Analysis-In mutant variants, has the coronavirus shown its best tricks?

By Kate Kelland and Julie Steenhuysen

LONDON/CHICAGO (Reuters) – The rapid rise in different parts of the world of deadly, more infectious coronavirus variants that share new mutations is leading scientists to ask a critical question – has the SARS-CoV-2 virus shown its best cards?

New variants first detected in such far-flung countries as Brazil, South Africa and Britain cropped up spontaneously within a few months late last year. All three share some of the same mutations in the important spike region of the virus used to enter and infect cells.

These include the E484k mutation, nicknamed “Eek” by some scientists for its apparent ability to evade natural immunity from previous COVID-19 infection and to reduce protection offered by current vaccines – all of which target the spike protein.

The appearance of similar mutations, independent of one another, springing up in different parts of the globe shows the coronavirus is undergoing “convergent evolution,” according to a dozen scientists interviewed by Reuters.

Although it will continue to mutate, immunologists and virologists said they suspect this coronavirus has a fixed number of moves in its arsenal.

The long-term impact for the virus’ survival, and whether a limit on the number of mutations makes it less dangerous, remains to be seen.

“It is plausible that this virus has a relatively limited number of antibody escape mutations it can make before it has played all of its cards, so to speak,” said Shane Crotty, a virologist at the La Jolla Institute for Immunology in San Diego.

That could enable drugmakers to stay on top of the virus as they develop booster vaccines directly targeting current variants, while governments struggle to tame a pandemic that has killed nearly 3 million people.

The idea that the virus could have a limited number of mutations has been circulating among experts since early February, and gathered momentum with the posting of a paper showing the spontaneous appearance of seven variants in the United States, all in the same region of the spike protein.

EVOLUTION, IN REAL TIME

The process of different species independently evolving the same traits that improve survival odds is central to evolutionary biology. The vast scope of the coronavirus pandemic – with 127.3 million infections globally – allows scientists to observe it in real time.

“If you wanted to sort of write a little textbook about viral evolution, it’s happening right now,” Dr. Francis Collins, a geneticist and director of the U.S. National Institutes of Health, said in an interview.

Scientists saw the process on a smaller scale in 2018 as a dangerous H7N9 bird flu virus in China appeared to begin adapting to human hosts. But no pathogen has evolved under such global scrutiny as SARS-CoV-2.

Wendy Barclay, a virologist and professor at Imperial College London and a member of a scientific advisory panel to the UK government, said she is struck by the “amazing amount of convergent evolution we’re seeing” with SARS-CoV-2.

“There are these infamous mutations – E484K, N501Y and K417N – which all three variants of concern are accumulating. That, added together, is very strong biology that this is the best version of this virus in the given moment,” Barclay said.

It’s not that this coronavirus is especially clever, scientists said. Each time it infects people it makes copies of itself, and with each copy it can make mistakes. While some mistakes are insignificant one-offs, the ones that give the coronavirus a survival advantage tend to persist.

“If it keeps happening over and over again, it must be providing some real growth advantage to this virus,” Collins said.

Some specialists believe the virus may have a limited number of mutations it can sustain before compromising its fitness – or changing so much it is no longer the same virus.

“I don’t think it’s going to reinvent itself with extra teeth,” said Ian Jones, a professor of virology at Britain’s University of Reading.

“If it had an unlimited number of tricks…we would see an unlimited number of mutants, but we don’t,” said Michel Nussenzweig, an immunologist at Rockefeller University in New York.

CAUTIOUS OPTIMISM

Scientists remain cautious, however, and say predicting how a virus will mutate is challenging. If there are limits on how the coronavirus can evolve, that would simplify things for vaccine developers.

Novavax Inc is adapting its vaccine to target the South African variant that in lab tests appeared to render current vaccines less effective. Chief Executive Stan Erck said the virus can only change so much and still bind to human hosts, and hopes the vaccine will “cover the vast majority of strains that are circulating.”

If not, Novavax can continue matching its vaccine to new variants, he said.

Researchers are tracking the variants through data-sharing platforms such as the Global Initiative on Sharing Avian Flu Data, which houses a huge trove of coronavirus genomes.

Scientists recently identified seven U.S. coronavirus variants with mutations all occurring in the same location in a key portion of the virus, offering more evidence of convergent evolution.

Other teams are conducting experiments that expose the virus to antibodies to force it to mutate. In many cases, the same mutations, including the infamous E484K, appeared.

Such evidence adds to cautious optimism that mutations appear to share many of the same traits.

But the world must continue tracking changes in the virus, experts said, and choke off its ability to mutate by reducing transmission through vaccinations and measures that limit its spread.

“It’s shown a very strong set of opening moves,” Vaughn Cooper, an evolutionary biology specialist at the University of Pittsburgh School of Medicine, said of this coronavirus. “We don’t know what the end game is going to look like.”

India warns of worsening COVID-19 situation, vaccinations to expand

By Krishna N. Das and Neha Arora

NEW DELHI (Reuters) – India announced an expansion of its COVID-19 vaccination program on Wednesday but warned that breaches of coronavirus protocols could worsen an infection surge in many states.

Nearly a month after the health minister declared that COVID-19 had been contained, states such as Maharashtra in the west and Kerala in the south have reported a spike in cases amid growing reluctance to wear masks and maintain social distancing.

India’s infections are the second highest in the world at 11.03 million, swelled by a further 13,742 in the past 24 hours, health ministry data showed. Deaths rose by a two-week high of 104 to 156,567.

“Any laxity in implementing stringent measures to curb the spread, especially in view of new strains of virus…, could compound the situation,” the ministry said in a statement singling out nine states and a federal territory.

India has confirmed the long-time presence of two mutant variants – N440K and E484Q – in addition to those first detected in Brazil, Britain and South Africa.

TESTS FALLING

The health ministry said that while cases in the states of Chhattisgarh, Gujarat, Kerala, Maharashtra, Madhya Pradesh and Punjab, as well as the federal territory of Jammu and Kashmir, were rising, the proportion of high-accuracy RT-PCR tests in those places was falling because many states prefer antigen tests, which are cheaper and quicker but less accurate.

The federal government is worried excessive reliance on rapid antigen tests could undercount cases, leading to real infections going unchecked and spreading the disease.

Cases have also risen in Karnataka, Tamil Nadu and West Bengal.

In the past week, a third of India’s 36 states and union territories have reported an average of more than 100 new cases each day, with Kerala and Maharashtra both registering more than 4,000, in a trend experts link to the reopening of schools and suburban train services.

Maharashtra reported 8,807 new COVID-19 cases on Wednesday, the highest in nearly five months. Of those, 1,167 were in Mumbai, India’s financial capital.

The government has also asked states to speed up vaccinations for healthcare and frontline workers. Just about 11 million people have received one or two doses in a campaign that began on Jan. 16. The target is 300 million by August.

From March 1, India will start vaccinating people above 60 and those older than 45 with health conditions free of charge in about 10,000 government hospitals and for a fee in more than 20,000 private facilities, the government said.

Earlier on Wednesday, a regulatory panel sought more data from drugmaker Dr. Reddy’s Laboratories for emergency authorization of Russia’s Sputnik V COVID-19 vaccine, a senior official with direct knowledge of the discussions said.

The Central Drugs Standard Control Organization did not immediately reply to a Reuters request for confirmation.

(Reporting by Krishna N. Das and Neha Arora; Additional reporting by Rajendra Jadhav; Editing by Mark Heinrich)