Whitefield News

File includes: January 2016 Volume 3, Issue 7 February 2016 Volume 3, Issue 8 March 2016 Volume 3, Issue 9 April 2016 Volume 3, Issue 10 May 2016 Volume 3, Issue 11 June 2016 Volume 3, Issue 12 July 2016 Volume 4, Issue 1 August 2016 Volume 4, Issue 2 September 2016, Volume 4, Issue 3 October 2016, Volume 4, Issue 4 November 2016, Volume 4, Issue 5 December 2016, Volume 4, Issue

Acriflavine, a clinically approved drug, inhibits SARS-CoV-2 and other betacoronaviruses

The COVID-19 pandemic caused by SARS-CoV-2 has been socially and economically devastating. Despite an unprecedented research effort and available vaccines, effective therapeutics are still missing to limit severe disease and mortality. Using high-throughput screening, we identify acriflavine (ACF) as a potent papain-like protease (PLpro) inhibitor. NMR titrations and a co-crystal structure confirm that acriflavine blocks the PLpro catalytic pocket in an unexpected binding mode. We show that the drug inhibits viral replication at nanomolar concentration in cellular models, in vivo in mice and ex vivo in human airway epithelia, with broad range activity against SARS-CoV-2 and other betacoronaviruses. Considering that acriflavine is an inexpensive drug approved in some countries, it may be immediately tested in clinical trials and play an important role during the current pandemic and future outbreaks. © 2021 The Author

Autologous Stem Cell Transplantation in Common Variable Immunodeficiency: A Case of Successful Treatment of Severe Refractory Autoimmune Encephalitis

Common variable immunodeficiency (CVID) is the most common primary immunodeficiency in adults. It is associated with hypogammaglobulinemia, recurring infections and autoimmune phenomena. Treatment includes immunoglobulin substitution and immunosuppressants. Autoimmune neurological manifestations of CVID are rare and occur predominantly as granulomatous disease. We report the case of a 35-year-old woman with CVID who developed autoimmune encephalitis as demonstrated by double cerebral biopsy. Infectious or malignant causes could be excluded. Despite intensive immunosuppressive therapy with common regimens no significant improvement could be achieved. Ultimately, an autologous hematopoietic stem cell transplantation (HSCT) was performed, resulting in lasting complete remission of the encephalitis. To our knowledge, this is the first report of refractory autoimmune phenomena in CVID treated by autologous HSCT

Immunological Adverse Events After Autologous Hematopoietic Stem Cell Transplantation in Systemic Sclerosis Patients

Autologous hematopoietic stem cell transplantation (aHSCT) represents an effective treatment for systemic sclerosis (SSc), but it also can cause immunological adverse events (iAEs). Therefore, we aimed to determine the frequency of iAEs [engraftment syndrome (ES) and secondary autoimmune disorder (sAD)] and to identify potential risk factors for their development in a retrospective analysis on 22 patients similarly transplanted due to SSc. While nine patients (41%) suffered from ESs, seven sADs occurred in six patients (27%). Patients who developed ES were older in our cohort (52.45 vs. 42.58 years, p = .0433, Cohen’s d = 0.86), and cardiac involvement by SSc was associated with development of ES (OR = 40.11, p = .0017). Patients with manifestation of sAD had a higher modified Rodnan skin score (mRSS) reduction after aHSCT (90.50% vs. 60.00%, p = .0064, r = .65). Thus, IAEs are common after aHSCT for SSc and can occur in different stages during and after aHSCT with characteristic clinical manifestations. Good cutaneous response after aHSCT might be considered as a risk factor for sAD, and higher age at aHSCT and cardiac involvement might be considered as risk factors for the development of ES

Apps in der Rheumatologie

Background!#!Digital health applications/apps (DiGA) are entering many medical disciplines and have the potential to revolutionize patient care. In rheumatology, the use for axial spondyloarthritis (axSpA) would be conceivable in the form of an exercise app. Therefore, a representative survey among axSpA patients was conducted to determine the need for an axSpA exercise app.!##!Materials and methods!#!An anonymous online survey among axSpA patients of the German Bechterew's Disease Association was conducted using a questionnaire; data were analysed using Excel, and GraphPad Prism.!##!Results!#!Four hundred and thirty-five axSpA patients participated in the survey. Eighty-four percent of the participants responded that there is a need to develop an axSpA-specific exercise app, and the same proportion want to use it. Patients under 60 years, patients under 60 years on biologics or Janus kinase inhibitor therapy, and patients with frequent back pain reported a greater need than their respective control subgroups (p < 0.001 in each case).!##!Conclusion!#!The development of an exercise app for axSpA is considered necessary by a large proportion of the patients; younger and more intensively treated patients appear to have a greater need

Synthesis and study of cytotoxic activity of 1,2,4-trioxane- and egonol-derived hybrid molecules against Plasmodium falciparum and multidrug-resistant human leukemia cells

WOS: 000333775600039PubMed ID: 24561670Malaria and cancer cause the death of millions of people every year. To combat these two diseases, it is important that new pharmaceutically active compounds have the ability to overcome multidrug resistance in cancer and Plasmodium falciparum strains. In search of effective anti-cancer and anti-malaria hybrids that possess improved properties compared to their parent compounds, a series of novel 1,2,4-trioxane-based hybrids incorporating egonol and/or ferrocene fragments were synthesized and tested in vitro against P. falciparum strains, CCRF CEM cells and the multidrug-resistant P-glycoprotein-over-expressing CEM/ADR5000 cells. The most active compounds against P. falciparum strains were artesunic acid homodimers 12 and 13 (IC50 of 0.32 and 0.30 nM, respectively), whereas novel hybrids 7 (1,2,4-trioxane ferrocene egonol), 9 (1,2,4-trioxane ferrocene) and 11 (artesunic acid egonol) showed a remarkable cytotoxicity toward CCRF CEM cells (IC50 of 0.07, 0.25 and 0.18 mu M, respectively). A cooperative and synergistic effect of the three moieties 1,2,4-trioxane, ferrocene and egonol in hybrid molecule 7 is significant and is obviously stronger than in hybrids 9 (1,2,4-trioxane ferrocene) and 11 (artesunic acid egonol), which comprises of only two of the three considered parent compounds. Interestingly, hybrid 9 containing a 1,2,4-trioxane and a ferrocene fragment has shown to be the most effective among the studied hybrids against the tested multidrug-resistant leukemia CEM/ADR5000 cells (IC50 of 0.57 mu M) and possesses a degree of cross-resistance of 2.34. (C) 2014 Elsevier Masson SAS. All rights reserved.Dr. Hertha & Helmut Schmauser-Stiftung; German Academic Exchange Service DAADDeutscher Akademischer Austausch Dienst (DAAD)We are grateful to the "Dr. Hertha & Helmut Schmauser-Stiftung" for research support. We thank Professor Andriy Mokhir for pointing out ferrocene-based anti-cancer agents. We thank Mr. Bhasem Gharib (University of Erlangen-Nuremberg, Germany) for the supply with ferrocene monocarboxylic acid and ferrocene dicarboxylic acid.; Financial support by the German Academic Exchange Service DAAD (doctoral research fellowship for Aysun capci Karagoz) is gratefully acknowledged