<p><b>Background and Objectives:</b> By the end of 2019, a novel human coronavirus outbreak started in Wuhan and spread to the world becoming a global pandemic, patients were diagnosed with severe respiratory syndrome. Studies have shown that SARS-CoV2 interact with angiotensin-converting enzyme 2 (ACE2), its host cell receptor, by its Spike Glycoprotein. The aim of this study is to prevent this interaction by inhibiting Spike glycoprotein.<b> Materials and Methods:</b> The interaction of the

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... ike Glycoprotein of SARS-COV-2 extracted from protein data bank (PDB Code: 6VSB and 6LZG) with 10 different ferrocene derivatives ligands were investigated by performing docking studies using Autodock Tools 4.2. software. <b>Results:</b> The obtained results showed that N-ferrocenyl-methyl-3-nitroaniline was the best inhibitor ligand interacted with both proteins of coronavirus with the free binding energy equal to -5.38 and -6.65 Kcal/mol for 6VSB and 6LZG respectively with binding constant values equal to 8.7 × 10³ and 72.72× 10³respectively. Calculations revealed that the dominated mode of interaction for all the studied ligands with COVID-19 was the electrostatic mode via at least one H-bond and more than two hydrophobic Pi-Alkyl Bonds. <b>Conclusion: </b>Generally, the results indicated the existence of strong interactions between ligands and spike glycoprotein which prevent the virus to interact to ACE2 receptors.</p>