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A wound evolves with variable pHs depending on the healing stage, and the maintenance of mild acidic condition can help healing by deterring the formation of a biofilm. Herein, a dual‐layer wound dressing with an acid‐responsive zeolitic imidazolate framework–8 (ZIF‐8) layer and an acid‐modulating layer is designed to control the acid‐dependent release of therapeutic agents for the improved healing process. The outer dressing layer is coated with curcumin‐incorporated ZIF‐8, where curcumin and zinc ions are released upon dissociation of ZIF‐8 in an acidic condition. The inner layer, a pH modulator, is fabricated by electrospinning polyvinylpyrrolidone with addition of acetic acid. In vitro release test shows that the outer layer dressing attains a considerably higher release of curcumin and Zn2+ under an acidic condition. Combined with the inner acidic layer, the dual layer dressing exhibits facilitated release of effective agents regardless of environmental pHs, attributed to the proper pH modulation to about 6.5. The anti‐oxidant activity of curcumin and antibacterial activity of Zn2+ are confirmed. The study highlights the novel proof‐of‐concept design of active wound dressing demonstrating the dual functions of pH regulation and the stimulus‐responsive drug delivery. [ABSTRACT FROM AUTHOR]

The Japanese encephalitis virus (JEV) is prevalent in Asian countries, including Korea, Japan, China, Vietnam, and India. JEV is transmitted to humans by Culex mosquitoes. Despite extensive research efforts, no approved antiviral agents are currently available, although JE can be prevented by vaccination. DNA endonuclease-targeted CRISPR trans reporter (DETECTR) is a newly emerging CRISPR-Cas12a-based molecular diagnostic method combined with isothermal nucleic acid amplification. In this study, DETECTR with reverse transcription–recombinase polymerase amplification (RT-RPA) was effectively utilized for JEV diagnosis and detected down to 10 RNA copies for JEV genotype I (GI) and 1 × 102 copies for both GIII and GV, achieving similar sensitivity to RT-PCR while displaying no cross-reaction with other viruses. A one-tube, one-temperature format of DETECTR was further developed, and its efficiency compared with that of conventional DETECTR. [ABSTRACT FROM AUTHOR]

Screening of the antiviral and virucidal activities of ethanol extracts from plants endemic to the Republic of Korea revealed the inhibitory activity of a 70% ethanol extract of the whole plant of A. pseudoglehnii (APE) against influenza virus infection. Two chlorophyll derivatives, ethyl pheophorbides a and b, isolated as active components of APE, exerted virucidal effects with no evident cytotoxicity. These compounds were effective only under conditions of direct incubation with the virus, and exerted no effects on the influenza A virus (IAV) surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). Interestingly, virucidal activities of ethyl pheophorbides a and b were observed against enveloped but not non-enveloped viruses, suggesting that these compounds act by affecting the integrity of the viral membrane and reducing infectivity. [ABSTRACT FROM AUTHOR]

Kaempferol, a natural flavonoid abundantly found in plants, is known to have pharmacological properties, such as anti-inflammatory and anti-cancer effects. In this study, we investigated the antiviral effects of kaempferol against a varicella-zoster virus (VZV) clinical isolate in vitro. We found that kaempferol significantly inhibited VZV replication without exhibiting cytotoxicity. Kaempferol exerted its antiviral effect at a similar stage of the VZV life cycle as acyclovir, which inhibits VZV DNA replication. Taken together, our results suggest that kaempferol inhibits VZV infection by blocking the DNA replication stage in the viral life cycle. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome virus (SFTSV) infection is commonly reported in countries of Northeast Asia including China, Japan and South Korea. The majority of the SFTS patients are elderly and the average fatality rate is more than 10%. A rapid and sensitive diagnostic method to monitor and prevent SFTSV transmission remains an urgent clinical challenge. In this study, we developed a molecular diagnostic technique for detection of SFTSV using the CRISPR-Cas12a system combined with reverse transcription recombinase polymerase amplification (RT-RPA). Using this method, we successfully diagnosed SFTSV infections with the reaction time of 50 min from blood plasma without cross-reactivity to other viruses, supporting its application for rapid and sensitive diagnosis of SFTS. Author summary: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by Dabie bandavirus, also known as SFTSV, and reported in countries of Northeast Asia including China, Japan and South Korea. The average fatality rate is more than 10% and reported to increase with age. Currently, no vaccines or targeted treatments for SFTS are available and only symptomatic therapy is offered. Thus, SFTSV diagnosis at early stages is critical for successful therapeutic outcomes. In this study, we developed a molecular diagnostic technique for detection of SFTSV using the CRISPR-Cas12a system combined with reverse transcription recombinase polymerase amplification (RT-RPA). Using this method, we successfully diagnosed SFTSV infections under isothermal conditions with the reaction time of 50 min from blood plasma. [ABSTRACT FROM AUTHOR]

Two new pyrrolosesquiterpenes, glaciapyrroles D (1) and E (2) were discovered along with the previously reported glaciapyrrole A (3) from Streptomyces sp. GGS53 strain isolated from deep-sea sediment. This study elucidated the planar structures of 1 and 2 using nuclear magnetic resonance (NMR), mass spectrometry (MS), ultraviolet (UV), and infrared (IR) spectroscopic data. The absolute configurations of the glaciapyrroles were determined by Mosher's method, circular dichroism spectroscopy, and X-ray crystallography. Under 366 nm UV irradiation, the glaciapyrroles were systematically converted to the corresponding photoglaciapyrroles (4–6) via photoisomerization, resulting in the diversification of the glaciapyrrole family compounds. The transformation of the glaciapyrrole Z to E isomers occurred in a 1:1 ratio, based on virtual validation of the photoisomerization of these olefinic compounds by 1H-NMR spectroscopy and liquid chromatography/mass spectrometry (LC/MS) analysis. Finally, when encapsulated in poly(lactic-co-glycolic acid) nanoparticles, glaciapyrrole E and photoglaciapyrrole E displayed significant inhibitory activity against influenza A virus. This is the first report of antiviral effects from glaciapyrrole family compounds, whose biological functions have only been subjected to limited studies so far. [ABSTRACT FROM AUTHOR]

Dysregulated activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway by self-DNA contributes to interferonopathy and promotes autoimmune diseases. To identify potential suppressors of STING-induced type I interferon (IFN) induction, ethanol extracts of medicinal plants were screened for inhibitory activity against IFN-ß promoter activation. Notably, 70% ethanol extract of Cephalotaxus koreana specifically down-regulated STING-induced, but not TBK1- or IRF3-induced, IFN-ß promoter activity. The compounds exerting inhibitory activity specifically against STING-mediated IFN-ß promoter activation were identified as ester alkaloids isolated from the genus, Cephalotaxus, homoharringtonine and harringtonine. Furthermore, these two compounds inhibited 2’3’-cGAMP-induced IFN-stimulated gene expression and interaction between STING and TBK1. These suppressive effects were not observed with cephalotaxine devoid of the ester side-chain. Our data support the potential utility of homoharringtonine and harringtonine to treat STING-associated interferonopathy and autoimmune diseases. [ABSTRACT FROM AUTHOR]

A rapid and accurate on-site diagnostic test for pathogens including influenza viruses is critical for preventing the spread of infectious diseases. Two types of influenza virus, A and B cause seasonal flu epidemics, whereas type A can cause influenza pandemics. To specifically detect influenza A (IAV) and B (IBV) viruses, we developed a clustered, regularly interspaced, short palindromic repeats (CRISPR) and CRISPR-associated (Cas) system-based assay. By coupling reverse transcription recombinase polymerase amplification (RT-RPA) and reverse transcription loop-mediated isothermal amplification (RT-LAMP), a CRISPR-Cas12a DNA endonuclease-targeted CRISPR trans-reporter (DETECTR) detected IAV and IBV titers as low as 1 × 100 plaque forming units (PFUs) per reaction without exhibiting cross-reactivity. Only 75 to 85 min were required to detect IAV and IBV, depending on isothermal nucleic acid amplification methods, and results were verified using a lateral flow strip assay that does not require additional analytic equipment. Taken together, our findings establish RT-RPA and RT-LAMP-coupled DETECTR-based diagnostic tests for rapid, specific and high-sensitivity detection of IAV and IBV using fluorescence and lateral flow assays. The diagnostic test developed in this study can be used to distinguish IAV and IBV infections, a capability that is necessary for monitoring and preventing the spread of influenza epidemics and pandemics. [ABSTRACT FROM AUTHOR]

Viral infection-induced activation of inflammasome complexes has both positive and negative effects on the host. Proper activation of inflammasome complexes induces down-stream effector mechanisms that inhibit viral replication and promote viral clearance, whereas dysregulated activation has detrimental effects on the host. Coronaviruses, including SARS-CoV and MERS-CoV, encode viroporins that activate the NLRP3 inflammasome, and the severity of coronavirus disease is associated with the inflammasome activation. Although the NLRP3 inflammasome activation is implicated in the pathogenesis of coronaviruses, these viruses must evade inflammasome-mediated antiviral immune responses to establish primary replication. Screening of a complementary DNA (cDNA) library encoding 28 SARS-CoV-2 open reading frames (ORFs) showed that two nonstructural proteins (NSPs), NSP1 and NSP13, inhibited caspase-1-mediated IL-1β activation. NSP1 amino acid residues involved in host translation shutoff and NSP13 domains responsible for helicase activity were associated with caspase-1 inhibition. In THP-1 cells, both NSP1 and NSP13 significantly reduced NLRP3-inflammasome-induced caspase-1 activity and IL-1β secretion. These findings indicate that SARS-CoV-2 NSP1 and NSP13 are potent antagonists of the NLRP3 inflammasome. [ABSTRACT FROM AUTHOR]

We previously reported that the ethyl acetate (EtOAc) fraction of a 70% ethanol extract of Elaeocarpus sylvestris (ESE) inhibits varicella-zoster virus (VZV) and human cytomegalovirus (HCMV) replication in vitro. PGG (1,2,3,4,6-penta-O-galloyl-ß-D-glucose) is a major chemical constituent of the EtOAc fraction of ESE that inhibits VZV but not HCMV replication. In this study, we comprehensively screened the chemical compounds identified in the EtOAc fraction of ESE for potential antiviral properties. Among the examined compounds, quercetin and isoquercitrin displayed potent antiviral activities against both VZV and HCMV with no significant cytotoxic effects. Both compounds strongly suppressed the expression of VZV and HCMV immediate–early (IE) genes. Our collective results indicated that, in addition to PGG, quercetin and isoquercitrin are bioactive compounds in the EtOAc fraction of ESE that effectively inhibit human herpesvirus replication. [ABSTRACT FROM AUTHOR]