The Antiviral Effect of Indonesian Medicinal Plant Extracts Against Dengue Virus In Vitro and In Silico

Abstract

Dengue infections are still a worldwide burden, especially in Indonesia. There is no specific medication against the dengue virus. Recently, many types of research have been conducted to discover a new drug for dengue virus using natural resource extracts. Indonesia, as a tropical country, has a wide biodiversity. There are several medicinal plants in Indonesia that are believed to possess anti-dengue activity, such as Myristica fatua, Cymbopogon citratus, and Acorus calamus plants. We conducted an in vitro laboratory experiment of several extracts from Indonesian herbs combined with in silico analysis. The extracts were evaluated for safety and antiviral activity in Huh7it-1 cell lines, using a single dose of 20 µg/mL and dose-dependent (5, 10, 20, 40, 80 and 160 µg/mL) of plant extracts against dengue virus serotype 2 (DENV-2) NGC strain. The DMSO 0.1% was used as a negative control. The cytotoxic aspect was assessed by counting the cell viability, while the antiviral activity was calculated by counting the average inhibition. The selectivity index (SI) of plant extracts were performed from a ratio of CC50/EC50 value. In silico analysis was conducted to determine the free energy of binding between NS5 of dengue virus with bioactive compounds contained in Myristica fatua, Cymbopogon citratus and Acorus calamus extract plants. We determined that all extracts were not toxic against Huh7it-1 cell lines. The methanolic extracts of A. calamus, C. citratus, and M. fatua showed inhibition of DENV-2 at a dose of 20 µg/mL to 96.5%, 98.9%, and 122.7%, respectively. The dose-dependent effects showed that M. fatua has the best inhibition activity towards DENV-2. Molecular docking result showed that artesunic acid within M. fatua has the best free energy of binding (−7.2 kcal/mol), followed by homoegonol (−7.1 kcal/mol) which was slightly different from artesunic acid among others. The methanolic extracts of A. calamus, C. citratus, and M. fatua showed prospective anti-dengue activities both in vitro and in silico. Future research should be conducted to find the pure extracts of all useful herbs as a new candidate of antiviral drug.

Phytochemicals as Antiviral Agents: Recent Updates

“…These flavonoids were found to be potential inhibitors of H1N1 neuraminidase and thus inhibited the growth of the virus (Bang et al 2016). More recently, the anti-dengue activity of plants found in Indonesia (Myristica fatua, Cymbopogon citratus, and Acorus calamus) was observed by Rosmalena et al (2019). They have performed in silico as well as in vitro experiments to elucidate the antiviral activity against dengue virus serotype 2 (DENV-2).…”

“…Although the solvent extracts of all the plants showed the inhibitory effect, the highest inhibition was recorded for the methanolic extracts of M. fatua. Hence, they suggested the plant for further exploration to make use of it in the herbal formulations in the treatment of dengue virus (Rosmalena et al 2019). Moreover, by using in silico studies, Anusuya and co-workers have reported that some of the phytocompounds, such as 5-hydroxy-3,3′,4′,6,7,8-hexamethylflavone, 4′,5,6,7-tetramethylflavone, and 7″-methylamentoflavone, possess the potential of inhibiting dengue virus (Anusuya and Gromiha 2019).…”

Molecular Docking Analyses of Phytochemicals Obtained from African Antiviral Herbal Plants Exhibit Inhibitory Activity against Therapeutic Targets of SARS-CoV-2

“…Herein we also first report docking studies showing neral (citral) phytochemical from lemongrass as a potent inhibitor of SARS-CoV-2 3C-like protease (main protease). The bioactive compounds of lemongrass have been shown to have antiviral activity on the arbovirus dengue virus (Rosmalena et al, 2019) and nonenveloped enterovirus norovirus (Gilling et al, 2014).…”

In vitro activity evaluation ofLippia albaessential oil against Zika virus

“…Molecular docking predicts the high-affinity binding sites of a protein-ligand complex using three-dimensional structure through in silico assays (34). Molecular docking analysis of the chemical compounds found in the essential oil to Lippia alba against non-structural and structural-proteins of ZIKV has shown a high affinity of coupling with geraniol acetate, bicyclosesquiphellandrene, α-copaene, βbourbonene, geraniol, geranial, germacrene and caryophyllene oxide, being these possible candidates drugs against ZIKV (35)(36)(37). In vitro, beta-caryophyllene has antiviral activity against the non-structural protein NS1 of DENV 2 (38) and citral has antiviral activity against YFV and DENV 2 (27,38).…”