Now, in the midst of this ongoing Covid-19 pandemic, we can conclude that the vaccine development has been faster than anyone ever thought possible. But still, when this is over, the losses of lives and means will have been major. Possibly, this is not the last pandemic that we will experience, so how can we be better prepared for the next one? We need to think outside the box, says Prof. Cho, Nanyang technological university in Singapore. His suggested approach is broad-spectrum antiviral targeting.
- As soon as a virus outbreak are over, people essentially stop thinking about it and stop investing resources, Prof. Cho says. This is, for example, what happened both after the Zika outbreak and the SARS outbreak. Now we are in an ongoing Covid-19 pandemic and vaccines are being developed to prevent it from spreading. But, even if the vaccine development has been unbelievably fast, lives will have been lost waiting for vaccines to reach the market, Prof. Cho states. Therefore, not even knowing what the next pandemic is going to be, we need to be prepared for the next one, he says.
To address this issue, Prof. Cho and his team decided to think outside the box and test something new. His background is in material science, and from there, he moved into gastroenterology where he studied an HCV drug screening platform. One of the main sensing technologies that he used to develop this drug-screening platform was QCM-D, Quartz Crystal Microbalance with Dissipation monitoring.
- What we decided to do was to use an approach different from traditional virology and instead look at the virus particles as a material, Prof Cho explains. We wanted to identify the common weak spot of viral particle, the Achilles heel. The common denominator is the viral envelope, so the question was if we could develop a method that would target those envelopes? If we could effectively and selectively target the viral envelopes, then we would have a broad-spectrum antiviral treatment, addressing not just a single virus but several ones, Prof. Cho explains.
- If we can target the lipid envelope, we can prevent viral infection, Prof. Cho says. This is how we coined the LEAD concept - Lipid Envelope Antiviral Disruption, which we have developed as a next-generation antiviral technology.
- We demonstrated the LEAD- concept using a model system based on a mosquito borne virus, an RNA virus, which all have lipid envelopes. One of the drug screening platforms we used was QCM-D.
- The origin of the LEAD-method discovery goes back to a project on the Hepatitis C virus, where we were using the so-called AH peptide, Prof. Cho explains. In 2004, we demonstrated that this AH peptide has a very interesting behavior when it interacts with lipid membranes. What we discovered was that when an assembly of lipid vesicles of a given size, e.g., 30, 50 or 100 nm, sitting on a surface are exposed to the AH peptide, the peptide does not only bind to the lipid surface, which we expected. Instead, what we discovered was that the AH peptide binds to the lipid vesicles, and then the vesicles start breaking to make a bilayer. This binding and rupture process can be followed directly with QCM-D technology, Prof. Cho explains.
- At the time of this study, I didn’t correlate the model system with artificial virus particles, but later, I started to wonder whether the AH-induced vesicle rupture depends on vesicle size. To explore this hypothesis, we made different size populations of artificial vesicles to represent different lipid envelope virus size populations, Prof. Cho says. The study showed that the rupturing efficiency indeed is a function of the vesicle size.
- Then, we directly correlated with in vitro virus assays of two different model systems, Hepatitis C which has a lipid envelope of 50 nm in size, and vaccinia virus, with an envelope size of 360 nm. The LEAD-concept works on the former but not on the latter, Prof. Cho says.
- The LEAD-strategy works against a wide range of viruses that are of importance to clinical medicine and biodefence, Prof. Cho says. We have now shown that the LEAD therapy inhibits ZIKV infection in mice. And you can expand to unknown viruses with physical characteristics similar to those of Zika, i.e., which have a lipid envelope and below 150 nm in size.
Learn more about the LEAD-strategy in this webinar, where Prof. Cho describes the different studies and platform designs in more detail, and how he and his team approaches the challenge to prepare for the next pandemic.
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