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Scepticism greets China study that links snakes to coronavirus outbreak

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As human cases rise in a mysterious viral outbreak that originated in China, scientists are rushing to identify the animals, where they suspect the epidemic began. In a controversial study, a team of researchers in China claimed to have an answer: snakes. But other scientists say there is no proof that viruses such as those behind the outbreak can infect species other than mammals and birds. “Nothing supports snakes being involved,” says David Robertson, a virologist at the University of Glasgow, UK.

Many scientists suspect that an unknown animal carrying 2019-nCoV spread the virus to humans at a live seafood and wild animal market in Wuhan, where the first cases were documented in December. “The intermediate host is the missing piece of the puzzle: how have all these people got infected?” says Robertson.

A team led by Wei Ji, a microbiologist at Peking University Health Science Centre School of Basic Medical Sciences in Beijing, looked for a sign that 2019-nCoV had adapted to any specific animal host. The team reported that 2019-nCoV’s choice of codons was most similar to those used by two snakes: Bungarus multicinctus (the many-banded krait) and Naja atra (the Chinese cobra). Snakes were sold at the Wuhan seafood and animal market, the researchers note. “Taken together, snakes could be the most likely wildlife animal reservoir for the 2019-nCoV,” they write.

Robertson says it’s unlikely that 2019-nCoV has infected any secondary animal host for long enough to alter its genome significantly. “It takes a long time for such a process to play out,” he says.

“They have no evidence snakes can be infected by this new coronavirus and serve as a host for it,” says Paulo Eduardo Brandão, a virologist at the University of São Paulo who is investigating whether coronaviruses can infect snakes at all. “There’s no consistent evidence of coronaviruses in hosts other than mammals and Aves (birds).”

Wei’s team has not yet responded to e-mails from Nature’s news team seeking comment on the paper and the criticism it has received.

Many researchers are sceptical that the animal host or hosts of 2019-nCoV can be identified without further field and laboratory work. Many hope that genetic tests of animals or environmental sources, such as cages and containers, from the Wuhan market will turn up clues.

The study notes that patients who became infected with the virus – which was named 2019-nCoV by the World Health Organisation – were exposed to wildlife animals at a wholesale market, where seafood, poultry, snake, bats, and farm animals were sold.

By conducting a detailed genetic analysis of the virus and comparing it with available genetic information on different viruses from various geographic locations and host species, the investigators concluded that the 2019-nCoV appears to be a virus that formed from a combination of a coronavirus found in bats and another coronavirus of unknown origin. The resulting virus developed a mix or “recombination” of a viral protein that recognises and binds to receptors on host cells. Such recognition is key to allowing viruses to enter host cells, which can lead to infection and disease.

Finally, the team uncovered evidence that the 2019-nCoV likely resided in snakes before being transmitted to humans. Recombination within the viral receptor-binding protein may have allowed for cross-species transmission from snake to humans.

“Results derived from our evolutionary analysis suggest for the first time that snake is the most probable wildlife animal reservoir for the 2019-nCoV,” the authors wrote. “New information obtained from our evolutionary analysis is highly significant for effective control of the outbreak caused by the 2019-nCoV-induced pneumonia.”

An accompanying editorial notes that although the ultimate control of emerging viral infections requires the discovery and development of effective vaccines and/or antiviral drugs, currently licensed antiviral drugs should be tested against the 2019-nCoV.

Abstract
The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by a novel coronavirus designated 2019-nCoV by the World Health Organization, as determined by sequencing the viral RNA genome. Many patients were potentially exposed to wildlife animals at the Huanan seafood wholesale market, where poultry, snake, bats, and other farm animals were also sold. To determine the possible virus reservoir, we have carried out comprehensive sequence analysis and comparison in conjunction with relative synonymous codon usage (RSCU) bias among different animal species based on existing sequences of the newly identified coronavirus 2019-nCoV. Results obtained from our analyses suggest that the 2019-nCoV appears to be a recombinant virus between the bat coronavirus and an origin-unknown coronavirus. The recombination occurred within the viral spike glycoprotein, which recognizes cell surface receptor.
Additionally, our findings suggest that snake is the most probable wildlife animal reservoir for the 2019-nCoV based on its RSCU bias resembling snake compared to other animals. Taken together, our results suggest that homologous recombination within the spike glycoprotein may contribute to cross-species transmission from snake to humans.

Authors
Ji W, Wang W, Zhao X, Zai J, Li X

Nature material

Journal of Medical Virology abstract

Wiley material

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