A global plan to prevent the next pandemic

Although Covid-19 restrictions are rapidly fading around the world, we are still reeling from the impact of the past three years. More than 6.8 million deaths from Covid-19 have been officially reported, but the true number may be closer to 15 million. There has been immense suffering and social and economic turmoil, and the virus itself still poses a clear and present risk, with one in five Americans reporting ongoing “long COVID” symptoms.

Worse, Covid-19 is far from the last zoonotic disease with the potential to devastate the global population. Innumerable other viruses – many of which remain understudied – have been discovered in animals. Any of them could serve as a source of new human viruses, which often originate from repeat-offender virus families such as coronaviruses, orthomyxoviruses, and filoviruses. When viruses from these families show up in mammals or birds, there is always a risk that they could develop the potential to infect humans. And when that happens, the fact of globalization means that those viruses can spread faster than ever before.

A key challenge, then, is to discover and identify which viruses pose the greatest risks to humans. If we can detect a new human virus in the earliest days of a disease outbreak, we will have a much better chance of implementing the measures needed to prevent another global pandemic. To that end, a recent article in Science proposes setting up an experimental pipeline whereby researchers can test animal viruses for four crucial properties consistent with human infection.

By identifying the viruses that pose the highest risk for zoonosis (transmission across species), we can then rapidly roll out diagnostic panels to detect new human infections. Serology- and polymerase-chain-reaction-based diagnostics are currently the most practical solutions for health-care settings around the world. But they are pathogen-specific, so they are effective only when clinicians and scientists know which pathogens they should be testing for.

An animal virus needs four essential biological properties in order to infect humans: it must use the human version of its cellular entry receptor to gain access to human cells; it must use human intracellular proteins to replicate and exit human cells; it must overcome humans’ innate immune responses; and it must evade pre-existing human adaptive immunity functions such as antibodies and T cells.

Animal viruses that have most of these properties – such as primate arteriviruses – obviously warrant targeting by new diagnostic tools. Such tests can be grouped into regional panels for use in diagnosing unusual or unattributable human illnesses, as well as to monitor healthy populations for virus-surveillance purposes.

The first zoonotic property – an ability to enter human cells – is often the easiest to study, because we can test the surface protein of an animal virus by engineering it onto a reporter virus. (A reporter virus genome lacks genes essential for viral replication, making it safe for research and surveillance purposes.) This method has been shown to demonstrate that some poorly studied tibroviruses from the Rhabdoviridae family can enter human cells, though their multiplication within human cells is uncertain.

They already are. New cases of highly pathogenic avian influenza across the United States and in other parts of the world are a wake-up call. We should always assume that the next pandemic is closer than most people think. - William A. Haseltine, a scientist, biotech entrepreneur, and infectious disease expert, is Chair and President of the global health think tank ACCESS Health International. - Project Syndicate