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SARS-CoV-2 genomic landscape

Overview of the genomic landscape of the SARS-CoV-2 virus.

All of us have been impacted in some way by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). You are likely to be familiar with a city in China that you never heard of before the pandemic, Wuhan – where this virus was isolated in 2019.

SARS-CoV-2 is a single-stranded RNA virus of ~30 Kb (positive sense) (Figure 1). Despite being incredibly small, compared to the human genome, which is approximately 6 Gbp, SARS-CoV-2 is the largest known RNA virus. SARS-CoV-2 has a crown-like shape which contains four main structural proteins, namely the: spike (S), envelope (E) glycoprotein, nucleocapsid (N), membrane (M) protein, along with 16 nonstructural proteins, and 5-8 accessory proteins.

We are interested in the structure of a virus/organism because it gives us information about how the virus is able to shed, spread, infect and subsequently cause disease (pathogenesis).

Esquematic illustration of SARS-CoV-2: a purple sphere covered with green spikes. Spike, Nucleocapsid, Membrane, Envelope and ssRNA are indicated inside the sphere

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Making sense of genomic data: COVID-19 web-based bioinformatics

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Figure 1 – The SARS-CoV-2 virus with its proteins. Source Frontiers

The accessory proteins participate in the viral replication, assembly and in virus-host interactions.

The non-structural proteins are like maintenance workers which act as enzymes, coenzymes, and binding proteins to facilitate the replication, transcription, and translation of the virus.

Finally, the structural proteins are essential for the host cells’ binding and invasion. The 3D shape of a spike protein is shown in Figure 2 below. This protein allows the virus to enter human cells by binding to human ACE receptors in the respiratory epithelium.

This article provides a detailed explanation of this process.

Illustrative image of the SARS-CoV-2 genome and its proteins: a bar with rectangles representing SARS-CoV-2 genes and protein structures of protease, endoribonuclease and spike

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Figure 2 – Various enzymes and the spike protein of SARS-CoV-2. Source: StatPearls Publishing LLC

The spike proteins are also frequently the site of mutations, resulting in diverse new variants. Mutations are natural random events which occur in viruses during replication. A variant has one or more mutations that may allow it to be distinct in its transmissibility, virulence, pathogenicity or response to vaccines. Currently, variants have been grouped into four different categories which are: a Variant of Interest (VOI), a Variant Being Monitored (VBM), a Variant of High Consequence (VOHC) and a Variant of Concern (VOC).

This article provides a detailed explanation of this process and you can read more about these proteins in here

A VOC usually contributes to outbreaks due to its increased transmission fitness and/or immune evasion ability. The most notable VOCs are currently called Alpha, Beta, Gamma and Delta; firstly described in the United Kingdom, South Africa, Brazil and India, respectively. The latest and most transmissible variant has been labelled Omicron, which was also first reported in South Africa. The location of where variants are first described is highly linked to the amount and quality of genomic surveillance occurring in a particular country. We can only find variants if we are looking for them at a genomic level.

The CDC’s website has up-to-date information to keep you abreast of the range of variants.

Mutations may also lead to the formation of new lineages. Lineages are described as being a genetically closely related group of viral variants which are derived from a common ancestor. Tracking lineages informs us of outbreaks and of the spread of a virus in a community or within populations.

Zoonotic coronaviruses have caused several outbreaks over the last two decades and many of the coronaviruses present in other mammals have the potential to infect humans. Therefore our continuous efforts to understand the origins and evolution of SARS-CoV-2 will remain critical.