A team of researchers from the University of California, Los Angeles (UCLA) has discovered a new class of antiviral agents that could help fight emerging infectious diseases. The most promising of these agents are cyclic dinucleotide (CDN) STING agonists, which have the potential not only to combat viral infections but also to activate the immune system to fight cancer. Lead author Vaithi Arumugaswami, an associate professor in UCLA's Department of Molecular and medical pharmacology, says, "Our findings could open up new avenues for developing treatments that are more effective and much less toxic than existing antiviral agents."
The UCLA Department of Molecular and Medical Pharmacology, led by Gustavo Garcia Jr., recently conducted a study that uncovered potential broadspectrum antiviral drugs that could target various RNA virus families, which remain an imminent threat to future pandemics. Through testing a library of innate immune agonists that act on pathogen recognition receptors, the team discovered several agents with promising results, one of which displayed potent antiviral activity against members of the RNA viral families.
The SARS-CoV-2 pandemic has highlighted the fragility of human society in the face of a large-scale outbreak of novel pathogens. With the continuous mutation of its RNA genome, arboviruses such as Chikungunya virus (CHIKV), Dengue virus, West Nile virus, and Zika virus are potential candidates for causing the next pandemic. To protect against this possibility, it is critical to develop effective treatments for these viruses before any further pandemics arise.
In their new study published in Cell Reports Medicine, researchers found that cyclic dinucleotide (CDN) STING agonists were the most potent and broad-spectrum antiviral agents. According to senior author Vaithi Arumugaswami, Associate Professor in the UCLA Department of Molecular and Medical Pharmacology, "these agents also hold promise in triggering an immune defense against cancer. Furthermore, a single dose treatment of STING agonist cAIMP effectively prevents and mitigates the debilitating viral arthritis caused by the Chikungunya virus in a mouse model, providing a very promising treatment modality for Chikungunya virus-affected individuals who suffer from viral arthritis years and decades after initial infection."
The study conducted by Garcia concluded that STING agonists have a broad spectrum of antiviral properties capable of inhibiting multiple arthropod-borne and respiratory viruses, including SARS-CoV-2 and Enterovirus D68, in cell culture models. Garcia further commented that the next step is to combine these broad-spectrum antivirals with existing antivirals to be ready for future respiratory and arboviral disease outbreaks.
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