Immune-Stimulating Potential of LM1019 in RAW 264.7 Cells and Immunosuppressed Mice Induced by Cyclophosphamide.

Probiotics, including (), have gained recognition for their potential health benefits, such as enhancing immune function, maintaining gut health, and improving nutrient absorption. This study investigated the effectiveness of LM1019 (LM1019) in enhancing immune function. In RAW 264.

Novel SARS-CoV-2 entry inhibitors, 2-anilinoquinazolin-4(3H)-one derivatives, show potency as SARS-CoV-2 antivirals in a human ACE2 transgenic mouse model.

The ongoing COVID-19 has not only caused millions of deaths worldwide, but it has also led to economic recession and the collapse of public health systems. The vaccines and antivirals developed in response to the pandemic have improved the situation markedly; however, the pandemic is still not under control with recurring surges. Thus, it is still necessary to develop therapeutic agents.

Discovery of 2-aminoquinolone acid derivatives as potent inhibitors of SARS-CoV-2.

The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to threaten human health and create socioeconomic problems worldwide. A library of 200,000 small molecules from the Korea Chemical Bank (KCB) were evaluated for their inhibitory activities against SARS-CoV-2 in a phenotypic-based screening assay to discover new therapeutics to combat COVID-19. A primary hit of this screen was the quinolone structure-containing compound 1.

Optimization of 2-Aminoquinazolin-4-(3)-one Derivatives as Potent Inhibitors of SARS-CoV-2: Improved Synthesis and Pharmacokinetic Properties.

We previously reported the potent antiviral effect of the 2-aminoquinazolin-4-(3)-one , which shows significant activity (IC = 0.23 μM) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with no cytotoxicity. However, it is necessary to improve the in vivo pharmacokinetics of compound because its area under the curve (AUC) and maximum plasma concentration are low.

Trial of Revealed the Complex Network Correlations Between Gut Microbiota and Health Promotional Effects.

Complete genome sequence analysis of subsp. BCBL-583 isolated from a Korean female fecal sample showed no virulence factor or antibiotic resistance gene, suggesting human safety. In addition, this strain has oxygen and heat tolerance genes for food processing, and cholesterol reduction and mucin adhesion-related genes were also found.

Synthesis and biological evaluation of 2-benzylaminoquinazolin-4(3)-one derivatives as a potential treatment for SARS-CoV-2.

Despite the continuing global crisis caused by coronavirus disease 2019 (COVID-19), there is still no effective treatment. Therefore, we designed and synthesized a novel series of 2-benzylaminoquinazolin-4(3)-one derivatives and demonstrated that they are effective against SARS-CoV-2. Among the synthesized derivatives, 7-chloro-2-(((4-chlorophenyl)(phenyl)methyl)amino)quinazolin-4(3)-one (Compound ) showed highest anti-SARS-CoV-2 activity, with a half-maximal inhibitory concentration value greater than that of remdesivir (IC = 4.

Design, synthesis and biological evaluation of 2-aminoquinazolin-4(3H)-one derivatives as potential SARS-CoV-2 and MERS-CoV treatments.

Despite the rising threat of fatal coronaviruses, there are no general proven effective antivirals to treat them. 2-Aminoquinazolin-4(3H)-one derivatives were newly designed, synthesized, and investigated to show the inhibitory effects on SARS-CoV-2 and MERS-CoV. Among the synthesized derivatives, 7-chloro-2-((3,5-dichlorophenyl)amino)quinazolin-4(3H)-one (9g) and 2-((3,5-dichlorophenyl)amino)-5-hydroxyquinazolin-4 (3H)-one (11e) showed the most potent anti-SARS-CoV-2 activities (IC < 0.

Discovery of cyclic sulfonamide derivatives as potent inhibitors of SARS-CoV-2.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) continues to spread worldwide, with 25 million confirmed cases and 800 thousand deaths. Effective treatments to target SARS-CoV-2 are urgently needed. In the present study, we have identified a class of cyclic sulfonamide derivatives as novel SARS-CoV-2 inhibitors.

Identification of 4-anilino-6-aminoquinazoline derivatives as potential MERS-CoV inhibitors.

New therapies for treating coronaviruses are urgently needed. A series of 4-anilino-6-aminoquinazoline derivatives were synthesized and evaluated to show high anti-MERS-CoV activities. N-(3-Chloro-4-fluorophenyl)-N-(3-methoxybenzyl)quinazoline-4,6-diamine (1) has been identified in a random screen as a hit compound for inhibiting MERS-CoV infection.

Study on the 2-Phenylchroman-4-One Derivatives and their -MERS-CoV Activities.

Study on the 2-phenylchroman-4-one derivatives and their anti-MERS-CoVactivities.

6'-β-Fluoro-Homoaristeromycin and 6'-Fluoro-Homoneplanocin A Are Potent Inhibitors of Chikungunya Virus Replication through Their Direct Effect on Viral Nonstructural Protein 1.

Alphaviruses are arthropod-borne, positive-stranded RNA viruses capable of causing severe disease with high morbidity. Chikungunya virus (CHIKV) is an alphavirus that causes a febrile illness which can progress into chronic arthralgia. The current lack of vaccines and specific treatment for CHIKV infection underscores the need to develop new therapeutic interventions.

Identification of 6'-β-fluoro-homoaristeromycin as a potent inhibitor of chikungunya virus replication.

We have reported on aristeromycin (1) and 6'-fluorinated-aristeromycin analogues (2), which are active against RNA viruses such as Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), Zika virus (ZIKV), and Chikungunya virus (CHIKV). However, these exhibit substantial cytotoxicity. As this cytotoxicity may be attributed to 5'-phosphorylation, we designed and synthesized one-carbon homologated 6'-fluorinated-aristeromycin analogues.

Natural Bis-Benzylisoquinoline Alkaloids-Tetrandrine, Fangchinoline, and Cepharanthine, Inhibit Human Coronavirus OC43 Infection of MRC-5 Human Lung Cells.

and other related species of are the major sources of the bis-benzylisoquinoline alkaloids tetrandrine (TET), fangchinoline (FAN), and cepharanthine (CEP). Although the pharmacological properties of these compounds include anticancer and anti-inflammatory activities, the antiviral effects of these compounds against human coronavirus (HCoV) remain unclear. Hence, the aims of the current study were to assess the antiviral activities of TET, FAN, and CEP and to elucidate the underlying mechanisms in HCoV-OC43-infected MRC-5 human lung cells.

Synthesis and biological evaluation of 3-acyl-2-phenylamino-1,4-dihydroquinolin-4(1H)-one derivatives as potential MERS-CoV inhibitors.

3-Acyl-2-phenylamino-1,4-dihydroquinolin-4(1H)-one derivatives were synthesized and evaluated to show high anti-MERS-CoV inhibitory activities. Among them, 6,8-difluoro-3-isobutyryl-2-((2,3,4-trifluorophenyl)amino)quinolin-4(1H)-one (6u) exhibits high inhibitory effect (IC = 86 nM) and low toxicity (CC > 25 μM). Moreover, it shows good metabolic stability, low hERG binding affinity, no cytotoxicity, and good in vivo PK properties.

Design, Synthesis, and Anti-RNA Virus Activity of 6'-Fluorinated-Aristeromycin Analogues.

The 6'-fluorinated aristeromycins were designed as dual-target antiviral compounds aimed at inhibiting both the viral RNA-dependent RNA polymerase (RdRp) and the host cell -adenosyl-l-homocysteine (SAH) hydrolase, which would indirectly target capping of viral RNA. The introduction of a fluorine at the 6'-position enhanced the inhibition of SAH hydrolase and the activity against RNA viruses. The adenosine and -methyladenosine analogues showed potent inhibition against SAH hydrolase, while only the adenosine derivatives exhibited potent antiviral activity against all tested RNA viruses such as Middle East respiratory syndrome-coronavirus (MERS-CoV), severe acute respiratory syndrome-coronavirus, chikungunya virus, and/or Zika virus.

Isolation and Characterization of subsp. BCBL-583 for Probiotic Applications in Fermented Foods.

Recent human gut microbiome studies have supported that the genus is one of the most beneficial bacteria for human intestinal health. To develop a new probiotic strain for functional food applications, fourteen fecal samples were collected from healthy Koreans and the strain BCBL-583 was newly selected and isolated from a 25-year-old Korean woman's fecal sample using the selective medium for . Subsequent fructose-6-phosphate phosphoketolase (F6PPK) test and 16S rRNA gene sequencing analysis of the strain BCBL-583 confirmed that it belongs to subsp.

Asymmetric Synthesis of (-)-6'-β-Fluoro-aristeromycin via Stereoselective Electrophilic Fluorination.

(-)-6'-β-Fluoro-aristeromycin (2), a potent inhibitor of S-adenosylhomocysteine (AdoHcy) hydrolase, has been synthesized via stereoselective electrophilic fluorination followed by a purine base build-up approach. Interestingly, purine base condensation using a cyclic sulfate resulted in a synthesis of (+)-5'-β-fluoro-isoaristeromycin (2a). Computational analysis indicates that the fluorine atom controlled the regioselectivity of the purine base substitution.

Cardiomyopathy after local infiltration or application of epinephrine for plastic surgery under general anesthesia : Two cases report.

Catecholamine-induced cardiomyopathy rarely occurs after local epinephrine infiltration. We experienced two patients with catecholamine induced cardiomyopathies. An 8-yr-old girl was scheduled for closed reduction of a nasal bone fracture.