Date of Completion

2023

Document Type

Thesis

Degree Name

Bachelor of Science in Biochemistry

Keywords

DENV-2, NS5, RdRp, Drug Repurposing, Geneticin, Minocycline, Chloroquine, Primaquine, Castanospermine, Deoxynojirimycin, Rosiglitazone

Abstract

Dengue is a virus that belongs to the Flaviviridae family which consists of singlestranded, positive, enveloped RNA that comes from hematophagous arthropods such as mosquitoes. The genome of DENV-2 contains several nonstructural proteins (NS) specifically the NS5 which contains RNA-dependent RNA polymerase (RdRp) domain which plays a role in replication and transcription of the genome and a methyltransferase (MTase) domain for efficient DNA translation. Currently, there are no clinically approved antiviral drugs against DENV-2 infections. In this study, antibiotic drugs (Geneticin and Minocycline), antiparasitic drugs (Chloroquine and Primaquine), and antidiabetic drugs (Castanospermine, Deoxynojirimycin, and Rosiglitazone) were repurposed as antiviral drug against DENV-2. UCSF Chimera was used for docking. Biovia was used to determine interactions between the drugs and amino acid residues. Pro Tox II was used to determine toxicity and SwissADME was used to determine bioavailability of the drugs. Presence or addition of carboxyl, amine, and hydroxyl groups helped in decreasing the binding energy of Geneticin, Minocycline, Chloroquine, Primaquine, and Rosiglitazone, while aromatic rings (benzene) for Castanospermine and Deoxynojirimycin. The toxicity of the successful modifications increased in class and in LD50 value, making all modified drugs little to non-toxic. The bioavailability resulted mostly as ready for oral intake except for most modified Geneticin and Minocycline and a few modified Deoxynojirimycin and Rosiglitazone which were suggested for alternative route (intravenous or via inhalation). The modification that stood out most was Deoxynojirimycin modification 31 due to its high LD50 value (12,400mg/kg) and bioavailability (oral intake) along with 1.226-unit difference in binding energy from the reference. The overall result produced potential anti-dengue virus drugs that are safe for intake though caution with the amount would be necessary due to their specific LD50 values. Further in vitro testing can be conducted to determine the efficacy of these drugs as potential anti-dengue virus drugs.

First Advisor

Walter Aljohn T. Espiritu

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