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1.
Viruses ; 14(1)2021 12 21.
Article in English | MEDLINE | ID: covidwho-1580416

ABSTRACT

Coronavirus disease 2019 (COVID-19) has claimed the lives of millions of people worldwide since it first emerged. The impact of the COVID-19 pandemic on public health and the global economy has highlighted the medical need for the development of broadly acting interventions against emerging viral threats. Galidesivir is a broad-spectrum antiviral compound with demonstrated in vitro and in vivo efficacy against several RNA viruses of public health concern, including those causing yellow fever, Ebola, Marburg, and Rift Valley fever. In vitro studies have shown that the antiviral activity of galidesivir also extends to coronaviruses. Herein, we describe the efficacy of galidesivir in the Syrian golden hamster model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Treatment with galidesivir reduced lung pathology in infected animals compared with untreated controls when treatment was initiated 24 h prior to infection. These results add to the evidence of the applicability of galidesivir as a potential medical intervention for a range of acute viral illnesses, including coronaviruses.


Subject(s)
Adenine/analogs & derivatives , Adenosine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Pyrrolidines/therapeutic use , SARS-CoV-2/drug effects , Adenine/pharmacology , Adenine/therapeutic use , Adenosine/pharmacology , Adenosine/therapeutic use , Animals , Antiviral Agents/pharmacology , COVID-19/pathology , COVID-19/virology , Cell Line , Cricetinae , Disease Models, Animal , Humans , Lung/drug effects , Lung/pathology , Lung/virology , Mesocricetus , Pyrrolidines/pharmacology , Viral Load/drug effects
2.
EBioMedicine ; 74: 103705, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1540597

ABSTRACT

BACKGROUND: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls. METHODS: 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection. FINDINGS: Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively. INTERPRETATION: The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity. FUNDING: Knut and Alice Wallenberg Foundation, the Swedish Research Council, Nordstjernan AB, Region Stockholm, Karolinska Institutet, and organizations for PID/CLL-patients in Sweden.


Subject(s)
/adverse effects , Immunocompromised Host/immunology , Immunogenicity, Vaccine/immunology , SARS-CoV-2/immunology , Adenine/adverse effects , Adenine/analogs & derivatives , Adenine/therapeutic use , Antibodies, Viral/blood , COVID-19/prevention & control , Female , Hematopoietic Stem Cell Transplantation , Humans , Immunotherapy, Adoptive , Leukemia, Lymphocytic, Chronic, B-Cell , Male , Middle Aged , Mycophenolic Acid/adverse effects , Mycophenolic Acid/therapeutic use , Organ Transplantation , Piperidines/adverse effects , Piperidines/therapeutic use , Primary Immunodeficiency Diseases/immunology , Prospective Studies , Seroconversion , Spike Glycoprotein, Coronavirus/immunology , Vaccination/adverse effects
3.
J Am Chem Soc ; 143(48): 20095-20108, 2021 12 08.
Article in English | MEDLINE | ID: covidwho-1531986

ABSTRACT

Chemical modifications of native proteins can affect their stability, activity, interactions, localization, and more. However, there are few nongenetic methods for the installation of chemical modifications at a specific protein site in cells. Here we report a covalent ligand directed release (CoLDR) site-specific labeling strategy, which enables the installation of a variety of functional tags on a target protein while releasing the directing ligand. Using this approach, we were able to label various proteins such as BTK, K-RasG12C, and SARS-CoV-2 PLpro with different tags. For BTK we have shown selective labeling in cells of both alkyne and fluorophores tags. Protein labeling by traditional affinity methods often inhibits protein activity since the directing ligand permanently occupies the target binding pocket. We have shown that using CoLDR chemistry, modification of BTK by these probes in cells preserves its activity. We demonstrated several applications for this approach including determining the half-life of BTK in its native environment with minimal perturbation, as well as quantification of BTK degradation by a noncovalent proteolysis targeting chimera (PROTAC) by in-gel fluorescence. Using an environment-sensitive "turn-on" fluorescent probe, we were able to monitor ligand binding to the active site of BTK. Finally, we have demonstrated efficient CoLDR-based BTK PROTACs (DC50 < 100 nM), which installed a CRBN binder onto BTK. This approach joins very few available labeling strategies that maintain the target protein activity and thus makes an important addition to the toolbox of chemical biology.


Subject(s)
Agammaglobulinaemia Tyrosine Kinase/chemistry , Fluorescent Dyes/chemistry , Ligands , Proto-Oncogene Proteins p21(ras)/antagonists & inhibitors , Adenine/analogs & derivatives , Adenine/chemistry , Adenine/metabolism , Agammaglobulinaemia Tyrosine Kinase/metabolism , Catalytic Domain , Coronavirus Papain-Like Proteases/chemistry , Coronavirus Papain-Like Proteases/metabolism , Half-Life , Humans , Piperidines/chemistry , Piperidines/metabolism , Proteolysis , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , Pyrimidines/chemistry , Pyrimidines/metabolism , SARS-CoV-2/enzymology
4.
Molecules ; 26(21)2021 Oct 26.
Article in English | MEDLINE | ID: covidwho-1488675

ABSTRACT

In the last two years, nucleosides analogues, a class of well-established bioactive compounds, have been the subject of renewed interest from the scientific community thanks to their antiviral activity. The COVID-19 global pandemic, indeed, spread light on the antiviral drug Remdesivir, an adenine C-nucleoside analogue. This new attention of the medical community on Remdesivir prompts the medicinal chemists to investigate once again C-nucleosides. One of the essential building blocks to synthetize these compounds is the D-(+)-ribono-1,4-lactone, but some mechanistic aspects linked to the use of different carbohydrate protecting groups remain unclear. Here, we present our investigations on the use of benzylidene as a ribonolactone protecting group useful in the synthesis of C-purine nucleosides analogues. A detailed 1D and 2D NMR structural study of the obtained compounds under different reaction conditions is presented. In addition, a molecular modeling study at the B3LYP/6-31G* level of theory with the SM8 solvation model for CHCl3 and DMSO to support the obtained results is used. This study allows for clarifying mechanistic aspects as the side reactions and structural rearrangements liked to the use of the benzylidene protecting group.


Subject(s)
Benzylidene Compounds/chemistry , Lactones/chemistry , Nucleosides/chemical synthesis , Ribose/analogs & derivatives , Adenine/analogs & derivatives , Antiviral Agents/chemistry , COVID-19/drug therapy , COVID-19/prevention & control , Humans , Lactones/chemical synthesis , Magnetic Resonance Spectroscopy , Models, Molecular , Nucleosides/metabolism , Purine Nucleosides , Ribose/chemical synthesis , Ribose/chemistry , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Stereoisomerism
5.
Sci Rep ; 11(1): 19998, 2021 10 07.
Article in English | MEDLINE | ID: covidwho-1462031

ABSTRACT

Understanding the effects of metabolism on the rational design of novel and more effective drugs is still a considerable challenge. To the best of our knowledge, there are no entirely computational strategies that make it possible to predict these effects. From this perspective, the development of such methodologies could contribute to significantly reduce the side effects of medicines, leading to the emergence of more effective and safer drugs. Thereby, in this study, our strategy is based on simulating the electron ionization mass spectrometry (EI-MS) fragmentation of the drug molecules and combined with molecular docking and ADMET models in two different situations. In the first model, the drug is docked without considering the possible metabolic effects. In the second model, each of the intermediates from the EI-MS results is docked, and metabolism occurs before the drug accesses the biological target. As a proof of concept, in this work, we investigate the main antiviral drugs used in clinical research to treat COVID-19. As a result, our strategy made it possible to assess the biological activity and toxicity of all potential by-products. We believed that our findings provide new chemical insights that can benefit the rational development of novel drugs in the future.


Subject(s)
Antiviral Agents/metabolism , COVID-19/drug therapy , Drug Discovery , SARS-CoV-2/drug effects , Adenine/adverse effects , Adenine/analogs & derivatives , Adenine/metabolism , Adenine/pharmacology , Adenosine/adverse effects , Adenosine/analogs & derivatives , Adenosine/metabolism , Adenosine/pharmacology , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/metabolism , Adenosine Monophosphate/pharmacology , Alanine/adverse effects , Alanine/analogs & derivatives , Alanine/metabolism , Alanine/pharmacology , Amides/adverse effects , Amides/metabolism , Amides/pharmacology , Antiviral Agents/adverse effects , Antiviral Agents/pharmacology , COVID-19/metabolism , Chloroquine/adverse effects , Chloroquine/analogs & derivatives , Chloroquine/metabolism , Chloroquine/pharmacology , Drug Design , Humans , Metabolic Networks and Pathways , Molecular Docking Simulation , Nitro Compounds/adverse effects , Nitro Compounds/metabolism , Nitro Compounds/pharmacology , Pyrazines/adverse effects , Pyrazines/metabolism , Pyrazines/pharmacology , Pyrrolidines/adverse effects , Pyrrolidines/metabolism , Pyrrolidines/pharmacology , Ribavirin/adverse effects , Ribavirin/metabolism , Ribavirin/pharmacology , SARS-CoV-2/metabolism , Thiazoles/adverse effects , Thiazoles/metabolism , Thiazoles/pharmacology
6.
Antiviral Res ; 195: 105180, 2021 11.
Article in English | MEDLINE | ID: covidwho-1415189

ABSTRACT

Galidesivir (BCX4430) is an adenosine nucleoside analog that is broadly active in cell culture against several RNA viruses of various families. This activity has also been shown in animal models of viral disease associated with Ebola, Marburg, yellow fever, Zika, and Rift Valley fever viruses. In many cases, the compound is more efficacious in animal models than cell culture activity would predict. Based on favorable data from in vivo animal studies, galidesivir has recently undergone evaluation in several phase I clinical trials, including against severe acute respiratory syndrome coronavirus 2, and as a medical countermeasure for the treatment of Marburg virus disease.


Subject(s)
Adenine/analogs & derivatives , Adenosine/analogs & derivatives , Antiviral Agents/pharmacology , Pyrrolidines/pharmacology , Adenine/pharmacology , Adenosine/pharmacology , Animals , Clinical Trials, Phase I as Topic , Drug Evaluation, Preclinical , Marburgvirus/drug effects , Nucleosides/analogs & derivatives , SARS-CoV-2/drug effects
7.
Int J Mol Sci ; 22(14)2021 Jul 16.
Article in English | MEDLINE | ID: covidwho-1389404

ABSTRACT

In the past few years, Bruton's tyrosine Kinase (Btk) has emerged as new target in medicinal chemistry. Since approval of ibrutinib in 2013 for treatment of different hematological cancers (as leukemias and lymphomas), two other irreversible Btk inhibitors have been launched on the market. In the attempt to overcome irreversible Btk inhibitor limitations, reversible compounds have been developed and are currently under evaluation. In recent years, many Btk inhibitors have been patented and reported in the literature. In this review, we summarized the (ir)reversible Btk inhibitors recently developed and studied clinical trials and preclinical investigations for malignancies, chronic inflammation conditions and SARS-CoV-2 infection, covering advances in the field of medicinal chemistry. Furthermore, the nanoformulations studied to increase ibrutinib bioavailability are reported.


Subject(s)
Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Protein Kinase Inhibitors/administration & dosage , Adenine/administration & dosage , Adenine/analogs & derivatives , Agammaglobulinaemia Tyrosine Kinase/metabolism , COVID-19/drug therapy , Chemistry, Pharmaceutical/methods , Drug Delivery Systems/methods , Hematologic Neoplasms/drug therapy , Humans , Inflammation/drug therapy , Neoplasms/drug therapy , Piperidines/administration & dosage , Protein-Tyrosine Kinases/antagonists & inhibitors , Pyrimidines/administration & dosage , SARS-CoV-2/drug effects
9.
Expert Rev Hematol ; 14(9): 819-830, 2021 09.
Article in English | MEDLINE | ID: covidwho-1349725

ABSTRACT

INTRODUCTION: Ibrutinib is a highly effective drug for patients with chronic lymphocytic leukemia (CLL), and is well tolerated even by older patients and those unfit to receive conventional immuno-chemotherapy. AREAS COVERED: The occurrence of adverse events was revealed as a major cause of ibrutinib failure in the real-world. Ibrutinib-induced lymphocytosis carries the risk of an untimely interruption of therapy because it may be misinterpreted as disease progression. In addition, drug interactions can worsen ibrutinib-associated toxicities by increasing the plasma concentration of ibrutinib. In this review, we present a case of major hemorrhage and atrial fibrillation (AF) during ibrutinib use and summarize the adverse events associated with ibrutinib. Furthermore, the practical management of ibrutinib-associated toxicities was covered with reference to a drug interaction mechanism. EXPERT OPINION: Clinicians should examine the prescribed drugs prior to ibrutinib initiation and carefully monitor toxicities while taking ibrutinib. A reduced dose of ibrutinib with the concurrent use of CYP3A inhibitors such as antifungal agents could be an attractive strategy to reduce toxicities and may confer financial benefits. Reducing unexpected toxicities is as significant as achieving treatment response in the era of life-long therapy with ibrutinib in patients with CLL.


Subject(s)
Adenine/analogs & derivatives , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Piperidines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Adenine/adverse effects , Adenine/pharmacology , Adenine/therapeutic use , Aged , COVID-19/complications , Disease Management , Drug Interactions , Drug-Related Side Effects and Adverse Reactions/etiology , Drug-Related Side Effects and Adverse Reactions/therapy , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Male , Piperidines/adverse effects , Piperidines/pharmacology , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/pharmacology
11.
Int J Mol Sci ; 22(13)2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1288906

ABSTRACT

Coronavirus disease (COVID)-19 is the leading global health threat to date caused by a severe acute respiratory syndrome coronavirus (SARS-CoV-2). Recent clinical trials reported that the use of Bruton's tyrosine kinase (BTK) inhibitors to treat COVID-19 patients could reduce dyspnea and hypoxia, thromboinflammation, hypercoagulability and improve oxygenation. However, the mechanism of action remains unclear. Thus, this study employs structure-based virtual screening (SBVS) to repurpose BTK inhibitors acalabrutinib, dasatinib, evobrutinib, fostamatinib, ibrutinib, inositol 1,3,4,5-tetrakisphosphate, spebrutinib, XL418 and zanubrutinib against SARS-CoV-2. Molecular docking is conducted with BTK inhibitors against structural and nonstructural proteins of SARS-CoV-2 and host targets (ACE2, TMPRSS2 and BTK). Molecular mechanics-generalized Born surface area (MM/GBSA) calculations and molecular dynamics (MD) simulations are then carried out on the selected complexes with high binding energy. Ibrutinib and zanubrutinib are found to be the most potent of the drugs screened based on the results of computational studies. Results further show that ibrutinib and zanubrutinib could exploit different mechanisms at the viral entry and replication stage and could be repurposed as potential inhibitors of SARS-CoV-2 pathogenesis.


Subject(s)
Adenine/analogs & derivatives , Drug Repositioning , Molecular Dynamics Simulation , Piperidines/chemistry , Protein Kinase Inhibitors/chemistry , Pyrazoles/chemistry , Pyrimidines/chemistry , Adenine/chemistry , Adenine/metabolism , Adenine/therapeutic use , Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Agammaglobulinaemia Tyrosine Kinase/metabolism , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/metabolism , Binding Sites , COVID-19/drug therapy , COVID-19/pathology , COVID-19/virology , Humans , Molecular Docking Simulation , Piperidines/metabolism , Piperidines/therapeutic use , Protein Kinase Inhibitors/metabolism , Protein Kinase Inhibitors/therapeutic use , Pyrazoles/metabolism , Pyrazoles/therapeutic use , Pyrimidines/metabolism , Pyrimidines/therapeutic use , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Serine Endopeptidases/chemistry , Serine Endopeptidases/metabolism , Thermodynamics , Viral Nonstructural Proteins/antagonists & inhibitors , Viral Nonstructural Proteins/metabolism
12.
Sci Adv ; 7(25)2021 06.
Article in English | MEDLINE | ID: covidwho-1276873

ABSTRACT

Infection by highly pathogenic coronaviruses results in substantial apoptosis. However, the physiological relevance of apoptosis in the pathogenesis of coronavirus infections is unknown. Here, with a combination of in vitro, ex vivo, and in vivo models, we demonstrated that protein kinase R-like endoplasmic reticulum kinase (PERK) signaling mediated the proapoptotic signals in Middle East respiratory syndrome coronavirus (MERS-CoV) infection, which converged in the intrinsic apoptosis pathway. Inhibiting PERK signaling or intrinsic apoptosis both alleviated MERS pathogenesis in vivo. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV induced apoptosis through distinct mechanisms but inhibition of intrinsic apoptosis similarly limited SARS-CoV-2- and SARS-CoV-induced apoptosis in vitro and markedly ameliorated the lung damage of SARS-CoV-2-inoculated human angiotensin-converting enzyme 2 (hACE2) mice. Collectively, our study provides the first evidence that virus-induced apoptosis is an important disease determinant of highly pathogenic coronaviruses and demonstrates that this process can be targeted to attenuate disease severity.


Subject(s)
Antiviral Agents/pharmacology , Apoptosis/drug effects , COVID-19/drug therapy , Coronavirus Infections/drug therapy , eIF-2 Kinase/metabolism , Adenine/analogs & derivatives , Adenine/pharmacology , Angiotensin-Converting Enzyme 2/genetics , Animals , Apoptosis/physiology , COVID-19/etiology , COVID-19/pathology , Cell Line , Coronavirus Infections/etiology , Coronavirus Infections/pathology , Dipeptidyl Peptidase 4/genetics , Epithelial Cells/virology , Female , Humans , Indoles/pharmacology , Lung/virology , Male , Mice, Transgenic , eIF-2 Kinase/antagonists & inhibitors , eIF-2 Kinase/genetics
15.
Mol Divers ; 26(1): 279-292, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1148916

ABSTRACT

Since the outbreak emerged in November 2019, no effective drug has yet been found against SARS-CoV-2. Repositioning studies of existing drug molecules or candidates are gaining in overcoming COVID-19. Antiviral drugs such as remdesivir, favipiravir, ribavirin, and galidesivir act by inhibiting the vital RNA polymerase of SARS-CoV-2. The importance of in silico studies in repurposing drug research is gradually increasing during the COVID-19 process. The present study found that especially ribavirin triphosphate and galidesivir triphosphate active metabolites had a higher affinity for SARS-CoV-2 RNA polymerase than ATP by molecular docking. With the Molecular Dynamics simulation, we have observed that these compounds increase the complex's stability and validate the molecular docking results. We also explained that the interaction of RNA polymerase inhibitors with Mg++, which is in the structure of NSP12, is essential and necessary to interact with the RNA strand. In vitro and clinical studies on these two molecules need to be increased.


Subject(s)
COVID-19 , Ribavirin , Adenine/analogs & derivatives , Adenosine/analogs & derivatives , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Amides , Antiviral Agents/chemistry , COVID-19/drug therapy , Drug Repositioning , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Pyrazines , Pyrrolidines , RNA, Viral , Ribavirin/pharmacology , SARS-CoV-2
19.
Int J Infect Dis ; 105: 274-276, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1085543

ABSTRACT

Immune modulation in COVID-19 is emerging as an important therapeutic strategy as increasing evidence suggests that inflammatory pathways are implicated in lung damage. Bruton tyrosine kinase inhibitors (BTKi), such as ibrutinib, are commonly used to treat indolent B-cell neoplasms and chronic graft-versus-host disease (GvHD). Given their potential to suppress pulmonary inflammatory cytokines and lessen acute lung injury, this could be applicable in the context of hospitalised COVID-19 patients. We describe an 81 year-old male receiving ibrutinib for Waldenstrom macroglobulinaemia (WM) who was hospitalised with COVID-19. On stopping the BTKi due to concerns of additional immunosuppression, he required non-invasive ventilation (NIV) in the intensive care unit (ICU) and demonstrated prompt clinical recovery when ibrutinib was reinstated. Continuing ibrutinib in patients with COVID-19 may be advantageous given its immunomodulatory properties and withdrawal of ibrutinib therapy may be detrimental. Further evidence is required to explore the potential therapeutic impact of BTKis and other immunomodulatory agents on the clinical course of COVID-19 as is currently being carried out in a number of clinical trials.


Subject(s)
Adenine/analogs & derivatives , Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , COVID-19/drug therapy , COVID-19/immunology , Piperidines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Adenine/therapeutic use , Aged, 80 and over , Humans , Immunomodulation , Male , SARS-CoV-2/immunology , Waldenstrom Macroglobulinemia/drug therapy , Waldenstrom Macroglobulinemia/immunology
20.
Ren Fail ; 43(1): 335-339, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1078673

ABSTRACT

The introduction of Bruton's tyrosine kinase inhibitor ibrutinib has made a significant progress in the treatment of chronic lymphocytic leukemia and other B-cell malignancies. Due to the reduction of cytokine release, it is effective in chronic graft-versus-host disease, and its use has also been suggested in autoimmune diseases and in prevention of COVID-19-associated lung damage. Despite this effect on the immune response, we report a severe hypersensitivity reaction in a 76-year-old male patient diagnosed with prolymphocytic leukemia. Four weeks after the ibrutinib start, non-oliguric acute kidney injury with proteinuria and microscopic hematuria developed and that was accompanied by lower limb purpuras and paresthesia. Renal biopsy revealed acute interstitial nephritis. Employing 1 mg/kg methylprednisolone administration, serum creatinine decreased from 365 µmol/L to 125 µmol/L at 11 days and the proteinuria-hematuria as well as the purpura, paresthesia resolved. Three months later at stabile eGFR of 56 ml/min/1.73 m2 methylprednisolone was withdrawn and a rituximab-venetoclax treatment was initiated without side effects. We conclude that despite the beneficial effect on cytokines response in Th1 direction, ibrutinib can cause acute interstitial nephritis. Early detection, discontinuation of ibrutinib, glucocorticoid administration may help to better preserve renal function, thereby lowering the risk of potential subsequent kidney injury.


Subject(s)
Acute Kidney Injury/chemically induced , Adenine/analogs & derivatives , Nephritis, Interstitial/chemically induced , Piperidines/adverse effects , Proteinuria/chemically induced , Acute Kidney Injury/drug therapy , Adenine/adverse effects , Aged , Cytokines/drug effects , Glucocorticoids/therapeutic use , Humans , Kidney/pathology , Leukemia, Prolymphocytic/drug therapy , Male , Nephritis, Interstitial/drug therapy , Protein Kinase Inhibitors , Proteinuria/drug therapy
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