ORF۸: Promising Target Protein for COVID-۱۹ Treatment

Backgrounds: Recent pernicious COVID-۱۹ pandemic is caused by Severe Acute RespiratorySyndrome Coronavirus-۲ (SARS-CoV-۲). SARS-CoV-۲ accessory proteins are known to playkey roles in host immune regulation and immune evasion. Amidst them, Open-Reading Frame ۸(ORF۸) as a unique protein, has some prominent roles in disease severity, most striking of themare interaction with Major Histocompatibility Complex-۱ (MHC-۱) and its down-regulation,Interleukin-۶ production and, the antagonistic effect on Interferon Regulatory TranscriptionFactor-۳ (IRF-۳). In this study, we explore the molecular features of ORF۸ to find the potentialhotspot binding sites of the protein for proposing appropriate inhibitors, especially among thenatural products (NPs).Materials and Methods: The X-ray ۳D structure of ORF۸ was obtained from the Protein DataBank )PDB). The ligand-binding sites were predicted using sequence features and the I-TASSERserver (https://zhanggroup.org//I-TASSER/). The native ligands were then predicted using the ITASSERserver. Potential phytochemical and bacterial NP inhibitors were obtained from thePubChem server (https://pubchem.ncbi.nlm.nih.gov/). All molecular visualization was performedusing PyMOL ۲.۵.۱ and Chembiooffice ۱۴.۰ softwares. Molecular docking was executed usingAutodock vina ۱.۱.۲ software.Results: The proposed hotspots included the ۷۳YIDI۷۶ motif in addition to R۴۸, E۵۹, L۸۴, E۹۲,K۹۴ and, R۱۰۱ residues. Through molecular docking it is found that NPs included sesquiterpenelactone phytochemical, Artemisinin, macrocyclic bacterial metabolite, Ivermectin and, thelactose derivative DEG-۱۶۸ small molecule as potential inhibitors.Conclusion: ORF۸ is a key target for inhibition by Artemisinin, Ivermectin, and lactoside DEG-۱۶۸.

کلیدواژه ها:

COVID-۱۹ ، ORF۸ ، Molecular docking ، Artemisinin ، Ivermectin