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Experts are concerned about the coronavirus spreading from humans to animals, and the implications of infected animals spreading the virus unchecked. Author and journalist David Quammen joins CBSN’s Anne-Marie Green and Vladimir Duthiers to discuss why the U.S. wasn’t more prepared for a pandemic to emerge and how the virus can spread between species.
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Scientists report exceptional selection pressure on coronavirus host receptors in bats compared to other mammals
The current coronavirus disease 2019 (COVID-19) pandemic occurred due to the zoonotic spillover of a novel coronavirus, namely, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic has highlighted the importance of understanding how pathogens (e.g., bacteria, fungi, and viruses) and hosts co-evolve in response to each other.
Study: Exceptional diversity and selection pressure on coronavirus host receptors in bats compared to other mammals. Image Credit: Rudmer Zwerver/Shutterstock BackgroundBased on the evolutionary analysis, researchers reported that hosts encounter immense pressure because of the proteins that are targeted during infection. In response to this event, they naturally evolve, such that the proteins are no longer targeted by pathogens.
Several studies have indicated that bats are a potential reservoir of emerging infectious viruses, especially coronaviruses. These studies have revealed that three of the most infectious coronaviruses, namely, SARS-CoV-2, Middle Eastern respiratory syndrome-associated coronavirus (MERS-CoV), and severe acute respiratory syndrome-associated coronavirus (SARS-CoV), have originated from bats.
Scientists stated that based on the evolutionary histories of bat species, the virus has changed its characteristic features with varying levels of infectiousness and response to the host’s immunity. Hence, it is extremely important to investigate all species to determine the one with a higher level of risk of zoonotic spillover to humans or vice versa.
Investigation of host proteins associated with potential zoonoses could be a powerful indicator for determining the past as well as present proteins, which are under potential evolutional pressure. Evaluation of these proteins could also predict the possibility of cross-species transmission. Several studies have attempted to elucidate how different strains of the virus can bind with different species’ angiotensin-converting enzyme 2 (ACE2) and dipeptidyl-peptidase 4 (DPP4), which could lead to zoonotic spillovers.
A new studyA new study examined how ACE2 and DPP4 has evolved using the bat genetic dataset as well as other mammal species. Both ACE2 and DPP4 are the prime receptor proteins that have been targeted by SARS-CoV and SARS-CoV-2, and MERS-CoV, respectively. This study has been published in Proceedings of the Royal Society B.
In this study, researchers utilized ACE2 and DPP4 sequences from fifty-five bat species representing five families and thirty-seven genera to analyze their evolution. Scientists obtained the ACE2 and DPP4 sequences and mammalian ACE2 and DPP4 orthologues from Gen-Bank. Scientists conducted phylogenetic and molecular analyses to identify the evolutionary diversities and similarities.
Researchers compared amino acid sequences associated with ACE 2 for SARS-CoV and SARS-CoV-2, and DPP4 for MERS-CoV, to understand and detect which amino acid residues were responsible for coronavirus binding across mammals. This was also useful in determining the probable host range of these coronaviruses.
Shannon’s diversity index was calculated to identify which amino acid positions were the most variable. Scientists determined the number of unique amino acids and their evenness for positions using vegan packages in R. They further analyzed amino acid residues that were identical or equivalent to humans.
Key findingsIn this study, scientists analyzed around 270 ACE2 sequences from 206 species, i.e., 98 bat and 108 non-bat species. Additionally, they evaluated 248 DPP4 sequences from 235 species, which included 92 bat and 143 non-bat species. Although many non-bat mammal species were present, scientists observed a higher number of unique combinations in bats compared to non-bat species. This study documents that bats are diverse at ACE2 contact amino acid residues for SARS-CoV and SARS-CoV-2 and DPP4 contact residues for MERS-CoV.
Scientists conducted several selection analyses using the recent mammalian maximum class credibility (MCC) tree, which indicated that bats were under positive selection in contact residues. Additionally, other analyses, such as the adaptive branch-site test of positive selection, revealed that the bat clade showed a high possibility of selection compared to other branches associated with other mammals.
Similar to ACE 2, DPP4 was also widespread across the bat clade. The current study suggested that MERS-CoV can infect many species. The findings of this study are in line with previous studies that reported an enhanced positive selection in bats in ACE2 and DPP4, compared to other mammals, with regards to aminopeptidase N response.
Scientists quantified the similarities between each species and humans associated with ACE2 and DPP4 residues that can bind with coronaviruses. The similarities of ACE2 and DPP4 residues varied within and between mammalian orders. The authors found that most rodents and carnivores’ species were dissimilar to human ACE2.
Domestic cats share most similarities with ACE2 residues that contact SARS-CoV and SARS-CoV-2. Several studies have also indicated that cats can shed both viruses. The current study revealed that pangolin exhibits greater similarity in ACE2 residues to humans compared to most New World monkeys. Additionally, camels were reported to be the closest host for MERS-CoV and were very similar to humans.
ConclusionScientists revealed that evaluation of evolutionary selection and determination of the similarity of host residues that contact viruses are extremely important to identify animals to target viral surveillance. These animals could be the origin of new zoonotic infections. They could also act as secondary reservoir species, which can be infected by humans and also re-infect humans or other species.
Bats and brain worms: how humanity’s environmental impact is giving rise to new infections
As the world’s first case of a parasitic roundworm infecting a human’s brain made headlines this week, infectious diseases experts warned the threat of novel infections is rising.
In a case report written about the Australian patient in the journal Emerging Infectious Disease, doctors who pulled the Ophidascaris robertsi larvae from her brain warned the case highlights the danger of diseases caused by viruses, bacteria, parasites and fungi passing from wildlife to humans, known as zoonotic infections.
“The occasional person developing an odd brain worm from eating greens contaminated with python faeces containing the larvae is unfortunate,” says Rowland Cobbold, the University of Queensland’s associate professor of veterinary science.
“But it’s a rare event, and if it’s treatable, that’s OK.”
What is more concerning, he says, is that about 75% of the novel and emerging infections globally are zoonotic. They often include infections with far greater impact that can lead to millions of deaths, such as the Sars-CoV-2 virus which causes Covid-19 and is believed to have emerged from bats.
“It just comes down to the fact that the human population has never been higher, and we’re all looking for places to live and food to eat and it has an impact on the environment,” Cobbold says. “And so the environment impacts us back.”
It’s an issue Dr Anthony Fauci, the former chief medical adviser to the president of the United States, warned of as he prepared to step down from the role earlier this year. In a perspective written for the New England Journal of Medicine, Fauci said: “There is no reason to believe that the threat of emerging infections will diminish since their underlying causes are present and most likely increasing.”
“The emergence of new infections and the reemergence of old ones are largely the result of human interactions with and encroachment on nature,” he wrote.
“As human societies expand in a progressively interconnected world and the human-animal interface is perturbed, opportunities are created, often aided by climate changes, for unstable infectious agents to emerge, jump species and in some cases adapt to spread among humans.”
There really has to be very careful management of our natural resourcesRowland Cobbold, associate professor
In response to these concerns, the World Health Organization (WHO) has begun holding a series of webinars on the “One Health” approach, which emphasises the importance of different sectors such as public health, veterinary science, social science, urban design, government and environmental science working together in all aspects of society.
But WHO’s director of the department of pandemic and epidemic diseases, physician Dr Sylvie Briand, tells the Guardian this approach “doesn’t happen naturally”.
“It requires effort for each sector to talk to each other to work together,” Briand says.
“It requires sufficient financing to do those joint activities. And it requires, also, a political will to implement interventions.
“Because, for example, the killing of poultry or the killing of minks that has happened during Covid-19 to prevent the spread of a new variant also has a real cost for the economy. So it’s important that governments understand these preventive measures may be costly, but it’s much less costly than to cure [a pandemic].”