Currently, the world is struggling with the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Prions are proteins that possess a unique conformational conversion, with the ability to rapidly shift between multiple conformations due to residue hydrophobicity and net sequence charge, and viral prion-like proteins are known as potential regulators of viral infections. However, the prion-like domains (PrD) in the SARS-CoV-2 proteome have not been analyzed. In this in silico study, using the PLAAC algorithm, we identified the presence of prion-like domains in the SARS-CoV-2 spike protein. Compared with other viruses, a striking difference was observed in the distribution of prion-like domains in the spike protein since SARS-CoV-2 is the only coronavirus with a prion-like domain found in the receptor-binding domain of the S1 region of the spike protein. The presence and unique distribution of prion-like domains in the SARS-CoV-2 receptor-binding domains of the spike protein are particularly interesting since although the SARS-CoV-2 and SARS-CoV S proteins share the same host cell receptor, angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 demonstrates a 10- to 20-fold higher affinity for ACE2. We identified prion-like domains in the α1 helix of the ACE2 receptor that interact with the viral receptor-binding domain of SARS-CoV-2. Finally, we found substantial differences in the prion-like domain of the S1 region of the spike protein across emerging variants including Omicron (B.1.1.529). Taken together, the present findings indicate that the identified PrDs in the SARS-CoV-2 receptor-binding domain (RBD) and ACE2 region that interact with RBD play important functional roles in viral adhesion and entry.
【저자키워드】 COVID-19, SARS-CoV-2, ACE2, delta variant, variants, Omicron variant, prion-like domains, PrD, 【초록키워드】 coronavirus disease, viruses, coronavirus, pandemic, variant, ACE2 receptor, in silico, omicron, angiotensin-converting enzyme 2, viral infections, Spike protein, Protein, Receptor-binding domain, RBD, Algorithm, hydrophobicity, B.1.1.529, proteome, distribution, acute respiratory syndrome, residue, domain, sequence, conformation, host cell receptor, higher affinity, prion, SARS-CoV S protein, analyzed, caused, functional, in viral, unique, the spike protein, the receptor-binding domain, conformational, the SARS-CoV-2, α1 helix, 【제목키워드】 spike, change, affinity,