High mutation rate may lead to SARS-CoV-2 extinction in India

Preventive measures such as the use of institutional lockdowns around the country, the practice of physical distancing, limiting social gatherings to a minimum and good personal hygiene practices should have helped in limiting the spread of the new coronavirus infection in the country.

While there may be loopholes that may have led to a failure in controlling the number of infections, the SARS-CoV-2 virus has also been constantly evolving to thrive among the human population, even though the fatality rate has reduced. 

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The study looking into the transmission patterns of COVID-19 in India and its epidemiology, the researchers have attempted to study the mutational aspect of the spike glycoprotein in the SARS-CoV-2 virus, which is the part of the virus that binds to a receptor; ACE2 in the case of coronaviruses.

They analysed sequences of as many as 630 different isolates in the database until June 2020, and found that the spike protein variants in the Indian scenario emerged from two different varieties of the virus, the Wuhan-Hu-1/2019 and the D614G kinds. They suggest that despite the increasing number of virus mutations, the overall fatality rate has dropped.

The researchers use the model of Muller's ratchet, a theory named after Hermann Joseph Muller, which suggests that in the absence of recombination or reproduction, the resulting mutations could eventually lead to a mutational meltdown of the virus. 

Studying the virulence and efficacy of the various virus strains found in India, the researchers observed that more than half of the mutations were unique to India, but about 67% of all variants had lower stability than the variants they had evolved from, which suggests each developmental mutation could be weaker than the preceding one, despite the higher infection and mutation rate. It also explains in a way why the fatality rate in India as well as abroad has considerably come down in recent months.

The 630 different isolates or strains of the SARS-CoV-2 virus that have been found in India trace their roots back to two different mutations, namely the Wuhan-Hu-1/2019 and D614G, the latter also having evolved from the one named after the city where the virus was first discovered.

The original Wuhan-Hu-1/2019 strain of the SARS-CoV-2 virus is believed to have evolved into 20 more variants. One of those variants spawned three more, while the D614G strain, which was one of the first mutations of the original, has spawned at least 47 more. 

Nine of those have gone on to produce more variants of their own, but several studies have identified at least 16 different spike protein variants in multiple isolates with different spike protein stability. Spike protein stability indicates how viable a variant is, which helps it in attaching to the receptors in the human body to infect it.

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The lower spike protein stability observed in a majority of the mutations found in India is due to the SARS-CoV-2 virus' rapidly mutating nature being an RNA type virus. Applying the Muller's ratchet here, many of the mutations may naturally die out due to the irreversible effects of asexual reproduction.

The researchers conclude by saying that due to the limitations in the duration of the study, more studies need to be conducted in this field to correlate the high number of mutations with the falling fatality rates. These types of studies are also critical in observing infection rates in a population, just as it is in identifying new treatment strategies as well as in vaccine development. However, larger studies need to be performed in order to ascertain the role of mutations in eventually triggering a meltdown of the SARS-CoV-2 virus.