Scientists at Nanyang Technological University, Singapore (NTU Singapore) have engineered an antiviral peptide that exploits the Zika virus at its Achilles' heel – the viral membrane – hence stopping the virus from causing severe infections.
When administered in Zika-infected mice in the lab, the engineered peptide drug reduced disease symptoms and the number of deaths. Importantly, the peptide was able to cross the nearly impenetrable blood-brain barrier to tackle viral infection in mouse brains and protect against Zika injury, a critical feature since Zika targets the brain and central nervous system.
How the engineered antiviral peptide works
In 2004, Assoc Prof Cho developed the first antiviral peptide that works against viral membranes in laboratory tests. Since then, NTU scientists have studied how antiviral peptides can create pores that form in membranes made up of two layers of lipids (a component of fats).
"The peptide differentiates between Zika viral membranes and mammalian cell membranes because the virus particles are much smaller and more curved, while the mammalian cells are larger and flatter Like how to pin pricks a balloon, the peptide pricks a hole in the viral membrane. Prick enough holes, and the virus will be ruptured, "said Assoc Prof. Cho.
"The exciting antiviral results validate the potential of this innovative therapeutic strategy and are further enhanced by the engineered peptide's ability to cross the blood-brain barrier," said Jeffrey S. Glenn.
Fresh approach in targeting viruses
In general, most antiviral drugs target the replication process of viruses. However, viruses often mutate rapidly and antiviral drugs that target viral replication can become obsolete. Attacking the physical structure of enveloped viruses is a new approach to developing antiviral drugs. It offers promise for the peptide to be effective even if the Zika virus attempts to mutate.
Assoc Prof. Cho said, "There are instances where a virus mutation can lead to an epidemic in a short time, leaving communities unprepared." By targeting the lipid membrane of virus particles, scientists can devise more robust and effective ways to stop viruses. "
Laboratory tests in this study confirm this potential and in future, the research team intends to study the effects of the peptide on diseases caused by these other viruses in greater detail. The team will conduct trials in larger animals, and later will plan to initiate human clinical trials, eleven relevant preclinical studies are completed and regulatory approvals obtained.
"This work represents a paradigm-changing breakthrough in the field of antiviral drug design," commented Professor William C. Wimley, an antimicrobial peptide expert from Tulane University in the United States, who is not part of the study.
"It shows how the viral envelope, a novel target in antiviral drug design, can be specifically targeted by a peptide. It also shows that a peptide targeting the viral envelope can effectively inhibit virus in the body, and even in the brain, an organ That excludes many therapeutics Given the vast potential of peptides as antibacterial and antifungal agents, this may be a game-changing discovery that will be broadly applicable to the design of anti-infective drugs against many kinds of pathogens. "
Related antiviral technologies have been licensed from NTU Singapore to a local spin-off company, TSG Therapeutics Pte. Ltd., as part of plans to spur clinical translation. Assoc Prof Cho is co-founder of TSG Therapeutics.