Structural Proteins in Severe Acute Respiratory Syndrome Coronavirus-2

Abstract

What began with a sign of pneumonia-related respiratory disorders in China has now become a pandemic named by WHO as Covid-19 known to be caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The SARS-CoV-2 are newly emerged β coronaviruses belonging to the Coronaviridae family. SARS-CoV-2 has a positive viral RNA genome expressing open reading frames that code for structural and non-structural proteins. The structural proteins include spike (S), nucleocapsid (N), membrane (M), and envelope (E) proteins. The S1 subunit of S protein facilitates ACE2 mediated virus attachment while S2 subunit promotes membrane fusion. The presence of glutamine, asparagine, leucine, phenylalanine and serine amino acids in SARS-CoV-2 enhances ACE2 binding. The N protein is composed of a serine-rich linker region sandwiched between N Terminal Domain (NTD) and C Terminal Domain (CTD). These terminals play a role in viral entry and its processing post entry. The NTD forms orthorhombic crystals and binds to the viral genome. The linker region contains phosphorylation sites that regulate its functioning. The CTD promotes nucleocapsid formation. The E protein contains a NTD, hydrophobic domain and CTD which form viroporins needed for viral assembly. The M protein possesses hydrophilic C terminal and amphipathic N terminal. Its long-form promotes spike incorporations and the interaction with E facilitates virion production. As each protein is essential in viral functioning, this review describes the insights of SARS-CoV-2 structural proteins that would help in developing therapeutic strategies by targeting each protein to curb the rapidly growing pandemic.

Keywords: COVID-19; Nucleocapsid; Pandemic; SARS-CoV-2; Structural protein.

Graphical abstract

Figure 1

Family of Coronaviruses. Coronaviruses are divided into four genera namely α coronavirus, β coronavirus, γ coronavirus, and δ coronavirus. The α coronavirus is further divided into sub groups a and b, while the β coronavirus is divided into a, b, c, and d (7). TGEV-Transmittable Gastroenteritis Virus TGEV, PRCV-Porcine Respiratory Coronavirus, CDPHE-Colorado Department of Public Health and Environment, MHV-Murine Hepatitis Virus, PHEV-Porcine Hemagglutinating Encephalomyelitis Virus, MERS-CoV-Middle East Respiratory Syndrome Coronavirus, SARS-CoV-Severe Acute Respiratory Syndrome Coronavirus, WSFMP-Wuhan Seafood Market Pneumonia.

Figure 2

Newly Identified Family of SARS-CoV-2 (WSFMP_Wuhan-Hu-1 is used as a reference). WSFMP- Wuhan Seafood Market Pneumonia, 2019-nCoV- 2019-novel Coronavirus.

Figure 3

Genomic sequence of SARS-CoV-2. ORF–Open Reading Frame, UTR-Untranslated region, S-Spike protein, M-Membrane protein, E-Envelope protein, N-Nucleocapsid protein.

Figure 4

Schematic representation of SARS-CoV-2 structure.

Figure 5

Types of SARS-CoV-2 genotypes.

Figure 6

A. Schematic Illustration of the Structure of Spike Protein. B. Genomic Sequence of Spike Protein (28). SP-Signal Peptide, NTD-N terminal Domain, RBM-Receptor Binding Motif, RBD-Receptor Binding Domain, FP-Fusion Peptide, HR1-Heptat Repeat 1, HR2-Heptad Repeat 2, TM-Transmembrane Domain, CP-Cytoplasm Domain.

Figure 7

Genomic sequence of SARS-CoV-2 N protein (36).