In silico Antivirus Repurposing and its Modification to Organoselenium Compounds as SARS-CoV-2 Spike Inhibitors

Area of Science:

• Computational chemistry
• Drug discovery
• Virology

Background:

• COVID-19, caused by SARS-CoV-2, is a highly infectious global pandemic.
• The SARS-CoV-2 spike glycoprotein is crucial for viral entry by binding to ACE-2 receptors.
• Inhibiting spike glycoprotein function presents a therapeutic strategy for COVID-19.

Purpose of the Study:

• To repurpose existing antiviral drugs into novel SARS-CoV-2 inhibitors.
• To design and synthesize organoselenium compounds based on promising drug scaffolds.
• To computationally evaluate the efficacy of these compounds against the SARS-CoV-2 spike glycoprotein.

Main Methods:

• In silico molecular docking (rigid and flexible) using MOE 2014.09.
• Quantitative Structure-Activity Relationship (QSAR) guided modification of lead compounds.
• Analysis of binding energy, ADME-Tox properties, and RMSD values for ligand selection.

Main Results:

• Initial docking identified top unmodified ligands (Ombitasvir, Elbasvir, Ledipasvir) with high binding affinities.
• QSAR-based modifications yielded 96 new organoselenium compounds.
• The best modified ligands (ModL1, ModL2, ModL3) demonstrated significant binding energies and favorable RMSD values.

Conclusions:

• Repurposed and modified organoselenium compounds show potential as SARS-CoV-2 antivirals.
• Computational analysis successfully identified lead candidates targeting the spike glycoprotein.
• Further experimental validation is warranted for these promising therapeutic agents.