B6: coronavirus Flashcards
What is the taxonomy of coronaviruses?
Order :Nidovirales,
Family: Coronaviridae,
Subfamily: Coronavirinae.
What are the four genera within the Coronavirinae subfamily?
Alphacoronavirus, Betacoronavirus, Deltacoronavirus, and Gammacoronavirus.
Which coronaviruses commonly cause a mild respiratory condition (the common cold)?
Alphacoronaviruses (229E and NL63) and Betacoronaviruses (OC43 and HKU1).
Which “novel” coronaviruses have emerged since 2003, and what diseases do they cause?
SARS-CoV (2003 – SARS), MERS-CoV (2012 – MERS), and SARS-CoV-2 (2019 – Covid-19); all are Betacoronaviruses causing severe respiratory diseases.
What type of genome do coronaviruses have?
A single-stranded, positive-sense RNA genome (27–33 kb) with a 5’ cap and 3’ polyA tail.
What is the basic structure of a coronavirus virion?
An enveloped virus with surface proteins, and an internal nucleocapsid (ribonucleoprotein complex, RNP) that houses the RNA genome.
What is the role of the Spike (S) protein?
It binds to the host cellular receptor (e.g., ACE2) and is the major immunogenic target for vaccines.
What roles do the M and E proteins play?
M protein is important for virion assembly; E protein is needed for efficient viral release and acts as a viroporin.
What is the function of the N protein?
It binds to and protects the RNA genome, forming the RNP complex.
What are the key steps in coronavirus entry into a host cell?
Receptor binding, endocytosis/membrane fusion, and delivery of the RNP into the cytosol.
Describe the structure of the SARS-CoV-2 Spike protein.
A large trimer (~600 kDa total), type I fusion protein with an S1 domain that binds the receptor and an S2 domain with a fusion peptide and transmembrane domain.
Which receptors do different human coronaviruses use?
HCoV-229E binds APN;
HCoV-NL63, SARS-CoV, SARS-CoV-2 bind ACE2;
HCoV-OC43 and HKU1 bind sialic acid derivatives
MERS-CoV binds DPP4.
What proteases are involved in SARS-CoV-2 spike activation?
TMPRSS2 at the plasma membrane and Cathepsin L in the endosome, which cleave and trigger conformational changes for fusion.
What happens immediately after fusion in coronavirus infection?
The RNP enters the cytosol, the genome uncoats, and acts as an early mRNA (capped and polyadenylated) for protein translation.
How does the coronavirus genome direct early protein synthesis?
The genome functions as mRNA to produce two large polyproteins (pp1a and pp1ab via ribosomal frameshift).
What is the significance of polyprotein cleavage in coronavirus replication?
Cleavage produces multiple functional non-structural proteins, including viral proteases, RdRp, helicase, and capping enzymes.
Where does coronavirus genome replication occur?
Within perinuclear double-membrane vesicles, which serve as replication factories.
What are nested subgenomic mRNAs and why are they produced?
They are a set of 3’-coterminal mRNAs, all sharing the 5’ leader sequence, used to express the structural and accessory proteins that are not translated from the genomic RNA.
How are the nested subgenomic mRNAs produced?
Via a template-switching mechanism involving Transcription Regulatory Sequences (TRS-L in the leader and TRS-B before each ORF).
What features do coronavirus subgenomic mRNAs share?
They are capped, polyadenylated, and serve as templates for the translation of “late” proteins like the Spike protein.
Where does coronavirus assembly occur?
In the ER–Golgi Intermediate Compartment (ERGIC).
How does the N protein contribute to viral assembly?
It encapsidates the RNA genome and forms the RNP complex that is recruited to the ERGIC.
What is the role of the M protein during assembly?
It interacts with N, S, and E proteins to coordinate assembly and recruit RNPs to the budding site.
What function does the E protein serve in the viral lifecycle?
It functions as a viroporin, helps induce membrane curvature, and is critical for efficient viral budding.
How are new coronavirus virions released from the cell?
Through exocytosis after assembly in the ERGIC.
Name some key SARS-CoV-2 variants of concern and their origin.
Ancestral (Wuhan), Alpha (UK), Beta (South Africa), Delta (India), Gamma (Brazil), Omicron (South Africa).
What are notable features of the Omicron variant?
: It is highly transmissible, has significant vaccine escape, and generally causes less severe disease, though high transmission can still lead to hospitalizations.
What is the Regeneron treatment for COVID-19?
A combination of monoclonal antibodies casirivimab (REGN10933) and imdevimab (REGN10987) targeting the spike protein.
What are some antiviral treatments used for SARS-CoV-2?
Remdesivir (RNA polymerase inhibitor) and Nirmatrelvir/ritonavir (viral protease inhibitors).
Which immunomodulatory drugs are used to treat COVID-19 and what are their targets?
Tocilizumab (blocks IL-6 receptor) and Baricitinib (inhibits JAK1/JAK2), both reducing inflammation.
