Coronaviruses: Genes and Proteins

Coronavirus Structure and Replication Process

• Nucleocapsids in coronaviruses are formed from viral N-protein bound to viral RNA in a helical fashion, resembling '-' strand RNA viruses, and some may have a spherical core structure formed via the M-protein.
• Corona virions contain multiple envelope proteins: spike (S), membrane (M), envelope (E), nucleocapsid (N), and in some cases, HE (hemagglutinin esterase) protein.
• Spike protein, a major surface transmembrane glycoprotein, is responsible for viral entry and tropism, and it generally forms trimers.
• Spike proteins bind to a variety of cellular receptors, with different coronaviruses utilizing different receptors for entry.
• The replicase gene (gene 1) in coronaviruses is composed of ORF1a and ORF1b, which are translated into polyproteins that are processed by viral proteinases.
• RNA helicase and nucleoside triphosphatase activities, as well as RNA exonuclease with proofreading activity, are involved in coronavirus replication.
• Membrane association of viral RNA synthesis is common among '+ strand RNA viruses of eukaryotes, and replication complexes are the site of viral RNA synthesis.
• Coronavirus-induced membrane alterations involve the rearrangement of subcellular architecture, with replication complexes commonly observed on double membrane vesicles.
• Genome replication proceeds via a full-length negative-strand intermediate, used to direct synthesis of full-length '+' strand genomes, and subgenomic mRNAs are transcribed from subgenomic negative-strand mRNA templates.
• Subgenomic mRNAs contain overlapping sequences on their 3' end and are transcribed from subgenomic negative-strand mRNA templates made by discontinuous transcription.
• Rearrangement of subcellular architecture and membrane association of viral RNA synthesis are observed in coronavirus-infected cells, involving double membrane vesicles and convoluted membranes.
• The replicase gene in coronaviruses is composed of ORF1a and ORF1b, which are translated into polyproteins that are processed by viral proteinases.

Coronavirus Structure and Replication Process

• Nucleocapsids in coronaviruses are formed from viral N-protein bound to viral RNA in a helical fashion, resembling '-' strand RNA viruses, and some may have a spherical core structure formed via the M-protein.
• Corona virions contain multiple envelope proteins: spike (S), membrane (M), envelope (E), nucleocapsid (N), and in some cases, HE (hemagglutinin esterase) protein.
• Spike protein, a major surface transmembrane glycoprotein, is responsible for viral entry and tropism, and it generally forms trimers.
• Spike proteins bind to a variety of cellular receptors, with different coronaviruses utilizing different receptors for entry.
• The replicase gene (gene 1) in coronaviruses is composed of ORF1a and ORF1b, which are translated into polyproteins that are processed by viral proteinases.
• RNA helicase and nucleoside triphosphatase activities, as well as RNA exonuclease with proofreading activity, are involved in coronavirus replication.
• Membrane association of viral RNA synthesis is common among '+ strand RNA viruses of eukaryotes, and replication complexes are the site of viral RNA synthesis.
• Coronavirus-induced membrane alterations involve the rearrangement of subcellular architecture, with replication complexes commonly observed on double membrane vesicles.
• Genome replication proceeds via a full-length negative-strand intermediate, used to direct synthesis of full-length '+' strand genomes, and subgenomic mRNAs are transcribed from subgenomic negative-strand mRNA templates.
• Subgenomic mRNAs contain overlapping sequences on their 3' end and are transcribed from subgenomic negative-strand mRNA templates made by discontinuous transcription.
• Rearrangement of subcellular architecture and membrane association of viral RNA synthesis are observed in coronavirus-infected cells, involving double membrane vesicles and convoluted membranes.
• The replicase gene in coronaviruses is composed of ORF1a and ORF1b, which are translated into polyproteins that are processed by viral proteinases.

Coronavirus Structure and Replication Process

• Nucleocapsids in coronaviruses are formed from viral N-protein bound to viral RNA in a helical fashion, resembling '-' strand RNA viruses, and some may have a spherical core structure formed via the M-protein.
• Corona virions contain multiple envelope proteins: spike (S), membrane (M), envelope (E), nucleocapsid (N), and in some cases, HE (hemagglutinin esterase) protein.
• Spike protein, a major surface transmembrane glycoprotein, is responsible for viral entry and tropism, and it generally forms trimers.
• Spike proteins bind to a variety of cellular receptors, with different coronaviruses utilizing different receptors for entry.
• The replicase gene (gene 1) in coronaviruses is composed of ORF1a and ORF1b, which are translated into polyproteins that are processed by viral proteinases.
• RNA helicase and nucleoside triphosphatase activities, as well as RNA exonuclease with proofreading activity, are involved in coronavirus replication.
• Membrane association of viral RNA synthesis is common among '+ strand RNA viruses of eukaryotes, and replication complexes are the site of viral RNA synthesis.
• Coronavirus-induced membrane alterations involve the rearrangement of subcellular architecture, with replication complexes commonly observed on double membrane vesicles.
• Genome replication proceeds via a full-length negative-strand intermediate, used to direct synthesis of full-length '+' strand genomes, and subgenomic mRNAs are transcribed from subgenomic negative-strand mRNA templates.
• Subgenomic mRNAs contain overlapping sequences on their 3' end and are transcribed from subgenomic negative-strand mRNA templates made by discontinuous transcription.
• Rearrangement of subcellular architecture and membrane association of viral RNA synthesis are observed in coronavirus-infected cells, involving double membrane vesicles and convoluted membranes.
• The replicase gene in coronaviruses is composed of ORF1a and ORF1b, which are translated into polyproteins that are processed by viral proteinases.

Coronavirus Structure and Replication Process

• Nucleocapsids in coronaviruses are formed from viral N-protein bound to viral RNA in a helical fashion, resembling '-' strand RNA viruses, and some may have a spherical core structure formed via the M-protein.
• Corona virions contain multiple envelope proteins: spike (S), membrane (M), envelope (E), nucleocapsid (N), and in some cases, HE (hemagglutinin esterase) protein.
• Spike protein, a major surface transmembrane glycoprotein, is responsible for viral entry and tropism, and it generally forms trimers.
• Spike proteins bind to a variety of cellular receptors, with different coronaviruses utilizing different receptors for entry.
• The replicase gene (gene 1) in coronaviruses is composed of ORF1a and ORF1b, which are translated into polyproteins that are processed by viral proteinases.
• RNA helicase and nucleoside triphosphatase activities, as well as RNA exonuclease with proofreading activity, are involved in coronavirus replication.
• Membrane association of viral RNA synthesis is common among '+ strand RNA viruses of eukaryotes, and replication complexes are the site of viral RNA synthesis.
• Coronavirus-induced membrane alterations involve the rearrangement of subcellular architecture, with replication complexes commonly observed on double membrane vesicles.
• Genome replication proceeds via a full-length negative-strand intermediate, used to direct synthesis of full-length '+' strand genomes, and subgenomic mRNAs are transcribed from subgenomic negative-strand mRNA templates.
• Subgenomic mRNAs contain overlapping sequences on their 3' end and are transcribed from subgenomic negative-strand mRNA templates made by discontinuous transcription.
• Rearrangement of subcellular architecture and membrane association of viral RNA synthesis are observed in coronavirus-infected cells, involving double membrane vesicles and convoluted membranes.
• The replicase gene in coronaviruses is composed of ORF1a and ORF1b, which are translated into polyproteins that are processed by viral proteinases.

Viral Translation and Replication Mechanisms

• Poly(A) tail is encoded by the genome, but usually added by poly(A) polymerases
• 5’ NCR contains an internal ribosome entry site (IRES) allowing translation initiation without a 5’ cap
• IRES elements contain a pyrimidine rich track near AUG to imitate translation at the correct spot
• Virions bind to cellular receptors via ‘canyons’ or loop regions on their surface
• Picornavirus infection causes proteolytic cleavage of eIF-4G, abolishing cap-dependent translation
• Picornavirus proteins are made as a single precursor polyprotein that is autocatalytically cleaved
• Viral RNA is replicated after protein synthesis, involving a multi-protein complex bound to cellular vesicles
• Entry of poliovirus RNA into the cytoplasm involves major rearrangement, forming a channel in the cell membrane
• Virion assembly involves cleavage of VP0 to VP2 plus VP4, assembling into protomers and provirion
• Picornavirus infection inhibits host cell functions, inducing cytoplasmic vesicles and altering intracellular transport pathways
• Flavivirus virion contains an envelope and envelope proteins are arranged with icosahedral symmetry
• Flavivirus genome organization most resembles that of Picornaviruses, translated into a single, long polyprotein that undergoes proteolytic processing

Test your knowledge on the genetic makeup and protein synthesis of coronaviruses, specifically focusing on their structure and non-structural proteins (nsp) encoded in the final 1/3rd of the genome. Explore topics such as COVID-19 genome, viral protein synthesis, and genome replication.