A unique view of SARS-CoV-2 through the lens of ORF8 protein

Sk Sarif Hassan ,Bruce D Uhal,Ramesh Kandimalla,Shinjini Ghosh,Pritam Kumar Panda,Amos Lal,Pabitra Pal Choudhury,Damiano Pizzol,Guy W Dayhoff,Samendra P Sherchan,Tarek Mohamed Abd El-Aziz,Elrashdy M Redwan,Murtaza M Tambuwala,Vladimir N Uversky,Parise Adadi,Gaurav Chauhan,Murat Seyran,Debmalya Barh,Diksha Attrish,Kazuo Takayama,Gajendra Kumar Azad,Alaa A A Aljabali,Nima Rezaei,Amr El-Demerdash,Kenneth Lundström ,Adam Brufsky ,Wagner Baetas‐Da‐Cruz ,Giorgio Palù ,Ãngel Serrano‐Aroca ,Nicolás G Bazán ,António Soares ,Yogendra Kumar Mishra

doi:10.1016/j.compbiomed.2021.104380

Abstract

Immune evasion is one of the unique characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attributed to its ORF8 protein. This protein modulates the adaptive host immunity through down-regulation of MHC-1 (Major Histocompatibility Complex) molecules and innate immune responses by surpassing the host's interferon-mediated antiviral response. To understand the host's immune perspective in reference to the ORF8 protein, a comprehensive study of the ORF8 protein and mutations possessed by it have been performed. Chemical and structural properties of ORF8 proteins from different hosts, such as human, bat, and pangolin, suggest that the ORF8 of SARS-CoV-2 is much closer to ORF8 of Bat RaTG13-CoV than to that of Pangolin-CoV. Eighty-seven mutations across unique variants of ORF8 in SARS-CoV-2 can be grouped into four classes based on their predicted effects (Hussain et al., 2021) [1]. Based on the geo-locations and timescale of sample collection, a possible flow of mutations was built. Furthermore, conclusive flows of amalgamation of mutations were found upon sequence similarity analyses and consideration of the amino acid conservation phylogenies. Therefore, this study seeks to highlight the uniqueness of the rapidly evolving SARS-CoV-2 through the ORF8.

Highlights

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is a novel coronavirus whose first outbreak was reported in December 2019 in Wuhan, China, where a cluster of pneumonia cases was detected
SAR S-CoV ORF8b showed a high degree of similarity as a greater Q score represents high similarity, whereas ORF7a and ORF8a consist of less similarity with the ORF8 of SARS-CoV-2
The SARS-CoV-2 ORF8 protein contains an N-terminal hydrophobic signal peptide (1–15 aa), which is involved in the same function

Summary

Introduction

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is a novel coronavirus whose first outbreak was reported in December 2019 in Wuhan, China, where a cluster of pneumonia cases was detected. SARS-CoV-2 is an enveloped, single-stranded RNA virus of positive polarity whose genome is approximately 30 kb in length and encodes 16 non-structural proteins, four structural, and six accessory proteins [9,10,11], ORF3a, ORF6, ORF7a, ORF7b, ORF8, and ORF10 (Fig. 1A) [12,13,14,15,16]. Among these accessory proteins, SARS-CoV-2 ORF8 is a complete protein, as it is different from any other known coronavirus ORF8 and thereby can be associated with SARS-CoV-2 pathogenicity [17,18]. The SARS-CoV-2 ORF8 displays arrays of functions; inhibition of interferon 1, promotion of viral repli cation, induction of apoptosis, and modulation of the ER stress [19,20,21]

Methods

Results

Conclusion