Coronavirus - general intro

Cov-2 intro

Type of Coronavirus: betacoronavirus lineage B

(pmid: 25810552) Upper and lower respiratory infections caused by viruses are very common in temperate climates [1,2], and cause rhinitis, pharyngitis, sinusitis, bronchiolitis and pneumonia [3,4]. Coronaviruses are a large group of RNA viruses with single-stranded RNA genomes that cause 30% of upper and lower respiratory tract infections in humans. Some coronaviruses such as human coronavirus 229E (HCoV-229E), OC43 (HCoV-OC43), HKU1 (HCoV-HKU1) and NL63 (HCoV-NL63) are detected globally and only evoke mild symptoms in most individuals [3–17], although some individuals can have more-severe illness [18,19]. However, other human coronaviruses including the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle-East respiratory syndrome coronavirus (MERS-CoV) can elicit severe symptoms and even death [20,21].

(pmid: 25810552)

-- positive-sense, single-stranded RNA of approximately 30 kb in length

-- encoding several structural and nonstructural proteins that are required for progeny virion production in a conserved linear arrangement [27,28].

-- conserved structural proteins: the matrix (M) protein, the small envelope (E) protein, the trimeric spike (S) glycoprotein and the nucleocapsid (N) protein. Some variants have a third glycoprotein, hemagglutinin-esterase (HE), which is present in lineage A betacoronaviruses.

-- N protein is located inside the virus particle and is one of the most abundant structural proteins in CoVs. It binds to the viral RNA genome to form a virion core comprising a ribonucleoprotein (RNP) complex that assumes a long helical structure [29,30]. The RNP is important for maintaining the RNA in an ordered conformation for replication and transcription.

-- N protein plays an essential part in viral RNA synthesis [31–33].

-- N protein is involved in the regulation of cellular processes, such as gene transcription, interferon inhibition, actin reorganization, host cell cycle progression and apoptosis [34–37].

-- N protein is an important diagnostic marker and immunodominant antigen in host immune responses [38–40].

-- N could be a useful antiviral drug targets against infections caused by these viruses because they serve many crucial functions during the viral lifecycle [41–43].

Virus assembly and maturation

(Kuhn 2007 pmid: 17229691) Enveloped viruses use one of three main mechanisms of assembly and budding (reviewed in references 14 and 15). Previously published studies have suggested a process that is independent of functional N protein (26, 38, 55). Experiments on tunicamycin-treated infected cells suggests that the role of spike in the budding process is also limited. Instead, assembly and budding of mature virions appear to be largely driven by correct folding and assembly of M and E proteins. Interference with M-N protein interaction has little effect on the correct incorporation of M protein into the envelope in the early stages of assembly leading to morphologically indistinguishable virions. An even less-understood process is viral closure or the pinching-off event (17). Nonetheless, it is becoming increasingly clear from multiple independent studies that an ordered lattice formation of the RNP in the immediate vicinity of the luminal face of virion envelope is integral to coronavirus budding. In SARS, MHV, and TGEV coronaviruses, the predominant forces at play in this region are those between the C-terminal tails of the M and N proteins, with the interacting residues of the M protein coming from its C-terminal luminal domain (residues 194 to 205 in the case of SARS-CoV [12]). Since the last few residues from N-CTD (the last residue being the most important) are thought to play the main anchoring role in the N-M layer, there is increasing consensus that, within the RNP, the CTDs of individual N monomers are oriented such that their C-terminal tails point toward the envelope (45). However, both the positioning and orientation of NTD remains nontrivial because of the fibrous organization of the helical RNP and the complex curved path that a fully assembled RNP traverses within the viral lumen. Further studies on the full-length N protein and complementation studies between the NTD and CTDs of N protein are needed to understand the interplay between these two domains within the N-M layer of coronaviruses.