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Updated: Mar 7, 2026
High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication
Published on: October 30, 2021
Identification of potential inhibitors against the Zika virus using consensus scoring
Abdulmujeeb T Onawole1, Kazeem O Sulaiman1, Rukayat O Adegoke2
1Department of Chemistry, King Fahd University of Petroleum & Minerals, Dhahran, 31261, Saudi Arabia.
Abstract:
The Zika virus (ZIKV) is a life threatening pathogen of zoonotic importance with prevalence in some parts of Africa and America. Unfortunately, there is yet to be a single approved vaccine or antiviral drug to treat the diseases and deformations being caused by the Zika virus infection. In this study, about 36 million compounds from MCULE database were virtually screened against a real matured ZIKV protein using a consensus scoring method to get improved hit rates. The consensus scoring method combined the result from the 25 top ranked molecules from both MCULE and Drug Score eXtended (DSX) docking programs which led to the selection of two hit compounds. The inhibition constant (Ki) values of 0.08 and 0.30μm were obtained for the two selected compounds MCULE-8830369631-0-1 and MCULE-9236850811-0-1 respectively, to remark them as hit compounds. The molecular interactions of the two selected hit compounds with the amino acids (ALA 48, ILE 49, ILE 468 and LEU 472) present in the ZIKV protein indicated that they both have similar binding modes. The result of the computationally predicted physicochemical properties including ADMET for the selected compounds showed their great potential in becoming lead compounds upon optimization and thus could be used in treating the Zika virus diseases.
Insights
Researchers screened 36 million compounds to identify potential Zika virus (ZIKV) treatments. Two promising compounds were found, showing potential for developing new antiviral drugs against ZIKV infection.
Area of Science:
- Virology
- Computational Chemistry
- Drug Discovery
Background:
- Zika virus (ZIKV) poses a significant global health threat, causing severe diseases and birth defects.
- Current therapeutic options for ZIKV infection are limited, with no approved vaccines or antiviral drugs available.
Purpose of the Study:
- To identify novel compounds with potential antiviral activity against Zika virus.
- To virtually screen a large compound library against the ZIKV protein to discover hit compounds.
Main Methods:
- Virtual screening of approximately 36 million compounds from the MCULE database against a mature ZIKV protein.
- Utilized a consensus scoring method combining results from MCULE and Drug Score eXtended (DSX) docking programs.
- Evaluated molecular interactions and predicted physicochemical properties (ADMET) of selected hit compounds.
Main Results:
- Two hit compounds, MCULE-8830369631-0-1 and MCULE-9236850811-0-1, were identified with inhibition constant (Ki) values of 0.08 μm and 0.30 μm, respectively.
- Both compounds exhibited similar binding modes with key amino acids (ALA 48, ILE 49, ILE 468, LEU 472) in the ZIKV protein.
- Predicted physicochemical properties suggest the identified compounds have potential as lead compounds for ZIKV treatment.
Conclusions:
- The identified hit compounds demonstrate promise for the development of novel antiviral therapies against Zika virus.
- Further optimization of these compounds could lead to effective treatments for ZIKV-related diseases and deformations.
