Brown Monochrome Simple Minimalist Research Project Final Defense Presentation Template

IN SILICO SCREENING OF COMPOUNDS FROM ANNONA MURICATA AS POTENTIAL DENGUE NON-STRUCTURAL PROTEIN 5 (NS5) INHIBITOR.

2. UNIVERSITI TEKNOLOGI MARA (UITM) SHAH ALAM. Problem Statement.

2. DENGUE i . Dengue virus- human pathogen carried by mosquitoes which belongs to the Flaviviridae family and genus Flavivirus ii. Consist of 3 Structural and 7 non-structural protein Non-Structural Protein 5 (NS5) i . Serves as an RNA dependent RNA polymerase ( RdRp ) ii. Serve as RNA methyltransferase enzyme ( MTase ) Annona Muricata i . Genus- Annona, family- Annonaceae ii. Its fruit juice and leaf or branch infusions can treat many types of disease iii. Rich in flavonoids, alkaloids, acetogenins , and phenolic compounds.

2. DENGUE i . Dengue virus- human pathogen carried by mosquitoes which belongs to the Flaviviridae family and genus Flavivirus ii. Consist of 3 Structural and 7 non-structural protein Non-Structural Protein 5 (NS5) i . Serves as an RNA dependent RNA polymerase ( RdRp ) ii. Serve as RNA methyltransferase enzyme ( MTase ) Annona Muricata i . Genus- Annona, family- Annonaceae ii. Its fruit juice and leaf or branch infusions can treat many types of disease iii. Rich in flavonoids, alkaloids, acetogenins , and phenolic compounds.

2. Dengue become much more common Malaysia-forecasted number of cases, dengue infection is expected to be 4 times higher in 2020 and nearly 6 times higher in 2040 Annona muricata has been tested against dengue virus type 2- no compound reported to inhibit NS5 protease Time consuming, and has a low testing capacity Compounds with high cytotoxicity cannot be tested..

2. UNIVERSITI TEKNOLOGI MARA (UITM) SHAH ALAM. SIGNIFICANCE OF STUDY.

RESEARCH OBJECTIVES. 1. 2. 3. To identify compounds from Annona muricata leaves that have potential as dengue non-structural protein 5 (NS5) inhibitors through in silico screening method.

LITERATURE REVIEW.

Acetogenins i . Acetogenins are the most common bioactive chemicals in Annona muricata ii. Rich amount of annonaceous acetogenins has been detected in the leaves of A. muricata, with roughly 46 acetogenins identified out of a total of 120 acetogenins Alkaloids i . Alkaloids are organic molecules with basic nitrogen atoms that exist naturally ii. Alkaloids of the isoquinoline , aporphine, and protoberberine types were found to be the most often isolated in A. muricata.

Phenolic Compound i . Annona muricata has been shown to contain 37 phenolic compounds, 34 of which have been isolated from the plant's leaves Other Compound i . Annona muricata contains vitamins, carotenoids, amides, and cyclopeptides, among other substances ii. Leaves, seeds, and fruit pulp all contain vitamins and carotenoids iii. The seeds contain the amide N -p-coumaroyl tyramine as well as cyclopeptides iv. The fruit pulp of A. muricata contains 37 volatile compounds, the majority of which are aromatic and aliphatic esters.

Antiviral i . According to Padma et al., (1998), ethanolic extracts from the stem and bark of A. muricata showed antiviral efficacy in vitro against the Herpes simplex virus ii. Wahab et al., (2018) conducted research on Annona muricata aqueous leaf extract as inhibitor of dengue virus type 2. Pre-treatment and post-treatment test has been done. As a result, the post-treatment test was found to be more effective than the pre-treatment test in terms of antiviral activity..

2. UNIVERSITI TEKNOLOGI MARA (UITM) SHAH ALAM. IN-SILICO STUDIES ON DENGUE NS5 PROTEASE.

RESULTS AND DISCUSSION.

UNIVERSITI TEKNOLOGI MARA (UITM) SHAH ALAM. LibDock Score LibDock Score Ligands RdRp protease NS5 methyltransferase Annomuricin A 163.962 - Annomontacin 177.094 182.83 Annopentocin C 175.448 - Annonacinone 179.32 - cis-Corossolone - 182.995 Muricatocin C - 192.204 Annohexocin - 196.883.

2. UNIVERSITI TEKNOLOGI MARA (UITM) SHAH ALAM. BINDING INTERACTION.

UNIVERSITI TEKNOLOGI MARA (UITM) SHAH ALAM. 2D interaction diagram of Annonacinone with protein 3VWS.

UNIVERSITI TEKNOLOGI MARA (UITM) SHAH ALAM. 2D interaction diagram of Annohexocin with protein 4R8S.

UNIVERSITI TEKNOLOGI MARA (UITM) SHAH ALAM. 2D interaction diagram of Annohexocin with protein 4R8S.

2. ADMET stands for chemical absorption, distribution, metabolism, excretion and toxicity. GI absorption, Blood-Brain Barrier (BBB), P- gp substrate, CYP3A4 inhibitor are among the important parameters of ADME considered when deciding whether the pharmacological molecule is suitable for pharmaceutical applications. GI absorption? Blood-Brain Barrier (BBB)? P- gp substrate? CYP3A4?.

2. ADMET stands for chemical absorption, distribution, metabolism, excretion and toxicity. GI absorption, Blood-Brain Barrier (BBB), P- gp substrate, CYP3A4 inhibitor are among the important parameters of ADME considered when deciding whether the pharmacological molecule is suitable for pharmaceutical applications. GI absorption? Blood-Brain Barrier (BBB)? P- gp substrate? CYP3A4?.

2. UNIVERSITI TEKNOLOGI MARA (UITM) SHAH ALAM. Compounds GI Absorption BBB Permeant P-gp Substrate CYP3A4 Inhibitor Annomuricin A Low No No Yes Annomontacin Low No No Yes Annopentocin C Low No No Yes Annonacinone Low No Yes Yes cis-Corossolone Low No Yes No Muricatocin C Low No No Yes Annohexocin Low No No No.

2. UNIVERSITI TEKNOLOGI MARA (UITM) SHAH ALAM. In order for the molecule to be used as a drug for human, it must comply with Lipinski’s rule, which requires compounds to have a molecular weight of less than 500 g/mol, not more than 10 hydrogen bond acceptors, not more than 5 hydrogen bond donors, and for lipophilicity, a logP value must be less than 5.

2. UNIVERSITI TEKNOLOGI MARA (UITM) SHAH ALAM. Compounds Molecular Weight (g/mol) Number of H-bond Acceptors Number of H-bond Donors Log P Annomuricin A 612.88 8 5 6.23 Annomontacin 624.93 7 4 7.72 Annopentocin C 612.88 8 5 6.16 Annonacinone 594.86 7 3 6.83 cis-Corossolone 578.86 6 2 7.75 Muricatocin C 612.88 8 5 6.17 Annohexocin 628.88 9 6 5.30.

UNIVERSITI TEKNOLOGI MARA (UITM) SHAH ALAM. CONCLUSION AND RECOMMENDATION.

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