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The porcine reproductive and respiratory syndrome virus (PRRSV) belongs to the Arteriviridae family and is a single-stranded, positively stranded RNA virus. The currently available PRRSV vaccines are mainly inactivated and attenuated vaccines, yet none of the commercial vaccines can provide comprehensive, long-lasting, and effective protection against PRRSV. SR717 is a pyridazine-3-carboxamide compound, which is commonly used as a non-nucleoside STING agonist with antitumor and antiviral activities. Nevertheless, there is no evidence that SR717 has any antiviral effects against PRRSV. In this study, a dose-dependent inhibitory effect of SR717 was observed against numerous strains of PRRSV using qRT-PCR, IFA, and WB methods. Furthermore, SR717 was found to stimulate the production of anti-viral molecules and trigger the activation of the signaling cascade known as the stimulator of interferon genes (STING) pathway, which contributed to hindering the reproduction of viruses by a certain margin. Collectively, these results indicate that SR717 is capable of inhibiting PRRSV infection in vitro and may have potential as an antiviral drug against PRRSV.
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http://dx.doi.org/10.3390/v16091373 | DOI Listing |
Biomaterials
September 2025
Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China. Electronic address:
The stimulator of interferon genes (STING) pathway represents a promising target in cancer immunotherapy. However, the clinical translation of cyclic dinucleotide (CDN)-based STING agonists remains hindered by insufficient formation of functional CDN-STING complexes. This critical bottleneck arises from two interdependent barriers: inefficient cytosolic CDN delivery and tumor-specific STING silencing via DNA methyltransferase-mediated promoter hypermethylation.
View Article and Find Full Text PDFJ Integr Neurosci
August 2025
Institute of Neuroscience and Third Affiliated Hospital, Zhengzhou University, 450052 Zhengzhou, Henan, China.
Background: Germinal matrix hemorrhage (GMH) is a common complication of premature infants with lifelong neurological consequences. Inflammation-mediated blood-brain barrier (BBB) disruption has been implicated as a main mechanism of secondary brain injury after GMH. The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a crucial role in inflammation, yet its involvement in GMH pathophysiology remains unclear.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
September 2025
Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, P.R. China.
The stimulator of interferon genes (STING) pathway is a central target in cancer immunotherapy, but current STING agonist therapies lack precision control, leading to suboptimal therapeutic outcomes and systematic adverse effects. Herein, we engineered a dual-locked immuno-polymeric nanoplatform (IPN) with precise spatiotemporal control over the release of STING agonists to enhance cancer immunotherapy. This platform, constructed from biocompatible poly(β-amino esters) (PBAE), incorporates the STING agonist (MSA-2) covalently linked via ester bonds, which is co-assembled with a sonosensitizer.
View Article and Find Full Text PDFCell Rep Med
August 2025
Department of Biochemistry, Stanford University, Stanford, CA 94305, USA; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA; Arc Institute, Palo Alto, CA 94304, USA. Electronic address:
Only one in five patients respond to immune checkpoint inhibitors, which primarily target adaptive immunity. Ectonucleotide pyrophosphatase/phophodiesterase 1 (ENPP1), the dominant hydrolase of 2'3'-cyclic-GMP-AMP (cGAMP) that suppresses downstream stimulator of interferon genes (STING) signaling, has emerged as a promising innate immunotherapy target. However, existing ENPP1 inhibitors have been optimized for prolonged systemic residence time rather than effective target inhibition within tumors.
View Article and Find Full Text PDFNeurocrit Care
September 2025
Department of Rehabilitation, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Background: Traumatic brain injury (TBI) is a major life-threatening event. In addition to neurological deficits, it can lead to long-term impairments of cognitive function. The vagus nerve (VN) provides a direct communication conduit between the central nervous system and the periphery, and modulation of the inflammatory reflex via electrical stimulation of the vagus nerve (VNS) shows efficacy in ameliorating pathology in neurodegenerative diseases.
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