BPR3P0128, a non-nucleoside RNA-dependent RNA polymerase inhibitor, inhibits SARS-CoV-2 variants of concern and exerts synergistic antiviral activity in combination with remdesivir.

Viral RNA-dependent RNA polymerase (RdRp), a highly conserved molecule in RNA viruses, has recently emerged as a promising drug target for broad-acting inhibitors. Through a Vero E6-based anti-cytopathic effect assay, we found that BPR3P0128, which incorporates a quinoline core similar to hydroxychloroquine, outperformed the adenosine analog remdesivir in inhibiting RdRp activity (EC = 0.66 µM and 3 µM, respectively).

Selection of viral capsids and promoters affects the efficacy of rescue of -deficient cochlea.

Adeno-associated virus (AAV)-mediated gene transfer has shown promise in rescuing mouse models of genetic hearing loss, but how viral capsid and promoter selection affects efficacy is poorly characterized. Here, we tested combinations of AAVs and promoters to deliver , mutations in which are associated with hearing loss in humans. mice display severe cochlear hair cell degeneration, loss of auditory brainstem responses, and delayed loss of spiral ganglion neurons.

TMPRSS3 expression is limited in spiral ganglion neurons: implication for successful cochlear implantation.

Background: It is well established that biallelic mutations in transmembrane protease, serine 3 () cause hearing loss. Currently, there is controversy regarding the audiological outcomes after cochlear implantation (CI) for -associated hearing loss. This controversy creates confusion among healthcare providers regarding the best treatment options for individuals with -related hearing loss.

Regulation of the proteostasis network during enterovirus infection: A feedforward mechanism for EV-A71 and EV-D68.

The proteostasis network guarantees successful protein synthesis, folding, transportation, and degradation. Mounting evidence has revealed that this network maintains proteome integrity and is linked to cellular physiology, pathology, and virus infection. Human enterovirus A71 (EV-A71) and EV-D68 are suspected causative agents of acute flaccid myelitis, a severe poliomyelitis-like neurologic syndrome with no known cure.

Rosmarinic acid exhibits broad anti-enterovirus A71 activity by inhibiting the interaction between the five-fold axis of capsid VP1 and cognate sulfated receptors.

Enterovirus A71 (EV-A71), a positive-stranded RNA virus of the Picornaviridae family, may cause neurological complications or fatality in children. We examined specific factors responsible for this virulence using a chemical genetics approach. Known compounds from an anti-EV-A71 herbal medicine, (Danshen), were screened for anti-EV-A71.

The double-edged sword of endoplasmic reticulum stress in uremic sarcopenia through myogenesis perturbation.

Background: Sarcopenia is the age-related degeneration characterized with the decline of skeletal muscle mass, strength, and function. The imbalance of protein synthesis and degradation which jeopardizes immune, hormone regulation, and muscle-motor neuron connection is the main cause of sarcopenia. There is limited knowledge regarding molecular mechanism of sarcopenia.

Ochratoxin A induces ER stress and apoptosis in mesangial cells via a NADPH oxidase-derived reactive oxygen species-mediated calpain activation pathway.

Ochratoxin A (OTA) contaminated food increases reactive oxygen species (ROS) production in glomerulus and causes glomerulopathy. The molecular mechanisms still remain uncertain. In this study, we used mouse and rat glomerular mesangial cells and delineate the signaling pathway behind the OTA-triggered cell apoptosis.

Chemical constituents of Plectranthus amboinicus and the synthetic analogs possessing anti-inflammatory activity.

This study demonstrates that compounds 1-4 from an extract of Plectranthus amboinicus inhibit the binding of AP-1 to its consensus DNA sequence. Thymoquinone (5) was further identified as a nonpolar ingredient from the hexane extract of P. amboinicus to suppress the expression of lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-α).