Synthesis and evaluation of N-arylindazole-3-carboxamide derivatives as novel antiviral agents against SARS-CoV-2.

N-Arylindazole-3-carboxamide derivatives synthesized from an anti-MERS-CoV hit compound showed potent inhibitory activities against SARS-CoV-2. Among them, 5-chloro-N-(3,5-dichlorophenyl)-1H-indazole-3-carboxamide (4a) exhibited a potent inhibitory effect (EC = 0.69 µM), low cytotoxicity, and satisfactory in vitro PK profiles.

Discovery of new acetamide derivatives of 5-indole-1,3,4-oxadiazol-2-thiol as inhibitors of HIV-1 Tat-mediated viral transcription.

Human immunodeficiency virus-1 (HIV-1) encodes a transcriptional factor called Tat, which is critical for viral transcription. Tat-mediated transcription is highly ordered apart from the cellular manner; therefore, it is considered a target for developing anti-HIV-1 drugs. However, drugs targeting Tat-mediated viral transcription are not yet available.

Drosophila melanogaster as potential alternative animal model for evaluating acute inhalation toxicity.

Drosophila melanogaster (D. melanogaster) is a promising model biological system. It has a short life cycle and can provide a substantial number of specimens suitable for comprehensive genetic and molecular analyses in a short time.

subcritical-water extracts as ameliorant of insulin resistance induced by high-glucose in zebrafish and dexamethasone in L6 myotubes.

Background And Aim: Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to insulin. Loss of insulin sensitivity disrupts glucose homeostasis and elevates the risk of developing the metabolic syndrome that includes Type 2 diabetes. This study assesses the effect on subcritical-water extract of (GC) at 210 °C (GCSW210) in IR induction models of high glucose (HG)-induced zebrafish larvae and dexamethasone (DEX)-induced L6 myotubes.

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.

A Novel Time-Resolved Fluorescence Resonance Energy Transfer Assay for the Discovery of Small-Molecule Inhibitors of HIV-1 Tat-Regulated Transcription.

Human immunodeficiency virus-1 (HIV-1) transactivator (Tat)-mediated transcription is essential for HIV-1 replication. It is determined by the interaction between Tat and transactivation response (TAR) RNA, a highly conserved process representing a prominent therapeutic target against HIV-1 replication. However, owing to the limitations of current high-throughput screening (HTS) assays, no drug that disrupts the Tat-TAR RNA interaction has been uncovered yet.

Exploitation of a novel adjuvant for polymyxin B against multidrug-resistant Acinetobacter baumannii.

Background: Although polymyxin has been used as a last-resort antibiotic against resistant bacteria, its use is restricted due to nephrotoxicity and neurotoxicity. While the present antibiotic resistance issue compels clinicians to reconsider polymyxin use in severe illness cases, polymyxin-resistant microorganisms exert an effect.

Objectives: To address the issue of antibiotic resistance, the cycle of developing new antibiotics to counteract emerging resistance must be discontinued.

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.

Convolutional neural network-based classification of cervical intraepithelial neoplasias using colposcopic image segmentation for acetowhite epithelium.

Colposcopy is a test performed to detect precancerous lesions of cervical cancer. Since cervical cancer progresses slowly, finding and treating precancerous lesions helps prevent cervical cancer. In particular, it is clinically important to detect high-grade squamous intraepithelial lesions (HSIL) that require surgical treatment among precancerous lesions of cervix.

Identification of 3-Oxindole Derivatives as Small Molecule HIV-1 Inhibitors Targeting Tat-Mediated Viral Transcription.

The heterocyclic indole structure has been shown to be one of the most promising scaffolds, offering various medicinal advantages from its wide range of biological activity. Nonetheless, the significance of 3-oxindole has been less known. In this study, a series of novel 3-oxindole-2-carboxylates were synthesized and their antiviral activity against human immunodeficiency virus-1 (HIV-1) infection was evaluated.

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.

Differential epithelial and stromal LGR5 expression in ovarian carcinogenesis.

Lgr5 has been identified as a marker of the stem/progenitor cells in the murine ovary and oviduct by lineage tracing. However, little is known regarding LGR5 expression or its functional significance in human ovary tissues. Here, using RNA in situ hybridization and/or immunohistochemistry, we thoroughly investigated LGR5 expression in normal human ovaries, fallopian tubes and various ovarian tumors.

Extreme elevation of CA 19-9 levels in mature cystic teratoma without any complications: A case report.

Introduction And Importance: Carbohydrate antigen 19-9 (CA 19-9) can be increased in benign ovarian cysts, but extreme elevation is rare.

Case Presentation: We present a case of a mature cystic teratoma with extremely elevated CA 19-9 levels. After ovarian cystectomy, the level of CA 19-9 was decreased.

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.

EPHB2 expression is associated with intestinal phenotype of gastric cancer and indicates better prognosis by suppressing gastric cancer migration.

The protein tyrosine kinase Ephrin type-B receptor 2 (EPHB2) belongs to one of the intestinal stem cell signature genes and plays a crucial role in maintaining the crypt-villous axis. Herein, we aimed to investigate the expression of EPHB2 during gastric carcinogenesis and evaluated its prognostic and functional significance in gastric cancer (GC). EPHB2 expression was upregulated in intestinal metaplasia and GCs compared to normal antral and fundic glands.

Anticoronaviral Activity of the Natural Phloroglucinols, Dryocrassin ABBA and Filixic Acid ABA from the Rhizome of by Targeting the Main Protease of SARS-CoV-2.

The rhizome of Nakai. (Dryopteridaceae) has been used in traditional medicine in East Asia and has recently been reported to have anticancer, anti-inflammation, and antibacterial activity as well as antiviral activity. Natural phloroglucinols from , dryocrassin ABBA and filixic acid ABA were reported to inhibit influenza virus infection with an inhibitory activity on neuraminidase.

Huge follicular carcinoma originated from struma ovarii in young woman; Extremely rare case.

Introduction: Struma ovarii (SO) is a rare ovarian mature teratoma which is composed of 50% or more thyroid tissues. Malignant transformation is reported to occur in less than 5% of all cases, and it leads to 5-6% metastatic disease. The most common type is a papillary carcinoma.

Broad Spectrum Antiviral Properties of Cardiotonic Steroids Used as Potential Therapeutics for Emerging Coronavirus Infections.

Cardiotonic steroids are steroid-like natural compounds known to inhibit Na/K-ATPase pumps. To develop a broad-spectrum antiviral drug against the emerging coronavirus infection, this study assessed the antiviral properties of these compounds. The activity of seven types of cardiotonic steroids against the MERS-CoV, SARS-CoV, and SARS-CoV-2 coronavirus varieties was analyzed using immunofluorescence antiviral assay in virus-infected cells.

Exposure to cigarette smoke exacerbates polyhexamethylene guanidine-induced lung fibrosis in mice.

Cigarette smoke (CS) is the leading cause of chronic pulmonary diseases, including lung cancer, chronic obstructive pulmonary disease, and pulmonary fibrosis. In this study, we aimed to investigate the effects of repeated CS exposure on polyhexamethylene guanidine (PHMG)-induced pulmonary fibrosis in mice. A single intratracheal instillation of 0.

Allosteric Inhibition of the Tumor-Promoting Interaction Between Exon 2-Depleted Splice Variant of Aminoacyl-Transfer RNA Synthetase-Interacting Multifunctional Protein 2 and Heat Shock Protein 70.

Although protein-protein interactions (PPIs) have emerged as an attractive therapeutic target space, the identification of chemicals that effectively inhibit PPIs remains challenging. Here, we identified through library screening a chemical probe (compound ) that can inhibit the tumor-promoting interaction between the oncogenic factor exon 2-depleted splice variant of aminoacyl-transfer RNA synthetase-interacting multifunctional protein 2 (AIMP2-DX2) and heat shock protein 70 (HSP70). We found that compound binds to the N-terminal subdomain of glutathione -transferase (GST-N) of AIMP2-DX2, causing a direct steric clash with HSP70 and an intramolecular interaction between the N-terminal flexible region and the GST-N of AIMP2-DX2, which induces masking of the HSP70 binding region during molecular dynamics and mutation studies.

An Overview of Human Immunodeficiency Virus-1 Antiretroviral Drugs: General Principles and Current Status.

Treatment with highly active antiretroviral therapy (HAART) can prolong a patient's life-span by disrupting pivotal steps in the replication cycle of the human immunodeficiency virus-1 (HIV-1). However, drug resistance is emerging as a major problem worldwide due to the prolonged period of treatment undergone by HIV-1 patients. Since the approval of zidovudine in 1987, over thirty antiretroviral drugs have been categorized into the following six distinct classes based on their biological function and resistance profiles: (1) nucleoside analog reverse-transcriptase inhibitors; (2) non-nucleoside reverse transcriptase inhibitors; (3) integrase strand transferase inhibitors; (4) protease inhibitors; (5) fusion inhibitors; and (6) co-receptor antagonists.

Cancer Patients' Willingness to Take COVID-19 Vaccination: A Nationwide Multicenter Survey in Korea.

Considering the high morbidity and mortality of Coronavirus disease 2019 (COVID-19) in patients with malignancy, they are regarded as a priority for COVID-19 vaccination. However, general vaccine uptake rates among cancer patients are known to be lower than in their healthy counterparts. Thus, we aimed to investigate the attitude and acceptance rates for the COVID-19 vaccine in cancer patients and identify predictive factors for vaccination that could be modified to increase vaccine uptake rates, via a paper-based survey (58 items over six domains).

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.

Lycorine, a non-nucleoside RNA dependent RNA polymerase inhibitor, as potential treatment for emerging coronavirus infections.

Background: Highly effective novel treatments need to be developed to suppress emerging coronavirus (CoV) infections such as COVID-19. The RNA dependent RNA polymerase (RdRp) among the viral proteins is known as an effective antiviral target. Lycorine is a phenanthridine Amaryllidaceae alkaloid isolated from the bulbs of Lycoris radiata (L'Hér.