Although an extensive number of antibiotics are available to combat bacterial diseases, effective treatments for viral diseases are extremely limited. Researchers in the UCLA AIDS Institute conducted a study that suggested that photosensitizing a virus’s membrane covering can inhibit its ability to enter cells. The finding could lead to the development of more potent and less expensive antivirals that can be effective against a number of harmful viruses. They published their findings in the February edition of the Journal of Virology.
The study is a component of ongoing research focused on a compound called LJ001, which is a “broad-spectrum” antiviral that can attack an extensive variety of viruses. The new study takes the research a step further by showing that the process of photosensitization, which enhances a b a biological organism’s sensitivity to certain damaging processes induced by light, applies to more than just LJ001. The researchers note that the new study could result in the development of a cost effective method to make blood products safer, which is particularly important for resource poor countries where deadly viruses run rampant.
The study authors explain that there are two categories of viruses: lipid-enveloped and non-enveloped. Enveloped viruses are surrounded by a membrane, which serves as a mechanism whereby the virus delivers its genome into a host cell; thus, infecting it. Many harmful viruses contain this envelope, noted first author Frederic Vigant, the study’s first author who conducted the research as a postdoctoral researcher in the Department of Microbiology, Immunology and Molecular Genetics (MIMG) at the David Geffen School of Medicine at UCLA. He explained, “The ability of photosensitizers to inactivate many different viruses has been known for decades.” Photosensitizers have the ability to cross-link DNA and RNA, which can irreversibly damage viral genetic material. He explained, “It must have seemed so obvious this was how photosensitizers work, that no one ever looked in detail at the oxidation of the lipids.” He added, “Oxidation of lipids by light, termed photo-oxidation, is also very well known,” he added.
In the study, the researchers determined how photo-oxidation of the viral lipid envelope can serve as a method for compromising the ability of lipid-enveloped viruses to enter cells. In a previous study published in 2010, the investigators described LJ001, which is an antiviral small molecule that is effective against numerous viruses, including HIV-1, influenza A, filoviruses, poxviruses, arenaviruses, bunyaviruses, paramyxoviruses and flaviviruses. These viruses are responsible for some of the world’s deadliest diseases (e.g., AIDS, Nipah virus encephalitis, Ebola hemorrhagic fever, and Rift Valley fever). The researchers note the LJ001 may also be effective against new, yet-to-be discovered enveloped viruses.
Following the 2010 study, the researchers published a study that found that the LJ001 broad-spectrum antiviral, and its more potent second-generation derivatives, could be effective against any lipid-enveloped virus via photosensitization of the envelope. Dr. Lee noted that this was the first time this process was identified and used as an antiviral strategy. He noted that the new study found that this new paradigm for antivirals applies to more than just LJ001. The investigators evaluated another broad-spectrum antiviral compound called dUY11, which was thought to act as a “wedge” by inserting into viral membranes and compacting the lipids; thus, impairing fusion and entry into cells. The researchers explain that this process is unlikely to occur on its own because it is inactive in the dark. It was found to behave as a photosensitizer in all the experiments they performed. As with LJ001 and its derivatives, dUY11 enters the viral membranes, is activated by light, and then alters the lipid composition of the viral coating, resulting in the inability of the virus to fuse with and enter cells. Dr. Vigant explained, “In other words, instead of the compound itself acting as a physical constraint on the membrane, we show that it actually works through photochemical reactions that end up changing the biophysical properties of the virus membrane that make it unable to mediate fusion.”