TY  - JOUR
A1  - Schlevogt, Bernhard
A1  - Boeker, Klaus H. W.
A1  - Mauss, Stefan
A1  - Klinker, Hartwig
A1  - Heyne, Renate
A1  - Link, Ralph
A1  - Simon, Karl-Georg
A1  - Sarrazin, Christoph
A1  - Serfert, Yvonne
A1  - Manns, Michael P.
A1  - Wedemeyer, Heiner
T1  - Weight gain after interferon-free treatment of chronic hepatitis C — results from the German Hepatitis C-Registry (DHC-R)
JF  - Biomedicines
N2  - Chronic hepatitis C can be treated very effectively with direct-acting antivirals (DAA) with only minor side effects compared to an interferon-containing treatment regimen. The significance of metabolic comorbidities after HCV cure is not well defined. This study aims to investigate short- and long-term weight change of patients receiving interferon-free antiviral treatment for chronic hepatitis C. The German Hepatitis C-registry (DHC-R) is a national multicenter real-world cohort. A total of 5111 patients were followed prospectively after DAA treatment for up to 3 years. Weight change compared to baseline was analyzed at end of treatment and at years 1, 2, and 3 after completion of antiviral therapy. Regression analysis was performed to identify baseline predictors for weight change. While there was no relevant mean weight change (−0.2 kg, SD 4.3 kg) at the end of antiviral treatment, weight started to increase during long-term follow-up reaching +1.7 kg (SD 8.0 kg, p < 0.001) compared to baseline at 3 years (follow-up year 3, FU3) after completion of antiviral therapy. 48%, 31%, and 22% of patients had a weight gain greater than 1, 3, and 5 kg at FU3, respectively. During follow-up, a body mass index (BMI) <30 proved to be the only consistent predictor for weight gain. DAA treatment is followed by a substantial weight gain (+3 kg or more) in one-third of the patients during long-term follow-up. Non-obese patients seemed to be most vulnerable to weight gain. The body compartment involved in weight gain as well as the mechanism of weight gain remain to be elucidated.
KW  - chronic hepatitis C
KW  - direct-acting antivirals
KW  - interferon-free
KW  - HCV cure
KW  - weight gain
KW  - German Hepatitis C-Registry
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-248476
SN  - 2227-9059
VL  - 9
IS  - 10
ER  - 
TY  - JOUR
A1  - Batool, Farwa
A1  - Saeed, Muhammad
A1  - Saleem, Hafiza Nosheen
A1  - Kirschner, Luisa
A1  - Bodem, Jochen
T1  - Facile synthesis and in vitro activity of N-substituted 1,2-benzisothiazol-3(2H)-ones against dengue virus NS2BNS3 protease
JF  - Pathogens
N2  - Several new N-substituted 1,2-benzisothiazol-3(2H)-ones (BITs) were synthesised through a facile synthetic route for testing their anti-dengue protease inhibition. Contrary to the conventional multistep synthesis, we achieved structurally diverse BITs with excellent yields using a two-step, one-pot reaction strategy. All the synthesised compounds were prescreened for drug-like properties using the online Swiss Absorption, Distribution, Metabolism and Elimination (SwissADME) model, indicating their favourable pharmaceutical properties. Thus, the synthesised BITs were tested for inhibitory activity against the recombinant dengue virus serotype-2 (DENV-2) NS2BNS3 protease. Dose–response experiments and computational docking analyses revealed that several BITs bind to the protease in the vicinity of the catalytic triad with IC\(_{50}\) values in the micromolar range. The DENV2 infection assay showed that two BITs, 2-(2-chlorophenyl)benzo[d]isothiazol-3(2H)-one and 2-(2,6-dichlorophenyl)benzo[d]isothiazol-3(2H)-one, could suppress DENV replication and virus infectivity. These results indicate the potential of BITs for developing new anti-dengue therapeutics.
KW  - dengue virus
KW  - direct-acting antivirals
KW  - 1,2-benzisothiazolinone
KW  - drug discovery
KW  - infectivity assays
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236605
SN  - 2076-0817
VL  - 10
IS  - 4
ER  -