In silico Study of Alkaloid Compounds from Native Southeast Asian Plants: the Utilization of Computational Approaches to Determine Drug Candidates against DENV-2

Abstract

Dengue fever, an acute arthropod borne febrile disease, infects 50-100 million people annually. Indonesia is ranked second out of thirty endemic Dengue Hemorrhagic Fever (DHF) countries from 2004-2010. According to Indonesia’s ministry of health, there are 60,296 cases of dengue fever up until April 2024 resulting in 455 deaths.The high infectivity rate and unavailability of drugs that have been clinically proven as a therapy for DENV has prompted the urgent need for drug identification and discovery.Alkaloid containing plants as herbal remedies have been used by many civilizations. Indonesia is ranked the second highest in the number of indigenous medicinal plants in which there are 1000 Indonesian medicinal plants and only 350 have been explored. This indicates that there is a wide possibility of research in the field of therapeutics for dengue virus. The utilization of Computer-aided drug design (CADD) including molecular docking and molecular dynamics simulation through different alkaloid compounds found in medicinal Southeast Asian plants especially Indonesia can lead to a potential drug discovery that may have the potential to counteract DENV based on its interaction with the relevant protein target. The relevant protein target in this study is NS5 of DENV-2 as it is the largest and most conserved protein and DENV-2 is linked to disease severity.