LSTM and Imperial College Researchers design new anti-influenza drugs

January 25, 2019

Researchers at LSTM and Imperial College London have designed drugs which could help combat any potential new flu pandemic, by targeting the receptors of the cells by which the virus gains entry to the human body.

In a paper published today(link is external) in the Journal of Immunology the team, led by LSTM's Professor Richard Pleass, show that by engineering a part of an antibody they can target the viral proteins that allow flu to mutate and become so deadly to humans.

Last year marked the centenary of the 1918 influenza pandemic that claimed nearly 100 million lives worldwide, thus becoming the deadliest disease outbreak in recorded history. Global annual influenza outbreaks account for 300,000-650,000 respiratory deaths, mostly in children and the elderly.

Professor Pleass explained: "Influenza vaccines have limited public health impact during pandemics, and current influenza vaccines are less efficacious than vaccines for many other infectious diseases. This is because influenza viruses that circulate in human and animal populations mutate two key viral surface proteins, haemagglutinin (HA) and neuraminidase (NA), thus allowing them to escape from protective antibodies produced through natural infection or vaccination"

Both HA and NA target a sugar called sialic acid, that is found in abundance on the receptors of cells lining the mammalian respiratory tract, which the virus uses to gain entry into the body. The sialic acid-binding contacts on HA and NA do not mutate readily, otherwise the virus would not be able to infect human cells.

The team has engineered antibody Fc fragments with enhanced sialic acid that target these conserved parts of both HA and NA, binding influenza viruses and thus blocking their interactions with human cells.

By targeting sialic acid, these engineered biologicals may also be useful in the control of other pathogens, such as group B streptococci, Streptococcus pneumoniae, Mycoplasma genitalium, and Newcastle Disease Virus.

"Better anti-influenza therapeutics are urgently needed." Continued Professor Pleass: "The transfer of antibodies from people recovering from influenza during the 1918 and 2009 pandemics reduced mortality from influenza by 50% and 26% respectively. However, to be useful, these antibody medicines (also called FLU-IVIG) need to be manufactured in advance of future epidemics, which is obviously problematic as there may be modest or little neutralising activity against newly emerging strains. Therefore, combinations of existing medicines, including FLU-IVIG, with sialic acid blockers could increase their efficacy while future-proofing against the next pandemic."

Professor Sara Marshall, Head of Clinical and Physiological Sciences at the Wellcome Trust, who provided funding for this work, said: "This is a fascinating project, and one which could have really far-reaching impact not only for influenza but as a platform technology to develop new medicines for many other diseases that are currently treated by antibodies."

The technology described is available for licensing.
-end-


Liverpool School of Tropical Medicine

Related Influenza Articles from Brightsurf:

Predicting influenza epidemics
Researchers at Linköping University, Sweden, have developed a unique method to predict influenza epidemics by combining several sources of data.

Common cold combats influenza
As the flu season approaches, a strained public health system may have a surprising ally -- the common cold virus.

Scent-sensing cells have a better way to fight influenza
Smell receptors that line the nose get hit by Influenza B just like other cells, but they are able to clear the infection without dying.

New antivirals for influenza and Zika
Leuven researchers have deployed synthetic amyloids to trigger protein misfolding as a strategy to combat the influenza A and Zika virus.

Assessment of deaths from COVID-19, seasonal influenza
Publicly available data were used to analyze the number of deaths from seasonal influenza deaths compared with deaths from COVID-19.

Obesity promotes virulence of influenza
Obesity promotes the virulence of the influenza virus, according to a study conducted in mice published in mBio, an open-access journal of the American Society for Microbiology.

Influenza: combating bacterial superinfection with the help of the microbiota
Frenc researchers and from Brazilian (Belo Horizonte), Scottish (Glasgow) and Danish (Copenhagen) laboratories have shown for the first time in mice that perturbation of the gut microbiota caused by the influenza virus favours secondary bacterial superinfection.

Chemists unveil the structure of an influenza B protein
MIT chemists have discovered the structure of an influenza B protein called BM2, a finding that could help researchers design drugs that block the protein and help prevent the virus from spreading.

How proteins help influenza A bind and slice its way to cells
Researchers have provided new insight on how two proteins help influenza A virus particles fight their way to human cells.

Eating elderberries can help minimize influenza symptoms
Conducted by Professor Fariba Deghani, Dr. Golnoosh Torabian and Dr.

Read More: Influenza News and Influenza Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.