AS COVID-19 continues to spread its tentacles across the globe, some scientists are theorising that the virus, also dubbed as SARS-CoV-2, is mutating. Understanding these mutations, which are essentially small genetic changes or “errors” in the entire genome of a virus made up of 30,000 letters, is significant for the development and evaluation of new diagnostics, drugs and vaccines.
According to a study from the Los Alamos National Laboratory in New Mexico (that has not yet been peer-reviewed), there exists a potentially more transmissible or contagious strain of the SARS-CoV-2 virus due to a mutation to the spike protein (S protein)—that mediates virus entry into host cells—called D614G. As per the study, the mutation Spike D614G is of urgent concern. It began spreading in Europe in early February. When introduced to new regions, it rapidly became the dominant form. Although the observed diversity among the SARS-CoV-2 pandemic sequences is low, its rapid global spread provides the virus with ample opportunity for natural selection to act upon rare but favourable mutations.
Spike protein is the main target of antibodies, and many vaccines are developed based on it. Mutations in virus may hamper the protection induced by a vaccine based on one variant of the spike protein.
Australia’s national science agency, Commonwealth Scientific and Industrial Research Organisation (CSIRO), further confirmed on May 12 that two-thirds of the sequenced strains globally and half of the sequences in Australia and India now have the D614G mutation which is apparently increasing its representation among newer strains. But even if a particular strain may be more transmissible, it does not mean that it will cause a more severe form of disease, says Seshadri Vasan, head of CSIRO’s Dangerous Pathogens Team, that is testing Covid-19 vaccine candidates at the Australian Centre for Disease Preparedness, Geelong. “This virus is still adapting to its new human host,” says Vasan. “It is expected that, over time, different dominant strains will appear in different parts of the world. This should not cause undue alarm. While it is normal and anticipated for RNA viruses to mutate, the SARS-CoV-2 virus has a ‘proof-reading’ mechanism which limits the rate at which it can mutate.”
Denis Bauer, team leader, Transformational Bioinformatics, CSIRO e-Health Research Program, also backs the view that mutations are a normal part of a virus’s evolution and do not necessarily have an impact on the severity of the disease.
Researchers are investigating the physical and molecular characteristics of the virus to find out significant differences and similarities it shares with other known coronaviruses which caused Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome. At the same time, as Covid-19 has turned into one of the biggest threats to the world economy, the need for testing new potential vaccines and therapeutics for the epidemic is being undertaken with a sense of urgency. CSIRO is planning experiments to confirm whether the D614G mutation will impact antibody responses to the Coalition for Epidemic Preparedness Innovations (CEPI)-funded vaccines under their evaluation.
The mutations in the Covid-19 virus are not as frequent or random as those in the case of the influenza virus for which vaccines must undergo tweaking each year for northern and southern hemispheres. Indian Immunologicals Limited, a leading vaccines manufacturing company joined hands with Griffith University of Australia to develop a live attenuated SARS–CoV-2 vaccine—which is based on a weakened version of virus—for preventive, active, single-dose immunisation. “We are fully aware that these RNA viruses have the tendency to mutate,” says Dr K. Anand Kumar, managing director, IIL. “But it is not to a level of serious concern. This mutation happens predominantly in the spike protein which is used by the virus to gain access into human cells. There are various types of vaccine manufacturers who are using different technologies, including purified spike protein as a vaccine or the whole live-attenuated virus vaccine as in our case.”
Many laboratories are cooperating to release their virus genome sequence information to the whole community. But the speed of data creation and data release, as well as the excitement to release analysis results, allows mistakes to arise, believes Nick Goldman, head of research at the European Bioinformatics Institute.
This brings us to the next obvious question: Can people be tested for all actionable mutations so that one can provide the best treatment option? Goldman says: “We do not have good treatment for any version of the virus [as of now]. We can hope in future to gain this knowledge, but for now we need to collect more data and relate the mutation data with other information such as transmissibility, severity of symptoms, effectiveness of treatment options and differential mortality.”
Dr Alejandro Cabezas-Cruz, principal investigator, UMR BIPAR (a joint research unit in molecular biology and parasitic immunology), France, says that the analysis of more than 5,300 coronavirus genomes from 62 countries shows that SARS-CoV-2 is fairly stable. “The major implication of high mutation rates in viruses is that this trait helps them escape from the immune system,” he says.
Back home, the CSIR-Central Drug Research Institute, Lucknow, has initiated collaborations with King George’s Medical University, Lucknow, to sequence the virus strains that are from patient samples in Uttar Pradesh. A team has been put into place for analysing whether changes to the viral sequences, if any, will impact proposed treatment strategies. It is known that at least eight different variants of the virus are causing the Covid-19 infection. Initially a few patient samples will be sequenced. Digital and molecular surveillance will be carried out on the basis of this work.