We did not know about the SARS-CoV-2 virus before it appeared in humans. However, previous experience with other coronaviruses (SARS and MERS) that have entered humans tells us that things like COVID-19 can be dangerous. Coronaviruses are ubiquitous in many species that come into contact with humans, and they have a clear history of adapting themselves to human cells.
Being aware of viruses with similar attributes can help us identify threats to future epidemics. Now, researchers are carrying out the results of large-scale virus investigations and publishing public databases containing hundreds of viruses, all of which assess the risks that viruses pose to humans. Moreover, any viruses we find can be inserted into the framework they developed so that we can quickly understand whether they are threatening.
This work stems from a program called PREDICT funded by the United States Agency for International Development, which is part of an effort to combat zoonotic diseases, which can cross species barriers and infect humans. Overall, the PREDICT project conducted a large-scale investigation of animal viruses, using more than 500,000 individual samples taken from 75,000 species of animals. Among these data, the project identified more than 700 new viruses, and another one has never been found in the animal in which the virus was found.
On its own, understanding the genome sequence of the virus does not tell us much about the risks that the virus poses to humans. We can find out the proteins that the virus encodes, but we are not looking for these proteins and determining whether they make the virus more likely to infect humans. In addition, not only contagion brings risks. If the virus spreads normally in rare animals that avoid humans, the chance of it jumping into us is very small.
These factors abound, and experts have different opinions on the importance of these factors. Therefore, figuring out how to evaluate these new viruses poses a challenge.
To understand what is important, the researchers asked 150 virology and public health experts to consider 50 different potential risk factors, from the host species that carried it to the place where it was found, to its evolution with known viruses relationship. Experts are required to rank the importance of each risk factor, and the PREDICT team will weigh each rating based on the person’s expertise on each issue. (So, for example, the opinion of a virologist may be less involved in issues related to the frequency of interaction between host animals and humans.)
Some important risk factors that have been highly valued are obvious: the frequency of interaction with humans and our livestock, the ability to infect various hosts, and the mode of transmission. However, not every factor is rated as very important, and seven of them are rated as important. But we simply don’t have enough data on most viruses to evaluate them.
The final result is the overflow score, which is the best estimate of the risk of each virus to humans, awkwardly graded on a score of 1 to 155 (this is the degree of result measured when you start from 1-5 with a score of 50 Different, and then throw some of them away). To test its effectiveness, the researchers studied the virus with the highest score. All of the top twelve are known to have infected humans.
SARS-CoV-2 ranks close to the right between the two viruses that have caused multiple outbreaks of hemorrhagic fever in Africa: Lassa and Ebola. It failed to stand out because these other viruses caused multiple outbreaks (SARS-CoV-2 only broke out once, but forget it). We also know more about their normal hosts, although we have not yet determined the species that SARS-CoV-2 was in before it entered humans.
All analyses are available through the Spillover website, which includes a ranked list of all viruses analyzed so far. A quick glance at each risk can be divided into three categories (according to its host, the host’s environment, and the genetics of the virus). The detailed view shows each individual factor that we have enough data to evaluate.
In addition to making data about these new viruses available, Spillover is also a flexible sharing platform. Flexible, because as we learn more about the factors that make viruses a threat to zoonotic diseases, researchers guarantee that they will update the analysis of all viruses in the database. And sharing, because the PREDICT team hopes to add new viruses to the research community in order to rate the viruses found. A risk score with at least six virus characteristics can be created.
Although these many new viruses are a good start, there are still some obvious limitations. First, because it has been tracked in depth, researchers do not need to add influenza viruses to their database. Second, although it represents a lot of work, compared to the estimated 1.7 million viruses that infect mammals and birds, the hundreds of viruses described here are a drop in the bucket. If we really want to avoid the next pandemic, we still have a lot of work to do.
Nevertheless, the project is a worthy start. Compared with the viruses that we already know can make humans leap, several viruses that have not been described before are considered to be more threatening. Obviously, people who conduct research and monitor more carefully have the potential to reap substantial returns, especially when compared to the global costs of the COVID-19 pandemic.
PNAS, 2021. DOI: 10.1073/pnas.2002324118 (about DOI).