Summary of A New Frontier in the Fight Against Emerging Diseases:
Researchers at the University of California, Los Angeles (UCLA) have discovered several potential broad-spectrum antiviral agents that can target various RNA virus families, including those that threaten future pandemics. The most promising agents were cyclic dinucleotide (CDN) STING agonists, which exhibit potent antiviral activity against arthropod-borne and respiratory viruses, including COVID-19. One STING agonist, cAIMP, even prevented and alleviated viral arthritis caused by the Chikungunya virus in a mouse model. The researchers aim to develop these and existing antivirals to prepare for future disease outbreaks.
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Researchers Discover Potential Broad-Spectrum Antivirals Against Future Pandemics
A recent study led by Gustavo Garcia Jr. in the University of California, Los Angeles (UCLA) Department of Molecular and Medical Pharmacology has identified potential broad-spectrum antiviral agents that could target various RNA virus families, including those causing future pandemics. The study tested a library of innate immune agonists that targeted pathogen recognition receptors and found several therapeutic potential agents. The most effective among these was the cyclic dinucleotide (CDN) STING agonists, which can potentially enhance cancer immunotherapy while showing potency against the Chikungunya (CHIKV), respiratory viruses, and the SARS-CoV-2 virus.
STING agonists show promise against viral arthritis
According to the study, a single dose of the STING agonist named cAIMP displayed efficiency in averting viral arthritis induced by CHIKV in a mouse model, highlighting its therapeutic potential. The researchers hope to develop these antivirals in conjunction with existing ones, thoroughly equipped for future respiratory and arboviral disease outbreaks. They assert that the vulnerability of human society to large-scale attacks of emerging pathogens has been revealed by the ongoing SARS-CoV-2 pandemic, which has claimed nearly seven million lives globally since it began. Recent epidemics, global climate change, and the continuously evolving nature of the RNA genome indicate that arboviruses are prime candidates to cause pandemics. These include CHIKV, Dengue virus, West Nile virus, and Zika virus, among others.
Towards an effective broad-spectrum treatment against arboviruses
The STING agonists were the most potent, exhibiting broad-spectrum antiviral activity against arthropod-borne and respiratory viruses, including SARS-CoV-2 and Enterovirus D68. Given their already-demonstrated epidemic potential, the study reveals that several antivirals inhibited these arboviruses to varying degrees. According to the study’s senior author, Vaithi Arumugaswami, Associate Professor in the UCLA Department of Molecular and Medical Pharmacology, the STING agonists also had therapeutic potential in triggering immune defenses against cancer. Given their already-demonstrated epidemic potential, the authors stress the need to find effective broad-spectrum treatments against these viruses.
STING agonists reverse the harmful effects of CHIKV-induced dysregulation
Senior author Arunachalam Ramaiah, Senior Scientist in the City of Milwaukee Health Department, explains that CHIKV contributes to transcriptional and chemical imbalances in infected skin cells compared to West Nile Virus and ZIKA Virus, reflecting a possible difference in the viral-mediated injury (disease pathogenesis) mechanisms by viruses belonging to different families, despite all being mosquito-borne viruses. The study of transcriptional changes in host cells reveals that cAIMP treatment rescues cells from the harmful effects of CHIKV-induced dysregulation of cell repair, immune, and metabolic pathways.
Conclusion
Given their already-demonstrated epidemic potential. The UCLA study has identified potential broad-spectrum antiviral agents that could target multiple families of RNA viruses, including those posing a significant threat to future pandemics. The cyclic dinucleotide (CDN) STING agonists demonstrated the most significant antiviral potential, targeting the Chikungunya virus and multiple respiratory viruses, including the SARS-CoV-2 virus, showing therapeutic promise for cancer immunotherapy. Given their already-demonstrated epidemic potential, finding effective broad-spectrum treatments against these viruses is crucial. The researchers aim to develop these antivirals in combination with existing ones and make them readily available in the event of future respiratory and arboviral disease outbreaks.
