A group of bat viruses closely related
to the deadly Middle East respiratory syndrome coronavirus (MERS-CoV)
could be one small mutation away from being capable of spilling over
into human populations and potentially causing the next pandemic.
A recent study published in the journal Nature Communicationsexamined
an understudied group of coronaviruses known as merbecoviruses -- the
same viral subgenus that includes MERS-CoV -- to better understand how
they infect host cells. The research team, which included scientists at
Washington State University, the California Institute of Technology and
the University of North Carolina, found that while most merbecoviruses
appear unlikely to pose a direct threat to people, one subgroup known as
HKU5 possesses concerning traits.
"Merbecoviruses - and HKU5 viruses in particular - really hadn't been
looked at much, but our study shows how these viruses infect cells,"
said Michael Letko, a virologist at WSU's College of Veterinary Medicine
who helped to spearhead the study. "What we also found is HKU5 viruses
may be only a small step away from being able to spill over into
humans."
During the past two decades, scientists have cataloged the genetic
sequences of thousands of viruses in wild animals, but, in most cases,
little is known about whether these viruses pose a threat to humans.
Letko's lab in WSU's Paul G. Allen School for Global Health focuses on
closing that gap and identifying potentially dangerous viruses.
For their most recent study, Letko's team targeted merbecoviruses,
which have received limited attention apart from MERS-CoV, a zoonotic
coronavirus first noted in 2012 that is transmitted from dromedary
camels to humans. It causes severe respiratory disease and has a
mortality rate of approximately 34%.
Like other coronaviruses, merbecovirusesrely on a spike protein to
bind to receptors and invade host cells. Letko's team used virus-like
particles containing only the portion of the spike responsible for
binding to receptors and tested their ability to infect cells in the
lab. While most merbecoviruses appear unlikely to be able to infect
humans, HKU5 viruses - which have been found across Asia, Europe, Africa
and the Middle East - were shown to use a host receptor known as ACE2,
the same used by the more well-known SARS-CoV-2 virus that causes
COVID-19. One small difference: HKU5 viruses, for now, can only use the
ACE2 gene in bats, but do not use the human version nearly as well.
Examining HKU5 viruses found in Asia where their natural host is the Japanese house bat (Pipistrellus abramus),
the researchers demonstrated some mutations in the spike protein that
may allow the viruses to bind to ACE2 receptors in other species,
including humans. Researchers on another study that came out earlier
this year analyzed one HKU5 virus in China that has already been
documented to have jumped into minks, showing there is potential for
these viruses to cross species-barriers.
"These viruses are so closely related to MERS, so we have to be
concerned if they ever infect humans," Letko said. "While there's no
evidence they've crossed into people yet, the potential is there -- and
that makes them worth watching."
The team also used artificial intelligence to explore the viruses.
WSU postdoctoral researcher Victoria Jefferson used a program called
AlphaFold 3 to model how the HKU5 spike protein binds to ACE2 at the
molecular level, which could help provide a better understanding of how
antibodies might block the infection or how the virus could mutate.
Up until this point, such structural analysis required months of lab
work and specialized equipment. With AlphaFold, Jefferson generated
accurate predictions in minutes. The results matched those recently
documented by a research team that used traditional approaches.
Letko noted the study and its methods could be used for future
research projects and aid in the development of new vaccines and
treatments.
The research was funded through a research project grant from the
National Institutes of Health. Jefferson's work was supported by an NIH
T32 training grant.
Journal Reference:
- Nicholas J. Catanzaro, Ziyan Wu, Chengcheng Fan, Victoria Jefferson,
Anfal Abdelgadir, Alexandra Schäfer, Boyd L. Yount, Pamela J.
Bjorkman, Ralph Baric, Michael Letko. ACE2 from Pipistrellus abramus bats is a receptor for HKU5 coronaviruses. Nature Communications, 2025; 16 (1) DOI: 10.1038/s41467-025-60286-3
Courtesy:
Washington State University. "Scientists warn of bat virus just one
mutation from infecting humans." ScienceDaily. ScienceDaily, 12 June
2025. <www.sciencedaily.com/releases/2025/06/250612081312.htm>.