Date of Completion
7-2021
Document Type
Thesis
Degree Name
Bachelor of Science in Biochemistry
Keywords
Computer Simulation, HIV Reverse Transcriptase
Abstract
Previous research has shown that alcoholic extracts from the medicinal plant Tetracera scandens contained compounds that exhibited anti-HIV properties, particularly through the inhibition of the reverse transcriptase enzyme activity of the virus. However, the specific compounds responsible for this bioactivity were not identified. This in silico study aimed to determine the binding energy, ADME properties, and toxicity properties of the compounds found within the alcoholic extracts through the use of UCSF Chimera and Autodock Vina, Swiss ADME, and pkCSM, respectively. These tools aided in identifying the compounds that possessed the most potential in inhibiting the activity of the HIV RTase. In line with this, efavirenz, an antiretroviral non-nucleoside reverse transcriptase inhibitor, was used as the reference drug to aid in the comparative evaluation against the compounds of the T. scandens. Ultimately, the compound that performed the best throughout the in silico study was platanic acid. Upon evaluation through UCSF Chimera and Autodock Vina, it scored -20.7 kcal/mol for binding energy, while efavirenz scored - 12.5 kcal/mol. In SwissADME, platanic acid was determined to pass the Lipinski druglikeness filter and scored 0.85 for bioavailability, while efavirenz also passed the Lipinski druglikeness filter and scored 0.55 for bioavailability. As for their performance in pkCSM, both platanic acid and efavirenz displayed no genotoxicity nor hepatotoxicity. However, they both scored low on their maximum recommended tolerated dose (MRTD)—falling below the threshold value of 0.477 log(mg/kg/day)— with platanic acid possessing an MRTD of 0.314 log(mg/kg/day) and efavirenz at an MRTD of 0.111 log(mg/kg/day). These properties lend credence in the use of platanic acid as a potential lead for the development of antiretroviral non-nucleoside reverse transcriptase inhibitors. However, additional verification of these results through further investigative methods, such as the use of molecular dynamics to combat false positives in binding affinity, is highly recommended.
First Advisor
Margel C. Bonifacio
APA Citation
Chand, M. K., Mangubat, P. E. V., & Timbreza, E. G. (2021). In silico evaluation of tetracera scandens secondary metabolites as potential HIV reverse transcriptase inhibitors. [Bachelor's thesis, De La Salle Medical and Health Sciences Institute]. GreenPrints. https://greenprints.dlshsi.edu.ph/bch/93/