Coronaviruses (CoVs) are a community of Nidovirales viruses that includes the Coronaviridae, Arteriviridae, Mesoniviridae, and Roniviridae families. In the genus Coronaviridae, the Coronavirinae is one of two subfamilies, the other being the Torovirinae. The Coronavirinae family is further divided into four genera: alpha, beta, gamma, and delta coronaviruses.
Both viruses belong to the Nidovirales order and are enveloped, non-segmented positive-sense RNA viruses. These all have exceptionally broad RNA viral genomes, with some viruses producing the world’s largest RNA genomes, up to 33.5 kilobase (kb) genomes. Coronaviruses (CoVs) are diseases that affect humans and animals indiscriminately.The respiratory, urinary, and hepatic systems, and even the central nervous system, may all be affected. The 2002/2003 SARS and 2012 Middle East respiratory syndrome (MERS) epidemics demonstrated the possibility of newly-emerging CoVs being transmitted from animal to human and human to human.
2019nCoV or COVID-19 is a novel coronavirus that emerged suddenly in Wuhan, China, with an epidemic of uncommon viral pneumonia and later a pandemic epidemic. COVID-19 is classified as a Betacoronavirus based on its phylogenetic relationships and genomic architecture. COVID19’s sequences are nearly identical to those of SARS-related coronaviruses (SARSr-CoV), and the virus utilises ACE2 as the SARS-CoV entrance receptor. The Coronavirus Research Group of the International Committee on Virus Taxonomy named SARS-CoV-2 after such linkages between SARS-CoV-2 and the virus that caused the SARS outbreak (SARS-CoVs).
Coronavirus structure and life cycle
The virus particle is 60 ~ 100 nm in diameter and tends to be circular or oval (Duan et al., 2020). Coronaviruses have the biggest genomes (up to 32 kb) of all recognized RNA viruses, with amount of G+C varying from 32% to 43%. There are variable numbers of small ORFs between the separate retained genes (ORF1ab, pulse, shell, membrane and nucleocapsid) and, downstream to the nucleocapsid gene in various coronavirus lineages. The viral genome includes distinctive characteristics, including a special portion of the N-terminal inside the protein bolt. In both coronaviruses, genes for the main structural proteins exist in the 5′ to 3′ order such as S, E, M and N.
A standard CoV has a total of six ORFs in its genome. Except for Gammacoronavirus which nsp1 lakes, the first ORFs (ORF1a / b), around two-thirds of the total length of the genome, encode 16 nsps (nsp1‐16). ORF1a and ORF1b comprise a frameshift through which two polypeptides are produced: pp1a and pp1ab. Such polypeptides are translated into 16 nsps by virally encoded chymotrypsin-like protease (3CLpro) or principal protease (Mpro) and one or two papain-like protease. Both the basic proteins and accessory proteins are derived from CoV sgRNAs. ORFs 10 and 11 located in the one-third of a genome near the 3′‐terminus comprise four main structural protectins including spike (S), membrane (M), envelope(E) and nuclecapsid (N) proteins. In addition, different CoVs encode unique structural and accessory proteins including HE, 3a / b proteins and 4a / b proteins in addition to these four main structural proteins. Such mature proteins hold many primary roles in the preservation and transcription of the genomes (Mousavizadeh & Ghasemi 2020).
Sars-CoV-2 (COVID-19) attaches by its spike and permits COVID-19 to join and infiltrate cells via ACE2 (angiotensin-converting enzyme 2). The spike protein should be activated by a protease enzyme, if the virus is to complete its entrance into the cell following this initial phase. Similar to SARS-CoV, the trans-Membrane Serine Protease 2 (TMPRSS2) protease is used by SARS-CoV-2 (COVID-19) to complete this cycle. The activation of TMPRSS2 as a protease is necessary to bind the virus receptor (spike protein) to its cell ligand (ACE 2).
The virus reaches the cells and then release the viral RNA genome into the cytoplasm and is transmitted as a result of which the viral genome starts replicating in two polyproteins and structural proteins. In a membrane in the endoplasmic reticulum (Golgi) the freshly formed envelope glycoproteins are incorporated and the nucleocapsid is made up from a genomic RNA mixture with the nucleocapsid protein. In the endoplasmic Golgi intermediate compartment (ERGIC), viral particles then germinate. Finally, the viral particle vesicles combine to split the viral from the plasma membrane.
A variety of non-structural Proteins including RNA-dependent RNA polymerase (RdRp) are also encoded. When the virus enters the host cells, the viral genome is released as a single, positive RNA, which is then transformed into viral polyproteins by means of the host cell protein translation system. SARS-CoV and the MERS-CoV will induce the formation, then replicating, of the double-membrane vesicles deficient in PRRs and thus prevent the identification by host of their dsRNA.
Non-Structural protiens of corona viruses and their function:
Humoral and cellular immunity
More work on the cellular immunity of coronavirus is done in conjunction with humoral responses. Around one week after initiation of symptoms, SARS-CoV-2 can be observed with adaptive immune responses (both T and B cells). Similar to viruses and/or virus-infected cells, these adaptive immune responses are very strong. T-cells perform two essential functions. CD8+T-cells actively invade and destroy virus-infected cells, while CD4+T-cells control primate B-cells and CD8+T-cells, which generate cytokine to attract immune cells.
In patients at the acute stage of SARS-CoV infection, T cell reactions are seriously hampered. In these patients, weakened T cell activation leads to an increase in viral load duration. The altered dendritic (DC) cell maturation and lymphoid organ migration is one explanation for this weaking T cell response, because dendritic cells are essential for the activation of T cells. MERS-CoV infection has triggered a small rise in the amount of CD8 cells, however the activation profiles of the CD4 + T cells remain unstable in patients. Although this reaction has been impaired, convalescent patients develop memory T cells that are specific to coronavirus. They can be found in patients for up to 2 years after recovery. This pro-inflammatory profile will cause the infection worse.
The prevalent immunopathologic syndrome of SARS-CoV-2, SARS CoV and MERS-CoV infections and mortality is Acute Respiratory Distress Syndrome (ARDS). One of the key pathways for ARDS is the cytokine storm, the deadly unregulated systemic inflammatory reaction arising from the release of vast amounts of pro-inflammatory cytokines (IFN-a, IFN-g, IL-1b, IL-6, IL-12, IL-18, IL-33, TNF-a, TGFb, etc.) and chemokines (CCL2, CCL3, CCL5, CXCL8, CXCL9, CXCL10, etc.) from immune effector cells in SARS-CoV infection(Li et al., 2020).
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