August 17, 2022 How zombie attacks could help fight the COVID-19 virus Written By: Jason Daley Departments: Chemical & Biological Engineering Focus Areas: Engineering Healthcare In a July 2022 opinion piece in Scientific American, Vilas Distinguished Achievement Professor in chemical and biological engineering John Yin discusses the potential for using zombie viral particles to reduce the severity of COVID-19 and other viral diseases. John Yin Yin has studied these zombie particles, also known as defective interfering particles, for several years. Normal viruses hijack cells, using the machinery inside them to replicate and spread to more cells. However, virus replication is messy—besides creating full copies of their genomes, viruses also produce lots of non-infectious particles. “It turns out the machinery that copies genomes in viruses can be quite error-prone,” says Yin. “It not only makes single-typo variants, like Omicron or Delta, but you have mutations that are much, much more severe that may skip one or more genes.” That means the virus produces variations that might have a genome only a half, third or even a tenth the size of a normal virus genome. When these viral genomes are delivered to a cell, they appear dead and unable to replicate. However, if these genomes are delivered to a cell with a fully functional virus, they can co-opt the replication machinery of the active virus. “They can grow, then, at the expense of the normal virus,” says Yin. “And that’s interesting, because that might be a way that they could make infections less severe than they might otherwise be.” Recent research suggests that’s possible. In some studies, it appears zombie genomes can trigger a protective immune response, leading to less severe infections. In other cases, the zombies appear to prolong or make disease worse. “The simplest way to interpret it is these particles interfere with normal virus growth and normal virus growth can cause severe disease,” says Yin. “So maybe when these guys are present at high levels, it might tamp down virus growth and the severity of the disease. But I think it’s very plausible that they also could act in the opposite direction, and that when they’re present, they might make this disease more severe.” Understanding these mechanisms and the way the zombies interact or interfere with viruses, Yin says, could help in the development of vaccines with broad protection against various viruses, including influenza and coronaviruses. “There’s some very preliminary data that’s been published in the literature by others that suggests that such a zombie virus might be present in COVID samples,” says Yin. “So this is something we’re also pushing forward to study.” Yin and his team received National Science Foundation grants to study COVID-19 and zombie viruses early in the pandemic. Now they are examining data that many other researchers simply ignore: The researchers are seeking datasets of COVID genomes that may contain these partial zombie genomes so they can sequence and study them. Eventually, it may be possible to identify zombie particles associated with severe disease or zombies that lead to milder cases and help develop engineered zombie particles that provide protection or immunity.