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Updated: Nov 28, 2025
Analysis of the Lipid Composition of Mycobacteria by Thin Layer Chromatography
Published on: April 16, 2021
Translation of Mycobacterium Survival Strategy to Develop a Lipo-peptide based Fusion Inhibitor*
Avijit Sardar1, Aritraa Lahiri2, Mithila Kamble2
1Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, PIN-741246, India.
Abstract:
The entry of enveloped virus requires the fusion of viral and host cell membranes. An effective fusion inhibitor aiming at impeding such membrane fusion may emerge as a broad-spectrum antiviral agent against a wide range of viral infections. Mycobacterium survives inside the phagosome by inhibiting phagosome-lysosome fusion with the help of a coat protein coronin 1. Structural analysis of coronin 1 and other WD40-repeat protein suggest that the trp-asp (WD) sequence is placed at distorted β-meander motif (more exposed) in coronin 1. The unique structural feature of coronin 1 was explored to identify a simple lipo-peptide sequence (myr-WD), which effectively inhibits membrane fusion by modulating the interfacial order, water penetration, and surface potential. The mycobacterium inspired lipo-dipeptide was successfully tested to combat type 1 influenza virus (H1N1) and murine coronavirus infections as a potential broad-spectrum antiviral agent.
Insights
A novel lipo-peptide, inspired by Mycobacterium, effectively inhibits viral and host cell membrane fusion. This discovery offers a potential broad-spectrum antiviral agent against infections like influenza and coronavirus.
Area of Science:
- Virology
- Structural Biology
- Biochemistry
Background:
- Enveloped virus entry necessitates viral and host cell membrane fusion.
- Fusion inhibitors represent a promising strategy for broad-spectrum antiviral therapies.
- Mycobacterium utilizes coronin 1 to inhibit phagosome-lysosome fusion, offering a biological model.
Purpose of the Study:
- To explore the structural features of coronin 1 for antiviral drug development.
- To design and synthesize a novel lipo-peptide inhibitor of membrane fusion.
- To evaluate the broad-spectrum antiviral potential of the designed lipo-peptide.
Main Methods:
- Structural analysis of coronin 1 and WD40-repeat proteins.
- Identification of a key trp-asp (WD) sequence in a distorted beta-meander motif.
- Design and synthesis of a myristoylated lipo-dipeptide (myr-WD).
- In vitro assessment of membrane fusion inhibition by myr-WD.
- In vivo testing against influenza (H1N1) and murine coronavirus.
Main Results:
- The trp-asp (WD) sequence in coronin 1 is structurally exposed.
- The synthesized myr-WD lipo-peptide effectively inhibits membrane fusion.
- myr-WD modulates interfacial order, water penetration, and surface potential.
- myr-WD demonstrated efficacy against type 1 influenza virus and murine coronavirus.
Conclusions:
- The structural insights from coronin 1 led to the development of an effective membrane fusion inhibitor.
- The myr-WD lipo-peptide shows significant potential as a broad-spectrum antiviral agent.
- This approach offers a novel strategy for combating viral infections by targeting membrane fusion.
