-
Journal of Medical Case Reports Nov 2021In recent years, numerous studies have reported the development or exacerbation of sarcoidosis due to interferon therapy. However, ocular lesions rarely present as... (Review)
Review
BACKGROUND
In recent years, numerous studies have reported the development or exacerbation of sarcoidosis due to interferon therapy. However, ocular lesions rarely present as initial symptoms. Herein, we describe a rare case of interferon-α-induced sarcoidosis with uveitis as the initial symptom, and present a review of the relevant literature.
CASE PRESENTATION
This case involved a 62-year-old-Japanese woman with a history of a combination treatment of pegylated interferon-α-2a, ribavirin, and simeprevir, after which she developed granulomatous panuveitis. She was subsequently diagnosed with sarcoidosis following histological examination of skin biopsy specimens. In addition to reporting this case, we performed a literature review of 27 cases (24 case reports) of histopathologically diagnosed interferon-α-induced sarcoidosis published between January 2009 and November 2018.
CONCLUSIONS
Among the reviewed cases, 23 (85.1%) cases developed skin lesions and 19 (70.1%) had lung lesions. Only three cases (11.1%) had accompanying eye lesions. Interferon-α therapy was discontinued in 16 cases (52.9%), and the majority exhibited improvement after systemic corticosteroid treatment. There are few reported cases of interferon-α-induced sarcoidosis with uveitis as the initial symptom. However, if uveitis develops during or after interferon-α treatment, it might represent an initial symptom of interferon-α-induced sarcoidosis, as observed in the present case.
Topics: Antiviral Agents; Female; Humans; Middle Aged; Panuveitis; Ribavirin; Sarcoidosis; Uveitis
PubMed: 34836557
DOI: 10.1186/s13256-021-03181-x -
PloS One 2023The pandemic of COVID-19 is a severe threat to human life and the global economy. Despite the success of vaccination efforts in reducing the spread of the virus, the...
The pandemic of COVID-19 is a severe threat to human life and the global economy. Despite the success of vaccination efforts in reducing the spread of the virus, the situation remains largely uncontrolled due to the random mutation in the RNA sequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which demands different variants of effective drugs. Disease-causing gene-mediated proteins are usually used as receptors to explore effective drug molecules. In this study, we analyzed two different RNA-Seq and one microarray gene expression profile datasets by integrating EdgeR, LIMMA, weighted gene co-expression network and robust rank aggregation approaches, which revealed SARS-CoV-2 infection causing eight hub-genes (HubGs) including HubGs; REL, AURKA, AURKB, FBXL3, OAS1, STAT4, MMP2 and IL6 as the host genomic biomarkers. Gene Ontology and pathway enrichment analyses of HubGs significantly enriched some crucial biological processes, molecular functions, cellular components and signaling pathways that are associated with the mechanisms of SARS-CoV-2 infections. Regulatory network analysis identified top-ranked 5 TFs (SRF, PBX1, MEIS1, ESR1 and MYC) and 5 miRNAs (hsa-miR-106b-5p, hsa-miR-20b-5p, hsa-miR-93-5p, hsa-miR-106a-5p and hsa-miR-20a-5p) as the key transcriptional and post-transcriptional regulators of HubGs. Then, we conducted a molecular docking analysis to determine potential drug candidates that could interact with HubGs-mediated receptors. This analysis resulted in the identification of top-ranked ten drug agents, including Nilotinib, Tegobuvir, Digoxin, Proscillaridin, Olysio, Simeprevir, Hesperidin, Oleanolic Acid, Naltrindole and Danoprevir. Finally, we investigated the binding stability of the top-ranked three drug molecules Nilotinib, Tegobuvir and Proscillaridin with the three top-ranked proposed receptors (AURKA, AURKB, OAS1) by using 100 ns MD-based MM-PBSA simulations and observed their stable performance. Therefore, the findings of this study might be useful resources for diagnosis and therapies of SARS-CoV-2 infections.
Topics: Humans; COVID-19; Transcriptome; SARS-CoV-2; Molecular Docking Simulation; Aurora Kinase A; Proscillaridin; MicroRNAs; Gene Regulatory Networks; Biomarkers; Genomics; COVID-19 Testing
PubMed: 36913345
DOI: 10.1371/journal.pone.0281981 -
The Libyan Journal of Medicine Dec 2021Despite the high efficacy and safety of direct-acting antivirals against hepatitis C virus shown in clinical trials, treatment failures continue to occur. Our aim was... (Observational Study)
Observational Study
Despite the high efficacy and safety of direct-acting antivirals against hepatitis C virus shown in clinical trials, treatment failures continue to occur. Our aim was to establish the effectiveness of these drugs in routine clinical practice, as well as to determine factors that could influence the response to the treatment. Single-center, observational, retrospective study. Clinical, virological and pharmacotherapeutic variables were registered at baseline. Adverse drug reactions that occurred were recorded until week 24 of follow-up. Achievement of sustained virologic response was also recorded. Univariate and multivariate analysis were done to determine factors of response. A total of 333 treatment regimens corresponding to 330 different patients were evaluated. Sustained virologic response rate was 94.6% [95%CI: 91.6-96.6%]. 67.9% of the patients experienced adverse drugs reactions (92.2% were grade 1). The univariate analysis identified a higher baseline of platelets, albumin and total cholesterol as predictive factors of sustained virologic response (p < 0.05). Presence of diabetes and complications related to liver disease (splenomegaly, portal hypertension, portal hypertensive gastropathy), body mass index ≥30, greater liver fibrosis, receiving simeprevir and higher baseline levels of glucose, aspartate-aminotransferase, alanine-aminotransferase and alkaline-phosphatase, have been identified as predictive factors of non-response (p < 0.05). The multivariate analysis detected the following independent factors of non-response: body mass index ≥30 and presence of complications related to liver disease. The effectiveness and safety of direct-acting antivirals against hepatitis C virus have been maintained in routine clinical practice. Further research on predictive factors of response is required in order to develop more reliable and reproducible predictive models.
Topics: Antiviral Agents; Drug Therapy, Combination; Hepacivirus; Hepatitis C, Chronic; Humans; Pharmaceutical Preparations; Retrospective Studies; Treatment Outcome
PubMed: 34308801
DOI: 10.1080/19932820.2021.1949797 -
Global Health & Medicine Aug 2022It is well-known that sustained virological response (SVR) by interferon (IFN)-based therapy against hepatitis C virus (HCV) infection reduced the incidence of...
It is well-known that sustained virological response (SVR) by interferon (IFN)-based therapy against hepatitis C virus (HCV) infection reduced the incidence of hepatocellular carcinoma (HCC). However, whether IFN-free direct-acting antivirals reduce the risk of HCC is controversial. Therefore, this study aims to compare the incidence of HCC after the achievement of SVR between sofosbuvir combined with ledipasvir (SOF/LDV) and simeprevir with pegylated interferon plus ribavirin (Sim+IFN). Japanese patients with HCV infection (genotype 1) who achieved SVR between January 2013 and December 2014 by SOF/LDV (NCT01975675, = 320) or Sim+IFN (000015933, = 289) therapy in two nationwide, multicenter, phase III studies were prospectively monitored for the development of HCC by ultrasonography for 5 years after the end of treatment (EOT). No HCC was detected before the treatment. HCC was detected in 9 and 7 patients in the SOF/LDV and the Sim+IFN group in 5 years, respectively. The cumulative incidences of HCC rates 1, 3, and 5 years after EOT were similar between the two groups (1.5%, 2.7%, and 3.2% for the SOF/LDV and 1.8%, 2.8%, and 3.0% for the Sim+IFN group, respectively). No HCC was developed 3.5 years after EOT. Interestingly, a retrospective careful review of imaging taken before therapy revealed hepatic nodules in 50% of HCC patients, suggesting HCC was pre-existed before therapy. In conclusion, we could not find any differences in the incidence of HCC after the HCV eradication between the two therapeutic regimens, suggesting no enhancement of HCC development by DAA.
PubMed: 36119787
DOI: 10.35772/ghm.2022.01026 -
Journal of Diabetes and Metabolic... Dec 2020Recently, the world has been dealing with a new type of coronavirus called COVID-19 that in terms of symptoms is similar to the SARS coronavirus. Unfortunately,...
PURPOSE
Recently, the world has been dealing with a new type of coronavirus called COVID-19 that in terms of symptoms is similar to the SARS coronavirus. Unfortunately, researchers could not find a registered therapy to treat the infection related to the virus yet. Regarding the fact that drug repurposing is a good strategy for epidemic viral infection, we applied the drug repurposing strategy using virtual screening to identify therapeutic options for COVID-19. For this purpose, five proteins of COVID-19 (3-chymotrypsin-like protease (3CLpro), Papain-Like protease (PLpro), cleavage site, HR1 and RBD in Spike protein) were selected as target proteins for drug repositioning.
METHODS
First, five proteins of COVID-19 were built by homology modeling. Then FDA-approved drugs (2471 drugs) were screened against cleavage site and RBD in Spike protein via virtual screening. One hundred and twenty-eight FDA-approved drugs with the most favorable free-binding energy were attached to the cleavage site and RBD in Spike protein. Of these 128 drugs, 18 drugs have either been used currently as antiviral or have been reported to possess antiviral effects. Virtual screening was then performed for the 18 selected drugs with ACE2, 3CLpro and PLpro and HR1 and TMPRSS2.
RESULTS
According to the results, glecaprevir, paritaprevir, simeprevir, ledipasvir, glycyrrhizic acid, TMC-310911, and hesperidin showed highly favorably free binding energies with all tested target proteins.
CONCLUSION
The above-mentioned drugs can be regarded as candidates to treat COVID-19 infections, but further study on the efficiency of these drugs is also necessary.
PubMed: 32837954
DOI: 10.1007/s40200-020-00546-9 -
World Journal of Gastroenterology Jan 2020Hepatitis C virus (HCV) infection and its consequent complications are undeniably a public health burden worldwide, particularly in Egypt. Emerging evidence suggests... (Observational Study)
Observational Study
Assessment of lncRNA GAS5, lncRNA HEIH, lncRNA BISPR and its mRNA BST2 as serum innovative non-invasive biomarkers: Recent insights into Egyptian patients with hepatitis C virus type 4.
BACKGROUND
Hepatitis C virus (HCV) infection and its consequent complications are undeniably a public health burden worldwide, particularly in Egypt. Emerging evidence suggests that many lncRNAs have relevant roles in viral infections and antiviral responses.
AIM
To investigate the expression profiles of circulating lncRNAGAS5, lncRNAHEIH, lncRNABISPR and mRNABST2 in naïve, treated and relapsed HCV Egyptian patients, to elucidate relation to HCV infection and their efficacy as innovative biomarkers for the diagnosis and prognosis of HCV GT4.
METHODS
One hundred and thirty HCV-infected Egyptian patients and 20 healthy controls were included in this study. Serum lncRNAs and mRNABST2 were measured using quantitative real-time polymerase chain reaction (qRT-PCR).
RESULTS
Our results indicated that serum lncRNAGAS5 and LncRNABISPR were upregulated, whereas mRNA BST2 and LncRNA HEIH were downregulated in naïve patients. In contrast, HCV patients treated with sofosbuvir and simeprevir; with sofosbuvir and daclatasvir; or with sofosbuvir, daclatasvir and ribavirin exhibited lower levels of lncRNAGAS5 and lncRNABISPR with higher mRNABST2 compared to naïve patients. Notably, patients relapsed from sofosbuvir and simeprevir showed higher levels of these lncRNAs with lower mRNABST2 compared to treated patients. LncRNAGAS5 and lncRNABISPR were positively correlated with viral load and ALT at < 0.001, whereas mRNABST2 was negatively correlated with viral load at < 0.001 and ALT at < 0.05. Interestingly, a significant positive correlation between lncRNA HEIH and AFP was observed at < 0.001.
CONCLUSION
Differential expression of these RNAs suggests their involvement in HCV pathogenesis or antiviral response and highlights their promising roles in diagnosis and prognosis of HCV.
Topics: Adult; Antigens, CD; Antiviral Agents; Biomarkers; Case-Control Studies; Cell-Free Nucleic Acids; Down-Regulation; Drug Therapy, Combination; Egypt; Female; GPI-Linked Proteins; Gene Expression Profiling; Healthy Volunteers; Hepacivirus; Hepatitis C; Humans; Male; Middle Aged; RNA, Long Noncoding; RNA, Messenger; Real-Time Polymerase Chain Reaction; Up-Regulation
PubMed: 31988583
DOI: 10.3748/wjg.v26.i2.168 -
Jornal Brasileiro de Nefrologia 2021In addition to liver disease, the hepatitis C virus (HCV) has been associated with autoimmune phenomena, such as mixed cryoglobulin and glomerulonephritis (GN). Until...
In addition to liver disease, the hepatitis C virus (HCV) has been associated with autoimmune phenomena, such as mixed cryoglobulin and glomerulonephritis (GN). Until recently, both chronic hepatitis and HCV extra-hepatic manifestations were treated with peg-interferon plus ribavirin, however these drugs presented low efficacy and induced severe side effects. Nowadays, the HCV chronic hepatitis has been treated with direct acting antivirals (DAA), but studies on the DAA therapy for HCV-associated glomerulonephritis are scarce. Here, we describe two cases of HCV-associated glomerulonephritis that were treated with DAAs. In these two cases, previously experienced to peg-interferon plus ribavirin, the sofosbuvir plus simeprevir therapy was effective, without significant side effects, and interrupted the evolution of at least 20 years of both hepatic and renal diseases. These cases join the seven previously described cases that were treated with this DAAs association.
Topics: Antiviral Agents; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Pharmaceutical Preparations
PubMed: 33022028
DOI: 10.1590/2175-8239-JBN-2019-0165 -
World Journal of Hepatology Jan 2022Hepatitis C virus (HCV) treatment has undergone major changes in recent years. Previous interferon-based therapies have been replaced by oral direct-acting antivirals...
BACKGROUND
Hepatitis C virus (HCV) treatment has undergone major changes in recent years. Previous interferon-based therapies have been replaced by oral direct-acting antivirals (DAA) regimens, with high sustained virologic response (SVR) rates, and a lower incidence of adverse events (AEs).
AIM
To evaluate the efficacy and safety of DAAs for HCV treatment in subjects from two tertiary university centers in Brazil.
METHODS
This is a multicenter retrospective cohort study of 532 patients with chronic hepatitis C (CHC), undergoing treatment with interferon-free regimens from November 2015 to November 2019. The therapeutic regimen was defined by the current Brazilian guidelines for HCV management at the time of treatment. Demographic, anthropometric, clinical, and laboratory variables were evaluated. SVRs were assessed at 12 to 24 wk after therapy by intention-to-treat (ITT), and modified ITT (m-ITT) analysis. AEs and serious adverse events (SAEs) were registered. In the statistical analysis, a value of < 0.05 was considered significant.
RESULTS
The mean age was 56.88 years, with 415 (78.5%) being HCV genotype 1, followed by genotype 3 (20.1%). Moreover, 306 (57.5%) subjects had cirrhosis, and a third of them had decompensated cirrhosis. Sofosbuvir (SOF) plus daclatasvir ± ribavirin was the most frequently used treatment (66.9%), followed by SOF plus simeprevir (21.2%). The overall ITT SVR was 92.6% (493/532), while the m-ITT SVR was 96.8% (493/509). Variables associated with treatment failure ITT evaluation were hepatic encephalopathy (OR: 4.320; 95%CI: 1.920-9.721, = 0.0004), presence of esophageal varices (OR: 2.381; 95%CI: 1.137-4.988, = 0.0215), previous portal hypertensive bleeding (OR: 2.756; 95%CI: 1.173-6.471, = 0.02), higher model for end-stage liver disease scores (OR: 1.143, 95%CI: 1.060-1.233, = 0.0005), lower serum albumin levels (OR: 0.528, 95%CI: 0.322-0.867, = 0.0115), higher serum creatinine (OR: 1.117, 95%CI: 1.056-1.312, = 0.0033), and international normalized ratio (INR) levels (OR: 5.542, 95%CI: 2.023-15.182, = 0.0009). AEs were reported in 41.1% (211/514) of patients, and SAEs in 3.7%. The female gender, higher body mass index, esophageal varices, higher INR values, and longer treatment duration were independently associated with AE occurrence.
CONCLUSION
Treatment with oral DAAs attains a high SVR rate, with fewer SAEs in a real-life cohort of subjects with CHC, from two tertiary university centers in Brazil.
PubMed: 35126848
DOI: 10.4254/wjh.v14.i1.195 -
Scientific Reports Mar 2023Some recent studies showed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and idiopathic pulmonary fibrosis (IPF) disease might stimulate...
Some recent studies showed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and idiopathic pulmonary fibrosis (IPF) disease might stimulate each other through the shared genes. Therefore, in this study, an attempt was made to explore common genomic biomarkers for SARS-CoV-2 infections and IPF disease highlighting their functions, pathways, regulators and associated drug molecules. At first, we identified 32 statistically significant common differentially expressed genes (cDEGs) between disease (SARS-CoV-2 and IPF) and control samples of RNA-Seq profiles by using a statistical r-package (edgeR). Then we detected 10 cDEGs (CXCR4, TNFAIP3, VCAM1, NLRP3, TNFAIP6, SELE, MX2, IRF4, UBD and CH25H) out of 32 as the common hub genes (cHubGs) by the protein-protein interaction (PPI) network analysis. The cHubGs regulatory network analysis detected few key TFs-proteins and miRNAs as the transcriptional and post-transcriptional regulators of cHubGs. The cDEGs-set enrichment analysis identified some crucial SARS-CoV-2 and IPF causing common molecular mechanisms including biological processes, molecular functions, cellular components and signaling pathways. Then, we suggested the cHubGs-guided top-ranked 10 candidate drug molecules (Tegobuvir, Nilotinib, Digoxin, Proscillaridin, Simeprevir, Sorafenib, Torin 2, Rapamycin, Vancomycin and Hesperidin) for the treatment against SARS-CoV-2 infections with IFP diseases as comorbidity. Finally, we investigated the resistance performance of our proposed drug molecules compare to the already published molecules, against the state-of-the-art alternatives publicly available top-ranked independent receptors by molecular docking analysis. Molecular docking results suggested that our proposed drug molecules would be more effective compare to the already published drug molecules. Thus, the findings of this study might be played a vital role for diagnosis and therapies of SARS-CoV-2 infections with IPF disease as comorbidity risk.
Topics: Humans; COVID-19; SARS-CoV-2; Molecular Docking Simulation; Drug Repositioning; Idiopathic Pulmonary Fibrosis; Computational Biology
PubMed: 36949176
DOI: 10.1038/s41598-023-31276-6 -
Methods (San Diego, Calif.) Jul 2022For the last two years, the COVID-19 pandemic has continued to bring consternation on most of the world. According to recent WHO estimates, there have been more than 5.6...
For the last two years, the COVID-19 pandemic has continued to bring consternation on most of the world. According to recent WHO estimates, there have been more than 5.6 million deaths worldwide. The virus continues to evolve all over the world, thus requiring both vigilance and the necessity to find and develop a variety of therapeutic treatments, including the identification of specific antiviral drugs. Multiple studies have confirmed that SARS-CoV-2 utilizes its membrane-bound spike protein to recognize human angiotensin-converting enzyme 2 (ACE2). Thus, preventing spike-ACE2 interactions is a potentially viable strategy for COVID-19 treatment as it would block the virus from binding and entering into a host cell. This work aims to identify potential drugs using an in silico approach. Molecular docking was carried out on both approved drugs and substances previously tested in vivo. This step was followed by a more detailed analysis of selected ligands by molecular dynamics simulations to identify the best molecules that thwart the ability of the virus to interact with the ACE2 receptor. Because the SARS-CoV-2 virus evolves rapidly due to a plethora of immunocompromised hosts, the compounds were tested against five different known lineages. As a result, we could identify substances that work well on individual lineages and those showing broader efficacy. The most promising candidates among the currently used drugs were zafirlukast and simeprevir with an average binding affinity of -22 kcal/mol for spike proteins originating from various lineages. The first compound is a leukotriene receptor antagonist that is used to treat asthma, while the latter is a protease inhibitor used for hepatitis C treatment. From among the in vivo tested substances that concurrently exhibit promising free energy of binding and ADME parameters (indicating a possible oral administration) we selected the compound BDBM50136234. In conclusion, these molecules are worth exploring further by in vitro and in vivo studies against SARS-CoV-2.
Topics: Angiotensin-Converting Enzyme 2; Antiviral Agents; Drug Repositioning; Humans; Molecular Docking Simulation; Molecular Dynamics Simulation; Pandemics; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35167916
DOI: 10.1016/j.ymeth.2022.02.004