An introduction to SARS-CoV-2, the virus causing COVID-19

19th Nov 2020

SARS-CoV-2, the virus causing COVID-19, is a coronavirus. Many different coronaviruses are known to infect humans. They typically cause respiratory infections of varying degrees of severity. In some cases, different types of coronaviruses may lead to gastrointestinal infections. 

In the last 20 years, coronaviruses were the cause of two outbreaks, SARS-CoV in 2002 / 2003, and MERS-CoV in 2012. In 2019, another coronavirus—SARS-CoV-2, emerged in Wuhan, China. 

Timeline of coronavirus outbreaks from 2000 to 2020. 2002 was SARS-CoV. 2012 was MERS-CoV. 2019 was SARS-CoV-2. Illustration.

Figure 1. Timeline of coronavirus outbreaks over the last 20 years. 

To develop drug treatments and vaccines against SARS-CoV-2, it is essential to understand the structure and characteristics of this novel virus. 

 

The structure of SARS-CoV-2

The genome of coronaviruses is encoded by single-stranded ribonucleic acid (RNA). The RNA is surrounded by a lipid envelope, which contains a number of different proteins. This gives the coronavirus the appearance of a crown. Crown, in Latin, is corona—hence the name coronavirus.

Coronavirus highlighting envelope, RNA, proteins. Illustration.

Figure 2. Structure of a coronavirus.

 

How does SARS-CoV-2 infect human cells?

The virus uses a receptor known as an angiotensin-converting enzyme 2 (ACE2) receptor, in order to gain entry to a host cell. ACE2 receptors are highly expressed in cells of the nose, lower respiratory system, heart, kidney, gastrointestinal system, and endothelial cells in humans. Proteins present on the surface of the virus, known as S proteins or spike proteins, bind to the ACE2 receptor allowing the virus to attach and release its RNA into the cell.

Series of images. Cell with virus. Cells with virus bound to receptor. Virus fusing with cell membrane. Viral contents in cell. Illustration.

Figure 3. Infection of human cells with SARS-CoV-2, a) SARS-CoV-2 in proximity to host cell, b) SARS-CoV-2 binding to a receptor on the host cell, c) fusion with the host cell membrane, d) delivery of viral contents.

Here's a short animation of how SARS-CoV-2 infects a cell:

 

Once the viral genome enters the lung cell, SARS-CoV-2 replicates rapidly. But how does it do this?

 

How does SARS-CoV-2 replicate?

The first step in the replication process is for the host ribosome to bind to the viral RNA and, through the process of translation, produce a protein called RNA-dependant RNA polymerase, or RdRp. RdRp is an enzyme that can produce new RNA molecules by using an existing RNA strand as a template. So once produced, the RdRp can create new copies of the viral genome (RNA). But the RdRp doesn’t always replicate the entire viral genome. Sometimes it stops early and creates shorter RNA strands, which are known as subgenomic RNAs. 

Steps of transcription of SARS-CoV-2 RNA. Illustration.

Figure 4. Viral RNA transcription.

The host ribosomes translate these pieces of subgenomic RNAs into proteins. Specific enzymes known as proteases then come along and cut these proteins into the individual structural proteins. Then, the replicated viral RNA and proteins can be packaged up into a new virus, which is released from the cell and ready to infect another cell—or another person. 

Viral protein translation and packaging into new virus. Series of four images: protein translation, protease cleavage, packaging, budding. Illustration.

Figure 5. Viral protein translation and packaging, a) short protein strands translated by host ribosomes, b) proteases cut translated protein into structural viral proteins, c) viral proteins packaged into a new viral particle, d) new viral particle budding-off from the host cell.

 

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Targeting treatments for SARS-CoV-2

Based on what we know about SARS-CoV-2 and other similar viruses, such as SARS-CoV, researchers have identified several potential treatment targets. We’ve seen how important RNA replication and protein synthesis are for viral replication, so it’s not surprising that many potential treatments target these processes. 

Remdesivir, a broad-spectrum antiviral drug, inhibits the RNA-dependent RNA polymerase and may block viral genome replication. Lopinavir-ritonavir, a drug combination used to treat HIV, binds to specific SARS-CoV-2 proteases, preventing the proper translation of viral proteins. Blocking this pathway in SARS-CoV-2 may disrupt the survival of the virus.

Treatments for SARS-Cov-2. Two boxes of antivirals (Remdesivir and Lopinavir) with mechanism of action shown. Illustration.

Figure 6. Current treatments for SARS-CoV-2 include remdesivir, which targets the RNA-dependent RNA polymerase (RdRp), and lopinavir-ritonavir, which targets the proteases. 

Of course, there are many other possible targets for therapeutics. Blocking the interaction between the spike proteins and the ACE2 receptor wouldn’t kill the virus, but it would prevent it from infecting a cell—and without a host, the virus couldn’t replicate, which would severely limit its ability to infect. 

Although we still have a lot to learn about SARS-CoV-2, understanding its basic structure and how it infects host cells is the first step to identifying potential treatment targets against it.

 

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Recommended reading

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