How does the corona-virus replicate?


Coronaviruses are very unusual, large, enveloped RNA viruses of both medical and veterinary importance. They have a genome of over 30,000 nucleotides (30 K bases) so can be called gigantic in virology sense.

They are also slightly unusual in how they replicate themselves at the molecular level. They employ some unusual strategies to accomplish a complex program of gene expression. Coronavirus replication entails ribosome frameshifting during genome translation, the synthesis of both genomic and multiple sub genomic RNA species, and the assembly of progeny virions by a pathway that is unique among enveloped RNA viruses

Coronaviruses have a two-step replication mechanism. (Many RNA virus genomes contain a single, large gene that is translated by the cellular machinery of the host to produce all viral proteins). Coronaviruses may contain up to 10 separate genes.


Most ribosomes translate the biggest one of these genes, called replicase, which by itself is twice the size of many other RNA viral whole genomes. Replicase gene produces a series of enzymes that use the rest of the genome as a template to produce a set of smaller, overlapping messenger RNA molecules, which are then translated into the so-called structural proteins -- the building blocks of new viral particles

The generation of sub genomic mRNAs involves a process of discontinuous transcription and production of nonstructural proteins that are nonessential for virus replication in cell culture but appear to confer a selective advantage in vivo (which are referred to as niche-specific proteins). At least one niche-specific protein, nonstructural protein 2 (nsp2), and one structural protein, the nucleocapsid protein (N), are involved in viral RNA synthesis.

The mechanism of coronavirus replication of MHV (mouse hepatitis virus) can be seen for example.


Summary of mouse hepatitis virus (MHV) replication: - MHV binds to the host-cell receptor CEACAM-1 through interaction of the spike (S) glycoprotein. Virus entry into the host cell can occur through fusion with the surface of the host cell, with the subsequent release of the genomic RNA into the cytoplasm. Alternatively, MHV can enter the host cell through the formation of endocytic vesicles, and genomic RNA is released into the cytoplasm following fusion with the vesicle membrane (not shown). Translation of the positive-strand genomic RNA gives rise to a large polyprotein that undergoes proteolytic processing to generate an RNA-dependent RNA polymerase. Through the action of the RNA polymerase, a full-length, antisense negative-strand template is generated. Sub genomic mRNAs are synthesized, presumably from subgenomic negative-strand templates. Translation of subgenomic mRNAs gives rise to structural viral proteins. S glycoprotein is expressed on the surface of the host cell and this might contribute to fusion with neighboring uninfected cells by binding to CEACAM-1. Virus assembly occurs within vesicles, followed by virus release by fusion of virion-containing vesicles with the plasma membrane. Released virus can infect other cells and can replicate within the parent cell through binding to CEACAM-1. E, envelope protein; ER, endoplasmic reticulum; M, membrane protein; N, nucleocapsid protein; ORF, open reading frame

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