International Journal of Public Health Science (IJPHS) Vol. 13, No. 3, September 2024, pp. 1019~1029 ISSN: 2252-8806, DOI: 10.11591/ijphs.v13i3.23822  1019 Journal homepage: http://ijphs.iaescore.com Interactions and mechanisms of phenolic compounds with human immunodeficiency virus-1 Tat protein Cherry May S. Delos Santos 1 , June Alexis A. Santos 2 , Danilet Vi M. Mendoza 3 1 College of Arts and Sciences, Nueva Ecija University of Science and Technology, Cabanatuan City, Philippines 2 Department of Environment and Natural Resources, Mines and Geosciences Bureau-Region III, San Fernando City, Philippines 3 Department of Natural and Applied Sciences, College of Arts and Sciences, Nueva Ecija University of Science and Technology, Cabanatuan City, Philippines Article Info ABSTRACT Article history: Received Aug 23, 2023 Revised Jan 2, 2024 Accepted Jan 9, 2024 Human immunodeficiency virus remains a serious health threat, with an increase of 24% newly cases globally. Targeting Tat protein is an emerging therapeutic strategy for inhibiting the feedback loop that drives the exponential increase in viral transcription and particle production of the virus. The study aimed to determine the inhibitory potential of phenolic compounds from Ricinus communis L. and Jatropha curcas L., against the Tat C protein using in silico techniques. Phenolic compounds identified from both plants were screened by absorption-distribution-metabolism-excretion (ADME) analysis using drug-likeness prediction. Molecular docking analysis of the compounds with drug-like properties against the receptor and ligand-protein complexes’ analysis and visualization were performed. The results revealed three phenolic compounds with the highest negative binding affinity to the receptor’s active site: ellagic and neochlorogenic acids with - 7.2 kcal/mol and isohemiphloin with -7.3 kcal/mol. The interacting amino acids of the complexes were majorly His13, Lys19, Lys28, Thr64, His65, Gln66, Pro70, Gln72, and Pro73 via non-covalent interactions: hydrogen bonds, hydrophobic, and electrostatic interactions. The identified phenolic compounds provide a core structure that can be candidate for plant-based antiviral drugs development to potentially aiding in the virus’s therapeutic challenge. Keywords: HIV-1 In silico Molecular docking Phenolic compounds Tat protein This is an open access article under the CC BY-SA license. Corresponding Author: Danilet Vi M. Mendoza Department of Natural and Applied Sciences, College of Arts and Sciences Nueva Ecija University of Science and Technology Cabanatuan City, Nueva Ecija, Philippines Email: niletmendoza@yahoo.com 1. INTRODUCTION The human immunodeficiency virus (HIV) remains a major public health concern, with 84.2 million people infected since the epidemic’s inception and approximately 38.4 million people worldwide living with HIV in 2021 with an increase of 24% relative to 2010. According to the World Health Organization (WHO), the African region remains the most severely affected with the highest number of HIV-infected people, approximately 25.6 million; and in the Asia and Pacific Region, the Philippines has the fastest-growing case with a 237% increase in annual new HIV infections from 2010 to 2021. The Department of Health of the Philippines recorded 14, 970 cases of HIV infection in 2022, which is 21% higher than the previous year, and stated that the number of HIV diagnoses in the country fluctuated over the past seven years. This continuous increase in HIV cases necessitates a more aggressive response and increased focus on HIV/AIDS.