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Updated: Mar 13, 2026
High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication
Published on: October 30, 2021
Virtual Screening for Potential Inhibitors of NS3 Protein of Zika Virus
Maheswata Sahoo1, Lingaraja Jena1, Sangeeta Daf2
1Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram 442-102, India.
Abstract:
Zika virus (ZIKV) is a mosquito borne pathogen, belongs to Flaviviridae family having a positive-sense single-stranded RNA genome, currently known for causing large epidemics in Brazil. Its infection can cause microcephaly, a serious birth defect during pregnancy. The recent outbreak of ZIKV in February 2016 in Brazil realized it as a major health risk, demands an enhanced surveillance and a need to develop novel drugs against ZIKV. Amodiaquine, prochlorperazine, quinacrine, and berberine are few promising drugs approved by Food and Drug Administration against dengue virus which also belong to Flaviviridae family. In this study, we performed molecular docking analysis of these drugs against nonstructural 3 (NS3) protein of ZIKV. The protease activity of NS3 is necessary for viral replication and its prohibition could be considered as a strategy for treatment of ZIKV infection. Amongst these four drugs, berberine has shown highest binding affinity of -5.8 kcal/mol and it is binding around the active site region of the receptor. Based on the properties of berberine, more similar compounds were retrieved from ZINC database and a structure-based virtual screening was carried out by AutoDock Vina in PyRx 0.8. Best 10 novel drug-like compounds were identified and amongst them ZINC53047591 (2-(benzylsulfanyl)-3-cyclohexyl-3H-spiro[benzo[h]quinazoline-5,1'-cyclopentan]-4(6H)-one) was found to interact with NS3 protein with binding energy of -7.1 kcal/mol and formed H-bonds with Ser135 and Asn152 amino acid residues. Observations made in this study may extend an assuring platform for developing anti-viral competitive inhibitors against ZIKV infection.
Insights
Berberine and novel compounds show potential as Zika virus (ZIKV) inhibitors. Molecular docking identified ZINC53047591 as a promising drug candidate targeting the NS3 protein, offering a new strategy against ZIKV infection.
Area of Science:
- Virology
- Drug Discovery
- Computational Chemistry
Background:
- Zika virus (ZIKV), a mosquito-borne flavivirus, causes epidemics and severe birth defects like microcephaly.
- The 2016 Brazil outbreak highlighted the urgent need for ZIKV surveillance and novel antiviral drugs.
- The NS3 protein's protease activity is crucial for ZIKV replication, making it a key therapeutic target.
Purpose of the Study:
- To identify potential drug candidates against ZIKV by targeting the NS3 protein.
- To evaluate FDA-approved drugs and novel compounds for their binding affinity to ZIKV NS3.
- To explore structure-based virtual screening for discovering new antiviral agents.
Main Methods:
- Molecular docking analysis of amodiaquine, prochlorperazine, quinacrine, and berberine against ZIKV NS3 protein.
- Virtual screening of the ZINC database using AutoDock Vina and PyRx 0.8 based on berberine's properties.
- Identification and binding energy calculation of top-ranking compounds.
Main Results:
- Berberine exhibited the highest binding affinity (-5.8 kcal/mol) among the tested drugs, interacting near the NS3 active site.
- Structure-based virtual screening identified 10 novel drug-like compounds.
- ZINC53047591 demonstrated significant binding energy (-7.1 kcal/mol) and formed hydrogen bonds with key residues (Ser135, Asn152) of the NS3 protein.
Conclusions:
- Berberine and novel compounds show promise as competitive inhibitors of ZIKV NS3.
- ZINC53047591 represents a potential lead compound for developing new antiviral therapies against Zika virus.
- This study provides a foundation for designing effective antiviral agents against ZIKV infection.
