The findings have
been reported by researchers from the University of Washington School of
Medicine, USA. The research team is optimistic that
this type of lab-based research could lead to the development of new therapies
The study findings have been published in Nature Structural & Molecular Biology
The study was
jointly led by Dr. David Veesler, PhD and Dr. Christopher C. Broder, PhD. Dr.
Veesler is an Assistant Professor in the Department of Biochemistry at the
University of Washington School of Medicine in Seattle, while Dr. Broder is a
Professor and Chair in the Department of Microbiology and Immunology at the Uniformed
Services University, Bethesda, MD, USA.
The lead authors of
the paper were Ha V. Dang of the University of Washington and Yee-Peng Chan of
the Uniformed Services University. Other collaborators included scientists from
the Sealy Institute for Vaccine Sciences at the University of Texas Medical
Branch, Galveston, TX, USA.
Epidemiology of Nipah and Hendra Viruses
Nipah and Hendra are RNA
(ribonucleic acid) viruses belonging to the family Paramyxoviridae
Other paramyxoviruses include measles
, parainfluenza, and Newcastle disease viruses,
as well as a respiratory syncytial virus
Nipah and Hendra viruses are spread by infected fruit
bats, also known as flying foxes.
Both the Nipah virus and Hendra virus cause
severe respiratory infections and brain inflammation. Case fatality rates can
range anywhere between 50 percent and 100 percent. Currently, there are no
licensed vaccines or drugs for treating these viral diseases. The mainstay of
prevention involves maintaining a healthy livestock and wildlife management for
preventing animal to human transmission of these viruses.
Outbreaks of Nipah and Hendra Viruses
The first outbreak of Nipah occurred
in Malaysia in 1998, where the virus was transmitted from fruit bats to pigs
and then to humans. Subsequent outbreaks have occurred in Singapore, India, and
Bangladesh. The Singapore outbreak occurred due to the spread of the virus from the initial
Malaysian outbreak to Singapore.
In the outbreaks that occurred in
India and Bangladesh,
the infection spread to humans by drinking palm sap
that had become infected with the virus from fruit bats. In India, Nipah
have been reported from West Bengal and Kerala, while in
Bangladesh, the virus has become endemic and seasonal outbreaks occur almost
Hendra virus outbreaks have been
reported from Australia, where horses have fallen ill due to consumption of
food and water contaminated by fruit bats. Subsequently, the people associated
with the horses, including trainers, owners and veterinarians, also became infected with the virus
due to close contact with the sick horses.
Presence of Nipah and Hendra virus
antibodies among humans and fruit bats in Africa indicates that these viruses
are circulating in this continent, although no human cases have so far been
detected. Therefore, the occurrence of Nipah and Hendra outbreaks in Africa in
the future is a real possibility. Importantly, over 2 billion people across the
globe live in areas where Nipah and Hendra outbreaks can potentially occur.
Mechanism of Infection by Nipah and Hendra
enveloped viruses that have spike-like surface projections made-up of glycoproteins,
of which there are two major types. One type helps in viral attachment, while
the other helps infusion to the host cell surface. With concerted efforts by
the attachment and fusion glycoproteins, a tunnel-like pore is created at the
virus-cell interface, through which the viral RNA is injected into the host
cells to initiate a round of infection.
As opposed to many
other paramyxoviruses, the host-range of Nipah and Hendra viruses is much
broader, allowing them to infect a large variety of mammalian species, which
makes them very dangerous. However, the body's humoral immune response,
mediated by antibodies, keeps these viruses in check by blocking
their attachment to the host cells, thereby preventing
Major Findings of the Study
This study is based
on previous studies, which showed that specific antibodies could block the
attachment of Nipah and Hendra viruses to host cells. Importantly, one of these
antibodies was capable of protecting infected animals even after several days
In this study, the
researchers discovered a specific monoclonal antibody from mice and humanized
it so that it could be administered to humans. This humanized monoclonal
antibody was highly potent and could neutralize both Nipah and Hendra viruses.
Mechanism of Action of the New Monoclonal
The mechanism of
action of the newly discovered monoclonal antibody was elucidated using the
latest biochemical and cellular techniques, as well as
molecular imaging using cryogenic electron microscopy
state-of-the-art techniques revealed that the monoclonal antibody recognizes
and binds to a specific region of the viral fusion machinery prior to the fusion of the viruses to host cells.
Both Nipah and
Hendra viruses possess the same epitope on their surface, which functions as
the target site for attachment of antibodies to bring about viral
neutralization. This sharing of the same epitope explains why the same antibody
is capable of conferring protection against both viruses. Binding of the
monoclonal antibody to the epitope blocks membrane fusion, preventing injection
of the viral RNA into the host cells, thereby halting the infection process.
Based on the
current findings, the researchers are optimistic that combining various
antiviral monoclonal antibodies having different specificities for distinct
targets on Nipah and Hendra viruses, could offer enhanced therapeutic benefits
for infected individuals.
The study was
funded by multiple organizations and funding agencies, including the
NIH/National Institute of Allergy and Infectious Diseases, the NIH/National
Institute of General Medical Sciences, the Burroughs Wellcome Fund, the
Netherlands Organization for Scientific Research, the European Molecular
Biology Organization, and the Pew Charitable Trusts. Reference :
- An Antibody against the F Glycoprotein Inhibits Nipah and Hendra Virus Infections - (https://doi.org/10.1038/s41594-019-0308-9)