Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a robust virus belonging to the subgenus Betacoronavirus and is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. In the initial stages of the pandemic, the virus was limited in diversity, with very little deviance from the original virus genome.
However, in the past year, numerous mutant variants have been identified, with mutations associated with antibody evasion, increased transmissibility, and potentially more severe virulency.
In a short article recently published in Science, researchers summarize what this rapid increase of plasticity of SARS-CoV-2 could mean for the future of the pandemic and anti-SARS-CoV-2 measures.
The article can be accessed from Science Magazine online.
What is meant by plasticity?
In biological terms, plasticity refers to an organism’s ability to adapt to changes in its environment. For viruses, greater plasticity usually refers to the speed at which a virus may be able to acquire advantageous mutations – the faster these mutations tend to crop up in changing environments, the more plastic a virus is considered to be.
During the first wave of the COVID-19 pandemic, the vast majority of cases were caused by the ancestral Wuhan-Hu-1 strain of SARS-CoV-2. Since then, multiple variants have arisen around the world, with mutations predominantly in the spike (S) protein. These mutations have often appeared convergently, suggesting potential pathways of evolution.
Increased plasticity ultimately may mean that the viruses are predisposed to acquiring mutations that allow for antibody evasion or increased transmissibility.
“The growing evidence for the emergence of immune escape mutations in protracted SARS-CoV-2 infection and for multiple, rapidly spreading variants should raise broad concern and action,” say the researchers.
What mutations are of concern?
Perhaps the most significant mutation observed in SARS-CoV-2 is the D614G substitution in the S1 subunit of the S protein. D614G is associated with increased binding affinity with human angiotensin-converting enzyme 2 (ACE2), an enzyme found on the cell membranes of cells predominantly found in the respiratory and pulmonary systems, and seems to have convergently appeared in three main variants of concern (VoCs): the UK (B.1.1.7), South African (B.1.351), and Brazilian (P.1) variants.
This mutation seems to increase ACE2 affinity at the expense of reduced resistance to antibodies. Another mutation, E484K, increases resistance to antibodies, but is less infectious. Interestingly, VoC strains have acquired additional mutations that restore abilities lost through previous mutations. Notable examples of these include the deletion (D) of amino acids 69—70, 141—144, and 242—248 in S1, and also the substitutions K417N and N501Y.
How has plasticity increased in SARS-CoV-2?
These notable mutations that have appeared repeatedly and independently in VoCs were identified in five patients predating the detection of B.1.1.7, B.1.351, and P.1. The authors speculate that these arose due to selective pressures over the course of 2020, as very few mutations of SARS-CoV-2 were circulating for much of the year.
It is unlikely that these mutations have arisen multiple times by chance, implying the presence of a strong environmental pressure for these to evolve.
It is currently unknown whether novel antibody therapies have played a role in this or not. However, further mutations of similar natures are presumed to continue arising if the same selective pressure is applied. The B.1.1.7 variant, in particular, has been of concern as it appears to resist neutralization from the Pfizer/BioNTech vaccine.
Recent studies also suggest B.1.351 has increased antibody evasion, and that vaccines thus offer less protection from it. Some researchers suspect that this variant may contain currently uncharacterized mutations, which may facilitate this ability, although further study is needed.
The researchers push for increased genomic and phenotypic testing abilities for SARS-CoV-2, to quickly identify and characterize novel circulating variants.
The increasing prevalence of SARS-CoV-2 variants with antibody evasive properties and increased virulence should be of principal concern when dealing with the ongoing COVID-19 pandemic.