The world is filled with various colours of roses. We have pink, red, white, and even orange roses. The diversity in the colour of roses, and, in general, the colour of many types of flowers, is due to genetic mutations, which in its most basic form can be defined as changes in the nucleotide sequence (DNA* or RNA**) of a biological entity. For more information about genetic mutations and how they affect us, please check here for more detail.
Viruses*** are prone to mutations, and these mutations can even be viewed as an inescapable consequence in the viral life cycle [1]. As viruses replicate their genomes, they tend to create errors during the process – these errors are known as variants. For the most part, these mutations are neutral or disadvantageous, and viruses possessing them are usually removed from the population. However, if a mutation increases the transmission of a virus – the ease at which it can replicate or the ability of the virus to evade its host immune system – they obtain an advantage. Consequently, these viruses can become the dominant variant in a population. These dominant variants are now considered strains [2]. Essentially, all strains are variants, but not all variants are strains.
Variants of SARS-CoV-2
In general, RNA viruses tend to have higher mutation rates in comparison to DNA viruses because there are not as many proteins**** to ensure that the replication is correct – this is called proofreading machinery. However, unlike most other RNA viruses, coronaviruses possess a proofreading machinery that reduces the occurrence of mutations during the replication process [3]. In spite of this, since the inception of the pandemic, SARS-CoV-2 has produced multiple variants. The World Health Organization (WHO) has detected that there are currently 8 different variants of the virus so far. Variants are further divided into Variants of Concern (VOCs) and Variants of Interest (VOIs) [4].
Variants of Concern (VOC)
The WHO classifies a variant as a VOC if:
It has an increased capacity to be transmitted.
It increases virulence (the capacity to cause damage to the host).
It is more detrimental to public health.
It decreases effectiveness in vaccines or therapeutics.
There are changes in clinical disease manifestation. For example, if COVID-19 starts affecting feet rather than the lungs, it will take more time for doctors to realize that the patient has COVID, thus delaying the treatment and giving more time for the virus to spread.
Within this category are the four well-known SARS-CoV-2 variants, which are variants named Alpha, Beta, Gamma, and Delta [4].
The Alpha variant, also known as variant B.1.1.7, was first identified in the United Kingdom in September 2020, but was not given a full VOC classification until December 2020. It quickly became the dominant circulating strain in England at the end of 2020 [5]. This variant owes its increased transmissibility to the 9 mutations in its spike (S) protein, in comparison to the original genetic sequence of SARS-CoV-2 [6]. More information about S protein here.
The Beta variant, or B.1.351, is better known as the South African variant. It was first identified in May 2020, and officially classified as VOC in December 2020 [5]. It contains 10 mutations in its sequence of the S protein, which also increased its transmissibility. Along with the Alpha variant, the Beta variant was also able to spread globally and caused considerable concern.
The Gamma variant, or P.1, is better known as the Brazilian variant. It first was identified in Brazil in November 2020, and officially became a VOC in January 2021 [5]. Like its previous VOCs, there are mutations in its gene for the S protein (in this case, there are 12 mutations), however, this mutation confers a selective advantage. In other words, it has an enhanced survival.
The Delta variant, or B.1.617.2, is the newest VOC, and has gained considerable attention over the past few months. It was identified in India in October 2020 and became an official VOC in May 2021 [5]. Similar to the other VOCs, the majority of its mutations are in the S protein. What makes this variant so alarming is the fact that it is believed to be more transmissible than the other variants [7]. Moreover, compared to the other VOCs, vaccines seem to be less effective [8].
Variants of Interest (VOI)
The WHO designates VOIs as variants that [5]:
Possesses genetic mutations that are predicted or known to modify the transmissibility of the virus.
Are easier to diagnose and treat.
Are less severe, even though they are more transmissible.
Show an increase in the number of cases.
As a result of these characteristics, VOIs are seen as an emerging risk to global public health that need to be closely monitored. There are 4 VOI variants classified by WHO:
The Eta variant, which was first identified in multiple countries in December 2020, presumably due to its delayed detection.
The Iota variant, which was first identified in the USA in November 2020.
The Kappa variant, which was identified in India in October
The Lambda variant, which was identified in Peru in December 2020.
So far, current vaccines have shown to neutralize these variants, which means that we are protected against these new variants. Next week, we will discuss this topic in more depth.
*DNA - deoxyribonucleic acid, one of the nucleic acids found in living cells. DNA is formed by 4 nucleotides, which can be organized in different sequences and different lengths like letters are organized to form a text. In this case, the “text” formed by the sequence contains the instructions to form a whole organism. DNA is normally found as a paired double strand, in a double helix shape.
*RNA - ribonucleic acid, one of the nucleic acids found in cells. It is transcribed from DNA. There are many types of RNAs, some of which can have a specific function controlling or regulating some processes in cells while others (known as messenger RNAs, or mRNAs) carry the genetic information that can be translated into proteins by ribosomes.
*Virus - it can be considered a very small and basic life form or an aggregate of molecules that is simpler than a cell. They can be found in the environment or inside living organisms. It has to infect a cell and use its machinery to multiply, since it cannot multiply by itself. Viruses consist of nucleic acids (DNA or RNA), a protein capsid that contains the nucleic acids and, sometimes, an external envelope of lipids. The flu, measles, AIDS and Covid-19, for instance, are caused by viruses.
*Protein - a molecule that forms the structure and gives function to organisms at the most basic level. Proteins consist of amino acids, which can be combined in different sequences to form different protein structures with different functions in cells.
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Written by: Renard
Edited by: María and Natasha
BioDecoded is a volunteer group committed to sharing accurate scientific information. If you have any questions about this topic, please comment or send them to our email.
References:
Grubaugh, N., Petrone, M. & Holmes, E. We shouldn’t worry when a virus mutates during disease outbreaks. Nature Microbiology 5, 529-530 (2020). https://www.nature.com/articles/s41564-020-0690-4
Lauring, A. & Hodcroft, E. Genetic Variants of SARS-CoV-2—What Do They Mean?. JAMA 325, 529 (2021). https://jamanetwork.com/journals/jama/fullarticle/2775006
Smith EC, Blanc H, Vignuzzi M, Denison MR. Coronaviruses Lacking Exoribonuclease Activity Are Susceptible to Lethal Mutagenesis: Evidence for Proofreading and Potential Therapeutics. PLoS Pathog 9(8): e1003565 (2013). https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1003565
Tracking SARS-CoV-2 variants. World health organization (2021). Available at: https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/ (Accessed: 26th July 2021)
Public Health England. Investigation of novel SARS-CoV-2 variant: variant of concern 202012/01, technical briefing 3. London, United Kingdom: Public Health England; (2020). Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/950823/Variant_of_Concern_VOC_202012_01_Technical_Briefing_3_-_England.pdf
Zhou, D. et al. Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera. Cell 184, 2348-2361.e6 (2021). https://www.sciencedirect.com/science/article/pii/S0092867421002269
Public Health England. SARS-CoV-2 variants of concern and variants under investigation in England—technical briefing 17. London, United Kingdom: Public Health England (2021). https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/997418/Variants_of_Concern_VOC_Technical_Briefing_17.pdf
Planas, D. et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature (2021). https://www.nature.com/articles/s41586-021-03777-9
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