A variant of Covid-19 similar to the one that spread rampantly in the UK would likely have developed in Victoria during last year’s second wave had Melbourne not gone into an extended lockdown, a leading virologist says.
Associate Professor Stuart Turville from the Kirby Institute at the University of New South Wales said when his laboratory examined samples from patients as part of a study called “ADAPT” in Sydney, they started to see key differences in those infected with the virus during the second wave.
While NSW was largely spared from the second wave, some cases of the virus did make their way from Victoria to Sydney, leading to clusters associated with the Crossroads Hotel and the Thai Rock restaurant. These and other cases were captured in the ADAPT study.
Meanwhile, researchers in Melbourne were reporting a “receptor-binding domain” mutation of the virus, known as RCB. The RCB is a key part of a virus, located on its “spike” protein, that allows it to enter and infect human cells.
Turville’s team and their collaborators at Westmead hospital began matching viral flavours that were sequenced to the patients in the ADAPT study and realised that many had the RBD mutant mentioned by their Melbourne colleagues, now known as the s477n mutation.
But s477n was not detected during the first wave of infections throughout Australia. In addition to the s477n mutation, several second-wave patients had started to accumulate additional mutations.
With more than 30,000 bases, or building blocks, in its genetic material (genome), Covid-19 is thought to be quite slow-changing, accumulating approximately one or two mutations a month in its genome. The variants of concern seen in the UK, South Africa, Brazil and now elsewhere have many more changes in their genome than this, and these changes seem to make them more transmissible and possibly, in the case of the variant found in the UK, more deadly. The virus in patients from Victoria’s second wave was heading towards a similarly concerning number of changes.
“My opinion is that we might have something different now if we hadn’t literally wiped that virus, which seeded initially out of Melbourne quarantine, off of the Australian landscape,” Turville said.
Turville said s477n was concerning because it creates spike proteins – sharp bumps that protrude from the surface of the virus that help it to latch on to and infect human cells – that when combined with the right combination of other mutations in the laboratory has been shown to bind significantly more tightly to human receptor cells than the spike protein of the original virus.
“There are two observations that are of concern with s477n,” Turville said. “The first are studies where they grow virus to be resistant to antibodies. Two that emerge are s477n and e484k, with the latter observed in the South African variant. Secondly are studies that combine the elements of the s477n virus with e484k and the UK variant [n501y]. In that setting, the RBD of the virus increases its ability to bind to the receptor cells 600 times better than the original virus.”
That means it is much more infectious.
“For me, there are many variants of concern, such as those seen in South Africa, the UK and Brazil,” Turville said. “S477n was the ‘seed’ of one of them. But no one talks about this Melbourne variant anymore, because we got rid of it. But we might have dodged a bullet.”
While increased transmissibility would then be a significant risk if it mutated further, the threat of reinfection or breaking through a vaccine response would have then been an equal, if not greater, concern.
Turville and his colleagues took antibodies from patients that had recovered from the Australian first wave and then used them against the virus that appeared in the second wave. They found the s477n variant could reduce antibody binding from these patients, making the body less efficient at fighting off the virus.
“A lot of people are quite negative about the Victorian experience and the lockdown, but I’d say we did extremely well to keep that thing in the community so that it didn’t spread overseas, and to stamp it out quickly enough to keep it turning into something else,” Turville said.
“I think it had the real potential to become our own home grown variant of concern, what the world may have referred to as the ‘Australian variant’.”