Innovative peptide-based hydrogel therapy for virus prevention

Innovative peptide-based hydrogel therapy for virus prevention

Vaccines remain the gold standard for protection against dangerous pathogens, but their development requires a lot of time and enormous resources. Rapidly mutating viruses such as SARS-CoV-2 can weaken their effectiveness and even make them unnecessary.

To address these gaps, a multi-university team led by Vivek Kumar of the New Jersey Institute of Technology is developing a hydrogel therapy that acts as a first line of defense against viruses and other biological threats. The peptides that make up this gel prevent viruses such as SARS-CoV-2, which causes COVID-19, from attaching to and entering cells. To do this, they bind to a specific receptor of the invading pathogen and at the same time aggregate to form a multi-layered “molecular mask” that dampens its effect.

Over the course of their research, the team found that the molecular mask alone prevented infections. The potential advantage of this new technology is its ability to combat various pathogens and disease mutations.

Protecting people in the early stages of an outbreak is important. Our new mechanism could also help frontline first responders, military personnel encountering novel pathogens, people in remote, underserved areas, and people unable to receive vaccinations.”

Vivek Kumar, Associate Professor of Biomedical Engineering, New Jersey Institute of Technology

The short-term goal is to create a nasal spray against airborne infections.

In a study recently published in the journalNature communicationThe team described how the mask binds to its target in a non-specific manner. It consists of computationally designed peptides (amino acid chains that form proteins) that self-assemble into nanoscale fibrous hydrogels. In comparison, the antibodies produced by vaccines target specific receptors, like the mRNA vaccines developed during the pandemic, which bind to specific proteins on the SARS-CoV-2 spike.

The team's discovery arose from research early in the pandemic on new approaches to prevent the virus from entering cells. The initial design, which included peptides targeting the SARS-CoV-2 spike, addressed highly specific domains. However, the non-specific peptide gels they also developed formed a multi-layered fiber on the virus. The group has postulated that the negative charges in the fibers interact with differently charged proteins on the virus surface, masking them and preventing them from interacting with native cells.

Regarding the non-specific protein mask, Kumar noted, "It forms a larger structure and binds better than a single molecule. Although it does not have high specificity, it can self-assemble and stay on the target for a longer time and form a fiber." Sticker on the surface that acts like molecular Velcro.”

He added: "The goal would be a topical agent that binds to the virus. In the case of SARS-CoV-2, we would spray it into the nose, which is a major site of infection, perhaps even prophylactically."

The team first tested the fibers against a range of viruses using computer simulations using powerful NVIDIA graphics cards, which are often used in competitive gaming. They later conducted successful safety tests on mice and rats using injections and nasal sprays, said Joseph Dodd-o, a Ph.D. student in Kumar's lab, who conducted much of the research on the therapy along with Abhishek Roy, also a graduate student. Student. The therapy inhibited the alpha and omicron variants of SARS-CoV-2 in vitro and lasted for a day without harming the animals in the in vivo tests.

Kumar has developed hydrogels for a range of therapeutic applications. Its delivery mechanism is customizable and consists of Lego-like peptide strands with a bioactive agent at one end that can survive for weeks and even months in the body where other biomaterials are rapidly broken down. Its self-organizing bonds are designed to be stronger than the body's dispersive forces; It forms stable fibers, without signs of inflammation.

The hydrogel is designed to trigger different biological responses depending on the payload attached. Kumar's lab has published research on applications ranging from therapies to promote or prevent the formation of new blood vessel networks to reducing inflammation and fighting microbes.

“In this case, we use electrical charges that interact with the pathogen to destroy it,” Kumar said. "We're still trying to figure out how the fibers interact: Is this a mechanical mode of action? Drug-resistant pathogens mutate around biochemical modulators, but are they less likely to mutate around a mechanical spear? By understanding this fundamental interaction, that's what we want to do." Find out how to use it against various diseases.

In new studies, the laboratory is testing therapy against drug-resistant bacteria and fungi.

Team members bring a diverse range of expertise: computer design at the University of Illinois Chicago; bioanalytical skills at Georgia Tech and Baylor School of Medicine; studied virology at Rutgers University; and platform, analysis and assay experience at NJIT.

Her research is funded by the National Institutes of Health, the US National Science Foundation and the New Jersey Economic Development Authority.

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