Darwin’s finches!

Contributed by Dr Selwyn Selvakumar, CMC, Vellore

New mutations of the SARS-CoV-2 virus continue to be discovered since the beginning of the pandemic. The question we need to answer is, are these variants harmful? When we look at the way how the virus has evolved, it gives some sense of what will happen next. When the pandemic started, the D614G mutant strain was the one that spread at an alarming pace from Wuhan to Europe. D614G mutation is located between S1-RBD and S2 junctions of the SARS-CoV-2 spike (S) protein. Hence a new elastase-specific proteolytic cleavage site, therefore enjoys a double advantage in its ability to gain entry into human cells. By the end of February 2020, the frequency of specific clade of D614G, A2a rose from 9% to 56.25% in Europe and 0% to 9.7% in North America which was not prevalent in Asia and China at that time. From the beginning of August 2020, multiple crops of variants became dominant in different parts of the world such as the B.1.1.7 variant in the UK, the South African variant (B.1.351), and the Brazilian variant (P.1). Each variant had multiple mutations, especially the Variant Of Concern (VOC) B.1.1.7 consisting of 23 different mutations, among which 8 were in the spike region and D614G is one of them. R-value for B.1.1.7 was consistently higher (x 1.47) at any given time. When we talk about India’s second wave, all the three variants mentioned earlier had played a part, but the one that dominated was B.1.617.2. This was first detected in India in December 2020. It remained rare until early March 2021 when it became the dominant variant. Among the many mutations, it consists of three that are found in spike protein, known as L452R and E484Q, V382L and so it is called a triple mutant.

Different variants throughout the pandemic are a great example the Darwinian theory of natural selection, evolution, and even the origin of species can be observed in real-time. The variants are genetically distinguishable and different in their biology due to benefit mutation. These changes can affect the behavior of the virus with respect to infectivity, pathogenicity, and sensitivity to the neutralizing antibodies. Since it is a rule that like all RNA viruses, Coronaviruses will mutate (but has proofreading ability!), variants are expected. Variants we identified so far is only 0.004% of the world cases, which is indicative of the limits of genomic surveillance. To a certain extent, the rise of mutant viruses is a numbers game. The more the host availability, the more likely it is that a variant with beneficial mutations will become prominent. In a bird’s eye view, lack of host availability can smother mutations that arise because it limits the transmission to the next host.

Currently available vaccines elicit a broad immune response with a wide range of targets. Therefore, it is unlikely that few mutations would allow for complete immune escape. And while there haven’t been any comprehensive studies so far, it does appear that vaccines offer adequate protection against these new strains.

Lessons Learnt

  1. Variants are the rule in RNA virus infections
  2. Reducing human to human transmission can halt the evolution of mutant strains
  3. Vaccines will work against the variants

References

  1. https://cals.ncsu.edu/applied-ecology/news/a-primer-on-coronavirus-variants-mutation-and-evolution/
  2. https://www.who.int/news-room/feature-stories/detail/the-effects-of-virus-variants-on-covid-19-vaccines