SARS-CoV-2 and Coronaviruses
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Direct answer
SARS-CoV-2 is an enveloped positive-sense single-stranded RNA betacoronavirus that causes COVID-19 and enters host cells mainly through the ACE2 receptor, with its spike protein primed by host TMPRSS2. Coronaviruses have the largest RNA genomes of any RNA virus, and four structural proteins (spike, envelope, membrane and nucleocapsid) build the particle. RT-PCR on respiratory specimens remains the reference diagnostic test.
What you must remember
- Classification: Coronaviridae belongs to the order Nidovirales, and SARS-CoV, MERS-CoV and SARS-CoV-2 are betacoronaviruses, whereas 229E and NL63 are alphacoronaviruses.
- Structural proteins: The spike (S) protein gives the crown-like outline and mediates receptor binding and fusion, while envelope, membrane and nucleocapsid proteins complete the particle.
- Common cold coronaviruses: 229E, OC43, NL63 and HKU1 cause mild upper respiratory infections in humans.
- Receptors: SARS-CoV and SARS-CoV-2 use ACE2, whereas MERS-CoV uses dipeptidyl peptidase 4 (DPP4).
- MERS: First recognised in 2012 and linked to dromedary camels, it causes severe respiratory disease but spreads less efficiently than SARS-CoV-2.
- Diagnosis: RT-PCR targets genes such as E, RdRp and N on nasopharyngeal or oropharyngeal swabs, and rapid antigen tests are less sensitive.
- Variant naming: The WHO assigns Greek letters to variants of concern, such as Alpha, Delta and Omicron, and later sublineages are referred to by lineage names.
- Genomic surveillance: India's INSACOG network coordinates genome sequencing of positive samples to track variants.
Three betacoronaviruses compared
SARS-CoV, MERS-CoV and SARS-CoV-2 are the three coronaviruses that cause severe disease in humans, and exams compare them on receptor, source and spread. The table sets out these features side by side.
| Feature | SARS-CoV | MERS-CoV | SARS-CoV-2 |
|---|---|---|---|
| First recognised | 2002 | 2012 | 2019 |
| Receptor | ACE2 | DPP4 | ACE2 |
| Animal link | Bats, with civets as intermediate | Dromedary camels | Bat origin likely, intermediate unclear |
| Spread | Mainly droplets | Limited, close contact | Highly transmissible |
| Severity | High | Among the highest | Wide spectrum, mostly mild |
MERS is the most lethal of the three but spreads least efficiently, whereas SARS-CoV-2 spreads most efficiently and causes a wide range of disease. The receptor row is the fastest way to answer pairing questions, since only MERS-CoV uses DPP4.
RT-PCR confirms infection by detecting several viral genes, and positive samples are sent for sequencing so that variants can be tracked. Antigen tests are useful for rapid screening, but a negative result in a symptomatic patient does not exclude infection.
Where the exam tries to catch you
Coronavirus questions usually test the receptor pairing, the genome type and the diagnostic reference test.
- Trap: Calling SARS-CoV-2 a DNA virus or a retrovirus Correct: It is an enveloped positive-sense ssRNA betacoronavirus that replicates in the cytoplasm without reverse transcription into the host genome.
- Trap: Pairing MERS-CoV with ACE2 Correct: MERS-CoV uses DPP4, whereas SARS-CoV and SARS-CoV-2 both use ACE2.
- Trap: Relying on a rapid antigen test to exclude infection in a symptomatic patient Correct: RT-PCR remains the reference test, because antigen tests are less sensitive, especially when viral loads are low.
Frequently asked questions
Which receptor does SARS-CoV-2 use to enter human cells?
SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as its main receptor, and host proteases such as TMPRSS2 prime its spike protein for fusion. SARS-CoV also uses ACE2, which is why the two viruses are compared so often.
Which coronavirus uses dipeptidyl peptidase 4 as its receptor?
MERS-CoV uses dipeptidyl peptidase 4 (DPP4) as its receptor, which is distinct from the ACE2 used by SARS-CoV and SARS-CoV-2. MERS was first recognised in 2012 and is linked to dromedary camels.
What is the reference test for diagnosing SARS-CoV-2 infection?
RT-PCR on nasopharyngeal or oropharyngeal swabs is the reference test for SARS-CoV-2 infection. Rapid antigen tests are quicker but less sensitive, especially when viral loads are low.
Which proteins make up the coronavirus particle?
The coronavirus particle is built from spike, envelope, membrane and nucleocapsid proteins. The spike protein gives the crown-like outline and mediates receptor binding and fusion, and it is the main target of current vaccines.
Why does the WHO give Greek letters to some SARS-CoV-2 variants?
The WHO assigns Greek letters to variants of concern, such as Alpha, Delta and Omicron, so that they are easier to discuss than technical lineage names. Later Omicron sublineages are usually referred to by their lineage names instead.