A mutation in the coronavirus strain isolated in India has the potential to jeopardise global efforts to develop a vaccine against Covid-19, which has infected 2 million people and killed at least 126,000 in four months, according to a preliminary analysis of 106 Sars-CoV-2 and 39 SARS genome sequences.
Scientists, however, warn against reliance on a single sample and say further confirmation is needed.
The mutation was in the mechanism the virus uses to enter human cells. It was found in the strains isolated from a case in Kerala on January 27. 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 spikes. Most vaccine and drug development efforts are focusing on stopping the action of the spike protein.
The study found changes in a part of the spike protein that allows the virus to bind to and penetrate cells. This protein targets cells containing ACE-2, a protein found in lung, kidney, heart, and gut cells in humans.
“We identified a mutation that leads to weaker receptor binding capability…. 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,” wrote the study’s authors from multiple institutions in Australia and Taiwan.
The study 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.
“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, 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 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,” said Dr Anurag Agarwal, director, CSIR-Institute of Genomics & Integrative Biology, Delhi.
Most work on vaccines and drugs is targeting the spike protein to prevent it from binding to the ACE-2. Five 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 vaccine database of Coalition of Epidemic Preparedness (Cepi), one of the world’s biggest public funders of vaccine development. The analysis was published in Nature Reviews Drug Discovery .
