antiviral activity of pomegranate (𝑃𝑢𝑛𝑖𝑐𝑎 𝑔𝑟𝑎𝑛𝑎𝑡𝑢𝑚) extract against denv-3: 𝐼𝑛 𝑆𝑖𝑙𝑖𝑐𝑜 and 𝐼𝑛 𝑉𝑖𝑡𝑟𝑜 study

Dengue virus infection is one of the cases that is still a global health problem caused by the dengue virus (denv). until now, no specific drug therapy can be used to inhibit virus replication. pomegranate is a fruit with good biological activity for health, one of which is antiviral activity. this study aims to determine the antiviral activity of dengue virus (denv-3) in vitro and in silico. pomegranate was extracted using 50% and 75% methanol, with a combination of fruit-seed (fs), peel (p), and peel-fruit-seed (pfs) extracts. antiviral activity and mtt assay were carried out on vero cell. in silico was performed on the ns5 protein complex (pdb id: 5jjs). the results of the mtt assay showed that the pfs50 extract had the best cytotoxic activity with a cc50 value of 1085.73 µg/ml. the best antiviral activity came from the fs-75 extract with an ec50 value of 1.97 µg/ml. the results of molecular docking showed that the compounds contained in pomegranate fruit extract were able to bind to the ns5 denv-3 protein complex. ellagitannin, pelletierine, punicalagin, anthocyanin, and epigallocatechin acid had the best binding energy (δg) values. these compounds interact by forming hydrogen bonds, hydrophobic bonds, and electrostatic bonds with different amino acid residues in the c-terminal domain of the ns5 protein. of the five compounds, only anthocyanin and pelletierine compounds meet the parameters of lipinski’s five laws, so that further testing can be carried out for use as oral denv drug candidates.