Gene of the month: the 2019-nCoV/SARS-CoV-2 novel coronavirus spike protein

Abstract

<jats:p>The year 2020 has seen a major and sustained outbreak of a novel betacoronavirus (severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2) infection that causes fever, severe respiratory illness and pneumonia, a disease called COVID-19. At the time of writing, the death toll was greater than 120 000 worldwide with more than 2 million documented infections. The genome of the CoV encodes a number of structural proteins that facilitate cellular entry and assembly of virions, of which the spike protein S appears to be critical for cellular entry. The spike protein guides the virus to attach to the host cell. The spike protein contains a receptor-binding domain (RBD), a fusion domain and a transmembrane domain. The RBD of spike protein S binds to Angiotensin Converting Enzyme 2 (ACE2) to initiate cellular entry. The spike protein of SARS-CoV-2 shows more than 90% amino acid similarity to the pangolin and bat CoVs and these also use ACE2 as a receptor. Binding of the spike protein to ACE2 exposes the cleavage sites to cellular proteases. Cleavage of the spike protein by transmembrane protease serine 2 and other cellular proteases initiates fusion and endocytosis. The spike protein contains an addition furin cleavage site that may allow it to be ‘preactivated’ and highly infectious after replication. The fundamental role of the spike protein in infectivity suggests that it is an important target for vaccine development, blocking therapy with antibodies and diagnostic antigen-based tests. This review briefly outlines the structure and function of the 2019 novel CoV/SARS-CoV-2 spike protein S.</jats:p>

Epitope-resolved profiling of the SARS-CoV-2 antibody response identifies cross-reactivity with an endemic human CoV

“…A second rationale for generating epitope-resolved views is that antibody recognition of different protein regions can have divergent functional consequences, including neutralization potential. For coronaviruses, antibodies binding the surface-exposed, receptor-binding S protein exhibit the greatest neutralizing potential (Du et al, 2009;Pillay, 2020), but these antibodies can recognize a wide variety of epitopes within the protein, each with the potential for different functional consequences. This likely accounts for the imperfect correlation between the titers of S-binding antibodies and viral neutralization activity across individuals (Robbiani et al, 2020).…”

Identification of potential biomarkers and inhibitors for SARS-CoV-2 infection

“…And based on our KEGG studies, we found the COVID-19 patients were In addition, the infection of COVID-19 is also associated with the cellular macromolecule catabolic process including the regulation of RNA metabolic process and the proteolysis involved in cellular protein catabolic process based on our GO analysis. Entry of the SARS-CoV-2 is mainly dependent on proteolytic activation of the spike protein 18 . During the process of viral infection, the spike protein is cleaved into the S1 and S2 subunits and the S2 subunit is released 19 .…”

Clinical outcomes of patients with COVID-19 admitted for respiratory support to the intensive care units in Russia

“…Следует отметить, что при анализе частоты ИБС мы учитывали только больных с достоверным диагнозом коронарной болезни сердца, установленным на основании инфаркта миокарда и/или вмешательств на коронарных артериях в анамнезе. Связь между сердечно-сосудистыми заболеваниями и риском развития или более тяжелого течения COVID-19 может опосредоваться ренин-ангиотензиновой системой, так как ангиотензинпревращающий фермент 2 (АПФ2) является рецептором SARS-CoV-2 на поверхности альвеолоцитов и клеток других тканей [35]. Мы сравнивали клинические исходы только у больных, находившихся в ОРИТ.…”