Related Experiment Video
Updated: Dec 2, 2025
Analysis of Group IV Viral SSHHPS Using In Vitro and In Silico Methods
Published on: December 21, 2019
An in-silico analysis of ivermectin interaction with potential SARS-CoV-2 targets and host nuclear importin α
Faizul Azam1, Ismail M Taban2,3, Eltayeb E M Eid1
1Department of Pharmaceutical Chemistry & Pharmacognosy, Unaizah College of Pharmacy, Qassim University, Saudi Arabia.
Abstract:
Ivermectin (IVM) is a broad-spectrum antiparasitic agent, having inhibitory potential against wide range of viral infections. It has also been found to hamper SARS-CoV-2 replication in vitro, and its precise mechanism of action against SARS-CoV-2 is yet to be understood. IVM is known to interact with host importin (IMP)α directly and averts interaction with IMPβ1, leading to the prevention of nuclear localization signal (NLS) recognition. Therefore, the current study seeks to employ molecular docking, molecular mechanics generalized Born surface area (MM-GBSA) analysis and molecular dynamics simulation studies for decrypting the binding mode, key interacting residues as well as mechanistic insights on IVM interaction with 15 potential drug targets associated with COVID-19 as well as IMPα. Among all COVID-19 targets, the non-structural protein 9 (Nsp9) exhibited the strongest affinity to IVM showing -5.30 kcal/mol and -84.85 kcal/mol binding energies estimated by AutoDock Vina and MM-GBSA, respectively. However, moderate affinity was accounted for IMPα amounting -6.9 kcal/mol and -66.04 kcal/mol. Stability of the protein-ligand complexes of Nsp9-IVM and IMPα-IVM was ascertained by 100 ns trajectory of all-atom molecular dynamics simulation. Structural conformation of protein in complex with docked IVM exhibited stable root mean square deviation while root mean square fluctuations were also found to be consistent. In silico exploration of the potential targets and their interaction profile with IVM can assist experimental studies as well as designing of COVID-19 drugs. Communicated by Ramaswamy H. Sarma.
Insights
Ivermectin shows strong binding affinity to SARS-CoV-2 non-structural protein 9 (Nsp9) and moderate affinity to importin alpha (IMPα), suggesting potential as a COVID-19 therapeutic. Further in silico analysis supports its drug design potential.
Area of Science:
- Virology
- Computational Biology
- Drug Discovery
Background:
- Ivermectin (IVM), an antiparasitic agent, exhibits inhibitory effects against viral infections, including SARS-CoV-2 replication in vitro.
- The precise mechanism of IVM's action against SARS-CoV-2 remains unclear, although it is known to interfere with host importin alpha (IMPα) and nuclear localization signal (NLS) recognition.
Purpose of the Study:
- To investigate the binding mode and mechanistic insights of Ivermectin (IVM) interaction with 15 potential SARS-CoV-2 drug targets and importin alpha (IMPα).
- To utilize molecular docking, MM-GBSA, and molecular dynamics simulations to analyze IVM's interactions with these targets.
Main Methods:
- Molecular docking simulations using AutoDock Vina.
- Molecular mechanics generalized Born surface area (MM-GBSA) calculations for binding energy estimation.
- 100 ns all-atom molecular dynamics simulations to assess the stability of protein-ligand complexes.
Main Results:
- Ivermectin (IVM) demonstrated the strongest binding affinity to SARS-CoV-2 non-structural protein 9 (Nsp9) (-5.30 kcal/mol AutoDock Vina, -84.85 kcal/mol MM-GBSA).
- Moderate binding affinity was observed between IVM and importin alpha (IMPα) (-6.9 kcal/mol AutoDock Vina, -66.04 kcal/mol MM-GBSA).
- Molecular dynamics simulations confirmed the stability of the Nsp9-IVM and IMPα-IVM complexes.
Conclusions:
- The study identifies Nsp9 as a potential key target for Ivermectin's antiviral activity against SARS-CoV-2.
- In silico findings provide mechanistic insights into IVM's interaction with viral and host factors.
- These computational explorations can guide experimental validation and the development of novel COVID-19 therapeutics.
More Related Videos
06:03Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16
Published on: July 15, 2019
08:31Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
Published on: December 1, 2020
