergence of the trajectories. This study can serve
as a reference for molecular biological experiments in future to confirm the function of
DEGs associated with dengue and Zika infections, as well as the roles of hesperetin and
naringenin in combating the diseases.
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