Date of Completion

2022

Document Type

Thesis

Degree Name

Bachelor of Science in Biochemistry

Keywords

Nirmatrelvir, SARS CoV-2, Main protease

Abstract

A pandemic caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) is rapidly spreading and poses a serious threat to the health of the world’s population. SARS-CoV2 has an enzyme called Mpro which aids in the replication of the virus. With the development of Paxlovid by Pfizer, an oral protease inhibitor called nirmatrelvir is used as a reference to design a variety of derivatives. The study evaluated the potential of nirmatrelvir derivatives in treating viral infection through in silico studies with the utilization of UCSF Chimera and AutoDock Vina, which obtained the docking results of the structures against SARS-CoV-2 main protease. Only 6 out of 35 ligands posed as potential inhibitors of Mpro wherein derivative 25 has the most negative docking score of -8.8 kcal/mol while derivatives 21, 26, 31, 34, and 35 had a docking score of -7.6, -7,6, -7.7, -7.6, and 7.7, respectively. In comparison with the reference drug; nirmatrelvir and molnupiravir, had docking scores of -7.7 kcal/mol and -6.6 kcal/mol, respectively. In order to gain a clearer understanding of how the ligands interact with the receptor, the top 6 ligands with the most negative binding affinity were assessed using the BIOVIA Discovery Studio Visualizer. The pharmacological characteristics of the derivatives were then examined using SwissADME and PASSOnline, which showed that the top ligands did not possess any toxic properties. With reference to its low binding affinity, good bioavailability, and non-toxic biological activity, this suggests that derivative 25 has the greatest potential for inhibiting Mpro and is a promising compound for future drug discovery. Design of new derivatives in reference to derivative 25 that will show a more negative binding energy than -8.8 kcal/mol, and conduct of in vivo and in vitro experiments are highly recommended to further evaluate reliable results in drug discovery.

First Advisor

Margel Bonifacio

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