Analyzing Monomeric and Dimeric ORF۸ Interactions with Antiviral Small Molecules

Open reading frame (ORF۸) is a SARS-CoV-۲ accessory protein with monomeric anddimeric structures [۱][۲][۳]. ORF۸ exerts multiple different functions that interfere with host immuneresponses, including downregulation of MHC class I molecules, inducing ER stress and triggeringinflammatory response through IL-۱۷ pathway [۱]. In terms of connections with human proteinnetworks, ORF۸, along with the membrane(M) protein and Nsp۷, was statistically identified as asignificant protein of SARS-CoV-۲ [۱][۴]. Therefore, studying how ORF۸ structures interact withantiviral drugs can help treat COVID-۱۹ and identify new targets for vaccines and drugs. ORF۸’s ۳Dstructures were obtained from Protein Data bank with PDB ID ۷F۵F [۲] for monomeric structure andPDB ID ۷JTL [۳] for dimeric structure. Remdesivir CID ۱۲۱۳۰۴۰۱۶, Artemisinin CID ۶۸۸۲۷ andIvermectin B۱a CID ۶۳۲۱۴۲۴ were selected as antiviral small molecules and their structures wereobtained from PubChem database [۵]. Blind molecular docking between each chosen drug with ORF۸monomeric and dimeric structures was performed using Autodock۴ [۶]. The ORF۸ amino acids thatform hydrogen bonds with Remdesivir are ASP۴۶, CYS۴۴, GLU۴۲ (monomer) and GLN۱۱۱, ALA۳(dimer); with Artemisinin is ARG۸۴, LYS۲۷ (monomer) and ARG۳۴ (dimer) and with Ivermectin B۱aare LYS۵۱, HIS۲۳, PHE۲۴, CYS۶۶, PHE ۶۹(monomer) and GLN۱۳, ARG۱۴۵ (dimer).The results indicate that small molecules binding sites are not overlapping. Furthermore, based on theORF۸ amino acids involved in hydrogen bonds with the drugs, the binding epitopes of monomeric anddimeric ORF۸ differ. This information can help develop drugs that target specific binding sites andepitopes.

کلیدواژه ها:

SARS-CoV-۲ ، ORF۸ ، Molecular Docking ، Antiviral small molecules