Exploring the exportin-1 inhibitors for COVID-19 and anticancer treatment

Area of Science:

• Molecular biology
• Computational chemistry
• Drug discovery

Background:

• Nuclear export protein 1 (XPO1) is vital for cellular homeostasis and nucleocytoplasmic transport.
• XPO1 regulates the export of proteins involved in immune response, tumor suppression, and cell cycle.
• XPO1 is a potential therapeutic target for viral infections and cancers.

Purpose of the Study:

• To identify novel inhibitors of the XPO1 protein using a computational approach.
• To evaluate the antiviral and anticancer potential of identified XPO1 inhibitors.

Main Methods:

• Pharmacophore-assisted virtual screening.
• Molecular docking, molecular dynamics, and solvation-based free-energy studies.
• In vitro validation against SARS-CoV-2 and cancer cell lines.

Main Results:

• Identified novel compounds with stable RMSD plots and favorable binding affinities.
• Demonstrated significant hydrogen bonding interactions in computational analyses.
• Validated compounds exhibited both antiviral (SARS-CoV-2) and anticancer activities in vitro.

Conclusions:

• Novel XPO1 inhibitors were successfully identified through a multi-step computational strategy.
• The identified compounds possess dual antiviral and anticancer potential.
• This study highlights XPO1 as a viable target for developing new therapeutics against viruses and cancers.