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.

A Stool DNA-Based SDC2 Methylation Test for the Early Detection of Colorectal Cancer in an Asymptomatic, High-Risk Population: A Multicenter Prospective Randomized Trial.

Introduction: Noninvasive stool DNA-based methylation testing has emerged as an effective strategy for the early colorectal cancer (CRC) detection. Syndecan-2 (SDC2) methylation frequently occurs in all stages of CRC; therefore, the aim of this study was to evaluate the clinical performance of a stool DNA-based SDC2 methylation test for detecting CRC in asymptomatic or high-risk CRC populations.

Methods: This multicenter prospective study was conducted to determine the clinical performance of the SDC2 methylation test on stool DNA using real-time polymerase chain reaction.

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.

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.

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.

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.

Colorectal cancer screening using a stool DNA-based SDC2 methylation test: a multicenter, prospective trial.

Background: Prevention and early detection of colorectal cancer (CRC) is a global priority, with many countries conducting population-based CRC screening programs. Although colonoscopy is the most accurate diagnostic method for early CRC detection, adherence remains low because of its invasiveness and the need for extensive bowel preparation. Non-invasive fecal occult blood tests or fecal immunochemical tests are available; however, their sensitivity is relatively low.

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.

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.

Percutaneous Closure of Gastrostomy Using a Suture-Mediated Vascular Closure Device in a Swine Model.

Purpose: After any procedure through the percutaneous gastrostomy (PG), a PG tube should be kept in place until a mature tract develops. For this period of maturation which takes about 2 to 4 weeks, tube dislodgement, leakage, or peritonitis can occur. Complications from PG tube maintenance can be prevented by closing the PG immediately after the procedure.

KRCA-0008 suppresses ALK-positive anaplastic large-cell lymphoma growth.

Anaplastic lymphoma kinase (ALK), which belongs to the insulin receptor tyrosine kinase superfamily, plays an important role in nervous system development. Due to chromosomal translocations, point mutations, and gene amplification, constitutively activated ALK has been implicated in a variety of human cancers, including anaplastic large-cell lymphoma (ALCL), non-small cell lung cancer, and neuroblastoma. We evaluated the anti-cancer activity of the ALK inhibitor KRCA-0008 using ALCL cell lines that express NPM (nucleophosmin)-ALK.

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.

Effectiveness of Autologous Fat Graft in Treating Fecal Incontinence.

Purpose: The most common risk factor for fecal incontinence (FI) is obstetric injury. FI affects 1.4%-18% of adults.

The application of a vascular closure device for closing a gastrostomy opening used for procedural access.

Objective: To study the feasibility of applying the Perclose ProGlide vascular closure device (PPVCD) for closing a gastrostomy opening for procedural access in the swine stomach in order to prevent peritoneal leakage.

Methods: The study included four experimental groups: one manual suture ( = 10), two manual sutures ( = 10), one PPVCD suture ( = 10), and two PPVCD sutures ( = 5). In the two PPVCD sutures group, the "pre-close" technique was used.

Low bone mineral density predicts the formation of new syndesmophytes in patients with axial spondyloarthritis.

Background: This study aimed to investigate whether the presence of low bone mineral density (BMD) in patients with axial spondyloarthritis (axSpA) predicts formation of new syndesmophytes over 2 years.

Methods: One hundred and nineteen patients fulfilling the imaging arm of the Assessment of SpondyloArthritis International Society axSpA criteria were enrolled. All patients were under 50 years of age.

Zebrafish as a Screening Model for Testing the Permeability of Blood-Brain Barrier to Small Molecules.

The objective of this study was to evaluate the permeability of small molecules into the brain via the blood-brain barrier in zebrafish and to investigate the possibility of using this animal model as a screening tool during the early stages of drug discovery. Fifteen compounds were used to understand the permeation into the brain in zebrafish and mice. The ratio of brain-to-plasma concentration was compared between the two animal models.

Novel 2,4-diaminopyrimidines bearing fused tricyclic ring moiety for anaplastic lymphoma kinase (ALK) inhibitor.

In this study, a series of novel 2,4-diaminopyrimidines bearing fused tricyclic ring moiety was described for ALK inhibitor. The pyrazole, imidazole, 1,2,4-triazole, piperazine and phenanthridine moieties were employed at the 2-position of pyrimidine. Among the compounds synthesized, 28, 29, 36, and 42 showed promising anti-ALK activities in enzymatic- and cell-based assays.

Early Experience With a Partial Stapled Hemorrhoidopexy for Treating Patients With Grades III-IV Prolapsing Hemorrhoids.

Purpose: Circular stapled hemorrhoidopexy (CSH) is widely used to treat patients with grades III-IV hemorrhoids because of less pain and short hospital stay. However, this procedure is associated with some complications, such as urge to defecate, anal stenosis, staple line dehiscence, abscess and sepsis. To avoid these complications, surgeons perform a partial stapled hemorrhoidopexy (PSH).