Date of Completion

2022

Document Type

Thesis

Degree Name

Bachelor of Science in Biochemistry

Keywords

COVID-19, Mpro, Lentinula edodes, ADMET, Molecular Docking, In silico

Abstract

In the year 2019, a global pandemic occurred caused by SARS-CoV-2, an infectious virus causing respiratory and cardiovascular illnesses. Through recent studies, the genome information and its structure have been published. The virus contains main protease, an enzyme essential for the replication and transcription of the virus. As an important target for drug design and discovery, the study focused on the secondary metabolites of Lentinula edodes and its derivatives to assess and predict its inhibitory potential against SARS-CoV-2 Mpro. Several softwares and websites were used, namely PubChem, RCSB PDB, UCSF Chimera, Autodock Vina, BIOVIA Discovery Studio Visualizer, MarvinSketch, SwissADME, and PASS online .With the use of in silico studies, the ligands were docked with the Mpro including reference drugs remdesivir, molnupiravir and nirmatrelvir. Out of the secondary metabolites of L. edodes, eritadenine showed a binding affinity of -6.6 kcal/mol, while ergosterol and demethylincisterol A3 had -6.2 kcal/mol. The derivatives acquired higher negative binding results with a value of -8.6 kcal/mol for ergosterol D121, -8.5 kcal/mol for ergosterol S2D18, and -8.2 kcal/mol for eritadenine D90 and D92. The following showed higher negative binding affinity with Mpro compared to the reference drug nirmatrelvir with a binding affinity of -7.1 kcal/mol which was the highest among the reference drugs. ADMET properties were also taken into consideration for the analysis of the ligand. General results reflected low gastrointestinal absorption and 2- 3 violations in the Lipinski’s rule. Lipophilicity results were majority low although there are still possibilities of antiviral activity although not considered high but still present. Ergosterol D121 showed the most negative binding energy of -8.6 kcal/mol though its SWISS adme result showed that it is not a potential oral drug. Ergosterol D121’s toxicity results as well as binding energy makes it the best candidate that showed the most inhibitory effect against the SARS-CoV-2 main protease.

First Advisor

Margel C. Bonifacio

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