ORF۸: Promising Target Protein for COVID-۱۹ Treatment

  • سال انتشار: 1400
  • محل انتشار: کنفرانس بین المللی ژنتیک و ژنومیکس انسانی
  • کد COI اختصاصی: CHGGE01_274
  • زبان مقاله: انگلیسی
  • تعداد مشاهده: 112
دانلود فایل این مقاله

نویسندگان

Mostafa Bagheri Far

Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran

Mohammad Yaghoubi Avini

Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran

Seyed Massoud Hosseini

Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran

Maryam Azimzadeh Irani

Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran

چکیده

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

اطلاعات بیشتر در مورد COI

COI مخفف عبارت CIVILICA Object Identifier به معنی شناسه سیویلیکا برای اسناد است. COI کدی است که مطابق محل انتشار، به مقالات کنفرانسها و ژورنالهای داخل کشور به هنگام نمایه سازی بر روی پایگاه استنادی سیویلیکا اختصاص می یابد.

کد COI به مفهوم کد ملی اسناد نمایه شده در سیویلیکا است و کدی یکتا و ثابت است و به همین دلیل همواره قابلیت استناد و پیگیری دارد.