Molecular characterization and amino acid homology of nucleocapsid (N) Protein in SARS-CoV-1, SARS-CoV-2, MERS-CoV, and bat coronavirus

Abstract

Coronavirus disease – 2019 (COVID-19) pandemic, due to severe acute respiratory syndrome–coronavirus-2 (SARS-CoV-2), is posing a severe bio threat to the entire world. Nucleocapsids of SARS-CoV-2 and the related viruses were studied for gene and amino acid sequence homologies. In this study, we established similarities and differences in nucleocapsids in SARS-CoV-2, severe acute respiratory syndrome – coronavirus-1 (SARS-CoV-1), bat coronavirus (bat-CoV) and Middle East respiratory syndrome - coronavirus (MERS-CoV). We conducted a detailed analysis of the nucleocapsid protein amino acid and gene sequence encoding it, found in various coronavirus strains. After thoroughly screening the different nucleocapsids, we observed a close molecular homology between SARS-CoV-1 and SARS-CoV-2. More than 95% sequence similarity was observed between the two SARS-CoV strains. Bat-CoV and SARS-CoV-2 showed 92% sequence similarity. MERS-CoV and SARS-CoV-2 nucleocapsid analysis indicated only 65% identity. Molecular characterization of nucleocapsids from various coronaviruses revealed that SARS-CoV 2 is more related to SARS-CoV 1 and bat-CoV. SARS-CoV 2 exhibited less resemblance with MERS-CoV. SARS-CoV 2 showed less similarity to MERS-CoV. Thus, either SARS-CoV-1 or bat-CoV may be the source of SARS-CoV-2 evolution. Moreover, the existing differences in nucleocapsid molecular structures in SARS-CoV-2 make this virus more virulent and highly infectious, which means that the non-identical SARS-CoV-2 genes (which are absent in SARS-CoV-1 and bat-CoV) are responsible for COVID-19 severity. We observed that SARS-CoV-2 nucleocapsid from different locations varied in amino acid sequences. This revealed that there are many SARS-CoV-2 subtypes/subsets currently circulating globally. This study will help to develop antiviral vaccine and drugs, study viral replication and immunopathogenesis, and synthesize monoclonal antibodies that can be used for precise COVID-19 diagnosis, without false-positive/false-negative results.