A geneticist’s view of Covid-19 pandemic

SARS-CoV-2 is one of the six Coronaviruses that are known to infect humans. Covid-19 is an enveloped virus of about ~50-200 nanometer in diameter. It has a single-stranded, positive-sense RNA genome of ~30,000 nucleotides. The genome encodes 16 non-structural proteins, six accessory proteins, and four structural proteins that make the virus’s outer envelope. Covid-19 has a wide range of hosts such as birds, mammals, and humans, and they frequently jump species barriers. The virus infects humans by interacting with human Angeotensin Covering Enzyme-2 (hACE-2) receptors. Receptor binding domain of Covid-19 spike proteins interact with the human receptor. The mean generation time of Covid-19 is about 3-5 days. Geneticists around the world are trying to understand many questions about the virus; like how is the virus mutating, how are these mutations affecting its spread and evolution, and many more questions.

The term mutation usually scares people with an image of a dangerous virus with an increased ability to infect more and more people. A mutation means a change in a letter in the genetic material (DNA/RNA). Mutations are also the source of all the genetic variations in all living organisms. Mutations are random, accidental, undirected, rare, and chance events. Mutations happen spontaneously during replicating DNA with the frequency of ~1 in 1 to 10 million base pairs.

Mutations can also be induced by chemicals, radiations, and enzymes in any organism. Mutations can occur in any cell and any region of the genome of an organism. When they occur, mutations can be neutral, not affecting the organism, beneficial or harmful to an organism.

SARS-CoV-2 mutates relatively slowly compared to other viruses such as Influenza. SARS-CoV-2 acquires 2-3 mutations over a month, six times slower than the Influenza virus. When a mutation occurs, natural selection acts on the mutation. It passes it to the next generation depending on whether the mutation is neutral, beneficial, or harmful to the organism. For example, when a mutation occurs in the genome of SARS-CoV-2, it will only spread in the population rapidly, only if it has an advantage over the unmutated virus. So far, more than 15,000 mutations have been identified across all the genomes of SARS-CoV-2 sequenced. However, when two viral genomes from two patients are compared, there will be a maximum of only ten mutations. The vast majority of these mutations have no impact on the virus’s ability in transmission or virulence.

Considering the action of the mutation and selection together as a powerful evolutionary force, it is possible that new adaptive mutations could arise and be advantageous to the virus. As we know, the mutations in the receptor-binding domain of bat SARS virus spike protein have favoured the interaction with human ACE2 facilitating jumping between the hosts. Thus, it is likely that a mutation can enable the virus to escape from immune response and acquire a selective advantage in transmission. Similarly, in this course of time, the variants increase in numbers and spread with selective advantages.

Suppose the present situation is continued with the closer contact of the infected and the rest of the human population. In that case, we cannot escape from future outbreaks of the Covid pandemic.

Thus, as rightly said by Nobel Laureate Joshua Lederberg, “the single biggest threat to man’s continued dominance on the planet is the virus” has been proved true again today. As of today, we are yet to discover a specific drug to treat the covid infection completely. At present, the available vaccines can help us to develop immunity against Covid-19 infection by developing an immune response. One has to remember that the immune responses will not develop equally in all individuals but vary from person to person. It depends on the genetic and epigenetic make-up of individuals.

The only way to reduce the Covid transmission and infection is by preventing ourselves from the possibility of coming in contact with the virus. That is possible only by maintaining social distance, using sanitiser, and protecting with masks. If not, we will have the increased infections with many waves of Covid outbreaks with many new variants of the Coronavirus.

(The author is from the Department of Studies in Genetics and Genomics, Manasagangotri, University of Mysore, Mysuru)