A research team from the Institute of Integrative Systems Biology (I2SysBio), located in the scientific-academic area of the University of Valencia Science Park (PCUV), claims that the proteins responsible for mediating the entry of animal viruses into human cells and infecting them also do so in human cells, so that the barriers to interspecies transmission are lower than previously thought. In the journal Nature Microbiology, they explain that they have constructed safe viral prototypes with RNA remnants of 102 enveloped viruses from 14 different families and tested their infectivity with more than 5,000 combinations
"Just because a virus enters our cells does not automatically mean that it causes disease. For that to happen, it requires a combination of additional factors that we are still investigating. Our work is an important step towards identifying which viruses pose a greater risk to humans and how we can better prepare for them", explains Rafael Sanjuán, researcher at the Institute for Integrative Systems Biology (I2SysBio) and professor of Genetics at the Universitat de València.
To understand the infectious capacity of certain viruses, they have constructed pseudoviruses, a kind of safe imitation of real viruses, using parts of them, such as their RBP protein, which is key to their entry into cells. These were inoculated into human cells. They also explored the role of proteases and carbohydrates in the infection process in cells.
"This allowed us to study whether certain animal viruses, which had never been analysed in detail before, can enter human cells. The results showed that many animal viruses have this capacity. This means that we are potentially exposed to a large number of viruses", adds Sanjuán, who has published more than 100 research papers on viruses and evolution.
Research cannot predict which viruses could cause the next pandemic: "It is very difficult, because there are many factors at play, such as ecology, genetics, the immune system and evolution. In addition, it is estimated that there are tens of thousands of viruses that infect mammals, and many of them could infect humans", Rafael Sanjuán, researcher at I2SysBio
This research, ‘Experimental Virology for Assessing Disease Emergence Risks’ (EVADER), is part of a project on wildlife virus threats that received 2.43 million euros from the European Research Council in 2021 in Advanced Grants, the largest grants awarded by Europe's leading research organisation. The significance of this research lies in the fact that many diseases such as AIDS, influenza or COVID-19 originated from jumping from animals to humans. Sanjuán has obtained funding from the ERC almost continuously for the past 15 years.
This process - viruses jumping from animals to humans, or zoonoses - is more common in enveloped RNA viruses, as they have a strong ability to adapt and spread between species and cause pandemics. Research cannot predict which viruses might cause the next pandemic: "It is very difficult, because there are many factors at play, such as ecology, genetics, the immune system and evolution. In addition, it is estimated that there are tens of thousands of viruses that infect mammals, and many of them could infect humans", explains Sanjuán, who points out that thanks to metagenomics, many viruses are currently known, but only from their genetic material, as they have never been cultivated or studied directly in the laboratory.
New human viruses causing diseases originating in animals are a growing concern. Their emergence is also a poorly understood process. The COVID-19 pandemic demonstrated that combating wildlife viruses is an urgent challenge, and the scientific community has been launching massive sequencing programmes to characterise wildlife viruses. This new research reveals repeatable evolutionary pathways that could improve outbreak predictions and increase the feasibility of using broad-range antiviral therapies to combat emerging viruses.
Source: University of Valencia
Dufloo, J., Andreu-Moreno, I., Moreno-García, J. et al. Receptor-binding proteins from animal viruses are broadly compatible with human cell entry factors. Nat Microbiol (2025). https://doi.org/10.1038/s41564-024-01879-4