Insights into Inhibitory Effects of Lapachol against Zika Virus
4 affiliations
- 1Federal University of Uberlândia (UFU) , , , ,
- 2Federal University of Minas Gerais, Institute of Biological Sciences, Department of Genetics, Ecology and Evolution , , ,
- 3Federal University of Triângulo Mineiro , , ,
- 4University of São Paulo , , ,
Abstract
The reemergence of Zika virus (ZIKV) in 2015 and its association with severe neurological manifestations highlighted the urgent need for effective antiviral therapies, which, despite extensive efforts, remain unavailable. Lapachol, a 1,4-naphthoquinone compound abundant in Brazilian plant species, seems to be a promising candidate as an antiviral agent since its activity against other RNA viruses, as well as other human pathogens, including reported activity against Epstein–Barr virus and inhibition of herpes simplex virus type 1 by a lapachol-derived compound. Here, we investigated the activity of lapachol in inhibiting ZIKV replication by employing the wild-type strain ZIKVPE243. Lapachol exhibited potent inhibition of ZIKV with an EC50 of 3 μM and selectivity index of 50. Mechanistic assays suggest that its main action is exerted through postentry inhibition of viral replication, possibly through the blockage of the catalytic sites of NS2B-NS3 protease and NS5 polymerase. Biochemical enzymatic assays confirmed that lapachol inhibits NS2B-NS3 protease and NS5 polymerase activities, being complemented by molecular docking analyses. A protective effect was noted when cells were treated prior to infection, and lapachol was found to induce ROS formation in vitro, indicating that several antiviral mechanisms may be involved, including the initiation of an oxidative stress response that can affect viral particles. Overall, these findings shed light on the potential of lapachol to be used for the development of ZIKV inhibitors, especially targeting postentry stages of virus replication.
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BibTeX
@article{reyes2026insights,
title = {{Insights into Inhibitory Effects of Lapachol against Zika Virus}},
author = {Stephanie Paola Borjas Reyes and Natasha Marques Cassani and João Victor Rodrigues Dutra and Maria Eduarda Trevisan Aguillar da Silva and Nathalya Cristina de Moraes Roso Mesquita and Caroline Martins Mota and Tiago Wilson Patriarca Mineo and Glaucius Oliva and Rafael Victorio Carvalho Guido and Bruno Amaral Meireles and Diego Pandeló José and Ana Carolina Gomes Jardim},
journal = {ACS Omega},
year = {2026},
month = oct,
doi = {10.1021/acsomega.6c04563},
url = {https://pubs.acs.org/acsodf/article/11/41/62804/5444807/Insights-into-Inhibitory-Effects-of-Lapachol},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Insights into Inhibitory Effects of Lapachol against Zika Virus
AU - Stephanie Paola Borjas Reyes
AU - Natasha Marques Cassani
AU - João Victor Rodrigues Dutra
AU - Maria Eduarda Trevisan Aguillar da Silva
AU - Nathalya Cristina de Moraes Roso Mesquita
AU - Caroline Martins Mota
AU - Tiago Wilson Patriarca Mineo
AU - Glaucius Oliva
AU - Rafael Victorio Carvalho Guido
AU - Bruno Amaral Meireles
AU - Diego Pandeló José
AU - Ana Carolina Gomes Jardim
PY - 2026
DA - 2026/10/05
JO - ACS Omega
DO - 10.1021/acsomega.6c04563
UR - https://pubs.acs.org/acsodf/article/11/41/62804/5444807/Insights-into-Inhibitory-Effects-of-Lapachol
AB - The reemergence of Zika virus (ZIKV) in 2015 and its association with severe neurological manifestations highlighted the urgent need for effective antiviral therapies, which, despite extensive efforts, remain unavailable. Lapachol, a 1,4-naphthoquinone compound abundant in Brazilian plant species, seems to be a promising candidate as an antiviral agent since its activity against other RNA viruses, as well as other human pathogens, including reported activity against Epstein–Barr virus and inhibition of herpes simplex virus type 1 by a lapachol-derived compound. Here, we investigated the activity of lapachol in inhibiting ZIKV replication by employing the wild-type strain ZIKVPE243. Lapachol exhibited potent inhibition of ZIKV with an EC50 of 3 μM and selectivity index of 50. Mechanistic assays suggest that its main action is exerted through postentry inhibition of viral replication, possibly through the blockage of the catalytic sites of NS2B-NS3 protease and NS5 polymerase. Biochemical enzymatic assays confirmed that lapachol inhibits NS2B-NS3 protease and NS5 polymerase activities, being complemented by molecular docking analyses. A protective effect was noted when cells were treated prior to infection, and lapachol was found to induce ROS formation in vitro, indicating that several antiviral mechanisms may be involved, including the initiation of an oxidative stress response that can affect viral particles. Overall, these findings shed light on the potential of lapachol to be used for the development of ZIKV inhibitors, especially targeting postentry stages of virus replication.
SN - 2470-1343
ER -