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Peptide derivatives as inhibitors of SARS-CoV-2-S protein

Spike surface glycoprotein (S protein) is a component of coronavirus virion particle and it is responsible for viral recognition of Angiotensin Converting Enzyme 2 (ACE2). S protein binds with to human ACE2 and uses it as an entry receptor to invade target cells. S1 subunit is responsible for binding to the host cell receptor, while S2 subunit for the fusion of the viral and cellular membranes. SARS-CoV infection could be blocked by inhibitors that bind to the RBD and induced conformational changes in S glycoprotein and prevents binding to the ACE2. Peptide-type compounds were found to have promising activity against SARCoV. Consequently, these molecules attracted the attention of researchers to prepare and test their more derivatives. In order to screen the abilities for binding to the SARS-CoV-2 spike glycoprotein (S protein) of previously proven peptide-type SARS-CoV 3CL protease inhibitors, we performed the molecular docking study. The three dimensional structure of the SARS-CoV-2 spike glycoprotein in complex with N-acetyl-D- glucosamine as ligand (NAG) (pdb: 6VSB) was downloaded from the Protein Data Bank. Molecular docking was performed on 62 optimized structures of compounds (1-62) and antiviral drug Remdesivir. The highest binding affinity towards S protein has compound 21 (E = -127.2 kcal mol-1). Compound 21 is in conformation that forms a cluster of H-atom acceptor (O and N atoms), which allows stronger biding to S1 subdomain. Antiviral drug Remdesivir demonstrated low binding affinity to the S protein.

SARS-CoV-2 ; spike glycoprotein ; peptide-type compounds ; molecular docking

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