Peptide exploits the Achilles heel of Zika virus

Scientists from the Nanyang Technological University of Singapore (NTU Singapore) have developed an antiviral peptide that exploits the Zika virus at the Achilles' heel – the viral membrane – thus preventing the virus from causing serious infections.

This new method of viral membrane attack focuses on direct stopping of Zika virus particles rather than preventing the replication of new particles and potentially acting against a wide range of membrane viruses.

When it was administered to the laboratory to Zika-infected mice, the modified peptide drug (composed of amino acids) reduced the symptoms of the disease and the number of deaths. It is important to note that the peptide has been able to cross the almost impenetrable blood-brain barrier to fight viral infection in the mouse brain and protect against Zika virus damage, an essential feature of the fact that Zika targets the brain and the central nervous system.

The research team led by Nam-Joon Cho, Associate Professor at NTU Singapore, published his findings in a peer-reviewed journal Nature Materials October 22, 2018.

The study, carried out in collaboration with the Federal University of Minas Gerais (UFMG) in Brazil and the University of Ghent in Belgium, lasted six years and combined material engineering, development of engineering and design. antivirals and pharmacology.

"There is currently no vaccine against the Zika virus, while the available drugs only relieve symptoms such as fever and pain," said Associate Professor Cho of the Faculty of Materials Science and Medicine. the engineering of the NTU University. "This newly created peptide is very promising to become a future antiviral drug that can directly affect viral infections in the brain."

The Zika virus is transmitted by Aedes mosquitoes and infections during pregnancy are related to congenital anomalies such as microcephaly, a condition in which a baby is born with an abnormally small head and brain. The World Health Organization said that Zika's disease was an international emergency in 2016 and that it remains a major threat globally.

How does the antiviral peptide work?

In 2004, Associate Professor Cho developed the first antiviral peptide that acts against viral membranes during laboratory tests. Since then, NTU scientists have been studying how antiviral peptides can create pores that form in membranes composed of two layers of lipids (a component of fats).

Over the years, the team has been studying peptide interactions with lipid membranes and developing new, more potent peptides with improved pharmacological properties. These findings led them to test a particularly promising peptide in mice infected with Zika virus and also showed that it had broken other similarly sized enveloped viruses in the laboratory, such as dengue and chikungunya. .

"The peptide differentiates Zika viral membranes from mammalian cell membranes because the viral particles are much smaller and more curved, while the mammalian cells are larger and flatter." As a pin stings a balloon, the peptide pierces a hole in the viral membrane, prick enough holes and the virus will be broken, "said Associate Professor Cho.

Laboratory tests showed that when the peptide was administered, 10 out of 12 infected mice survived. In comparison, all mice in the control group died one week after infection. In addition, the therapeutic concentrations of the peptide were able to cross the blood-brain barrier, which allowed it to inhibit the viral infection in the brain.

"The excellent antiviral results confirm the potential of this innovative therapeutic strategy and are further enhanced by the ability of the modified peptide to cross the blood-brain barrier," said Jeffrey S. Glenn, professor of medicine, microbiology, and microbiology. immunology at Stanford University. is not part of the study. Professor Glenn is also a former member of the FDA's Antiviral Drugs Advisory Committee in the United States.

New approach to target viruses

In general, most antiviral drugs target the process of virus replication. However, viruses often mutate rapidly and antiviral drugs that target viral replication may become obsolete. S attacking the physical structure of enveloped viruses is a new approach to the development of antiviral drugs. It offers the promise that the peptide will be effective even if the Zika virus tries to mutate.

Associate Professor Cho said, "In some cases, a mutation of the virus can lead to an epidemic in a short time, leaving communities unprepared." By targeting the lipid membrane of viral particles, scientists can design more robust ways and effective in stopping viruses. "

Zika virus belongs to the Flaviviridae family and is related to other mosquito-borne viruses, such as dengue, chikungunya and yellow fever. Since all flaviviruses have viral particles about 40 to 55 nanometers in diameter and are enveloped in a lipid membrane, the peptide developed by scientists at NTU Singapore can also fight against these viruses.

The laboratory tests of this study confirm this potential and the research team intends to study in more detail the effects of the peptide on the diseases caused by these other viruses. The team will also conduct trials on larger animals and then consider initiating human clinical trials once the relevant preclinical studies are completed and regulatory approvals are obtained.

"This work represents a breakthrough in the field of antiviral drug design," commented Professor William C. Wimley, an expert on antimicrobial peptides at Tulane University in the United States, who was not part of the research team. # 39; study.

"It shows how the viral envelope, a new target in the design of antiviral drugs, can be specifically targeted by a peptide.It also shows that a peptide targeting the viral envelope can effectively inhibit the virus." in the body, and even in the brain, in an organ considering the vast potential of peptides as antibacterial and antifungal agents, it could be a discovery that will change the deal and that will be broadly applicable to the design of anti-infective drugs against many classes of pathogens. "

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More information:
Joshua A. Jackman et al. Therapeutic treatment of Zika virus infection with the aid of an antiviral peptide penetrating into the brain, Nature Materials (2018). DOI: 10.1038 / s41563-018-0194-2