Mutation in coronavirus from India random, no cause for alarm

The new study found a mutation in the mechanism Sars-CoV-2 the virus that causes Covid-19, uses to enter the human cells in the strains isolated from one of the first three cases of Covid-19 in Kerala on January 27, which was the first case of the disease in India.

A mutation in the coronavirus strain isolated in India has the potential to jeopardise global efforts to develop a vaccine against coronavirus disease (Covid-19), which has infected 2 million people and killed at least 26,000 in four months, according to a preliminary analysis of 106 Sars-CoV-2 and 39 SARS genome sequences.

Leading scientists, however, warn against reliance on a single sample with a variation and say further confirmation is needed at sequence and protein level for conclusive evidence. (Reuters file photo. Representative image)

Leading scientists, however, warn against reliance on a single sample with a variation and say further confirmation is needed at sequence and protein level for conclusive evidence.

The new study found a mutation in the mechanism Sars-CoV-2 the virus that causes Covid-19, uses to enter the human cells in the strains isolated from one of the first three cases of Covid-19 in Kerala on January 27, which was the first case of the disease in India. The findings were published in the preprint server bioRxiv, which puts scientific papers in the public domain before peer-review.

Sars-CoV-2 consists of a strand of RNA enclosed in shell covered with crown-like spikes (explaining its name; ‘corona’ is the Latin word for crown). Most vaccine and drug development efforts are focusing on stopping the action of the viral spike (S) protein that it uses to enter human cells, where it replicates to cause infection.

The study found changes in a part of the spike protein that allows the virus to bind to and penetrate human cells. This spike protein targets cells containing ACE-2 (angiotensin converting enzyme-2), a protein found on lung, kidney, heart, and gut cells in humans. ACE-2 has several roles, including modulating blood pressure and immune response.

“We identified a mutation that leads to weaker receptor binding capability, which concerns a Sars-CoV-2 sample collected on 27th January 2020 from India. This represents the first report of a significant Sars-CoV-2 mutant, and raises the alarm that the ongoing vaccine development may become futile in future epidemic if more mutations were identified,” write study authors from Australia and Taiwan.

“The observation of this study raised the alarm that Sars-CoV-2 mutation with varied epitope (that antibodies bind to) profile could arise at any time,” said the study, which also provided direct genetic evidence that Sars-CoV-2 has a much lower mutation rate than Sars-CoV, the virus that causes severe acute respiratory syndrome.

Monitoring the mutation dynamics of Sars-CoV-2 is critical for the development of effective approaches to develop drugs and vaccines to contain the pathogen. “The lower receptor fit may make virus less efficient in transmission, but then we need to watch out for a change in virulence also. As of now this paper, it is ‘curiosity’ information. We have to wait and watch,” said Dr T Jacob John, professor emeritus and former head of virology at Christian Medical College, Vellore, Tamil Nadu.

The mutation appears to be random and not the result of natural selection by the immune system because there were no more variants in that part of the spike than elsewhere in the genome, say scientists.

“The study is too preliminary and lays too much reliance on a single sample with a variation that has been previously discussed. Unless one sees this confirmed further at sequence and protein level studies, at the minimum, no conclusion can be reached. Definitive conclusion will require proper virological studies,” said Dr Anurag Agarwal, director, CSIR-Institute of Genomics & Integrative Biology, Delhi.

Most work on vaccines, drugs and therapies is targeting the spike (S) protein to prevent from binding to the ACE-2 that it sues as a receptor to enter cells. Five Covid-19 vaccine candidates are in phase 1 clinical trials to establish safety for humans and 73 in exploratory or preclinical stages, a vaccine is likely to be ready in early 2021, according to an analysis of the global Covid-19 vaccine database of Coalition of Epidemic Preparedness (Cepi), one of the world’s biggest public funders of vaccine development. The analysis was published in the journal Nature Reviews Drug Discovery on April 11, just three months of China sharing the first genetic sequence of the virus on January 12.