Long-term renal outcome of Cryopyrin-associated periodic syndrome (CAPS) under anti-Interleukin-1 therapy.

Cryopyrin-associated periodic syndromes (CAPS) are orphan hereditary auto-inflammatory diseases with various phenotypes, including chronic kidney disease (CKD). Current therapies inhibit interleukin-1 (IL-1) to achieve clinical and serological remission; however, the effect on kidney involvement remains unclear. The objective of this study was to investigate the long-term efficacy of anti-IL-1 treatment with special emphasis on renal outcome. We retrospectively analysed clinical, genetic and laboratory data of patients with CAPS under anti-IL-1 therapy from a single-centre university outpatient clinic. Patients with CAPS (n = 28) were followed for a median of 11 (IQR 8.5-13) years. Four patients at various ages (19%), bearing the most common CAPS mutation R260W, had significant CKD at presentation. All affected patients were related; however, other family members with the same genetic variant did not develop CKD. While anti-IL-1 therapy was effective in lowering symptom burden and inflammatory parameters in all CAPS patients, two of the four individuals with significant CKD had persistent proteinuria and worsening kidney function. None of the patients without renal affection at therapy initiation developed relevant CKD in the follow-up period. We showed that in patients with CAPS: (1) CKD is a common complication; (2) renal involvement shows familial predisposition beyond the mutational status and is independent of age; (3) anti-IL-1 therapy results in sustained improvement of inflammatory parameters and symptom load and (4) may prevent development of CAPS-associated CKD but not affect kidney involvement when already present. Overall, early therapy initiation might sufficiently prevent renal disease manifestation and attenuate progression.

Marker-assisted introgression to improve the oleic acid content in the TMV 7 groundnut (Arachis hypogaea L.) variety suitable for the oil industry.

BACKGROUND: Improving the quality and shelf life of groundnut oil is one of the foremost objectives of groundnut breeding programmes. This can be achieved by marker-assisted introgression, a technique that efficiently and precisely enables breeders to develop plants with enhanced qualities. This study focused on improving the oleic acid content of an elite groundnut variety, TMV 7, by introgressing a recessive mutation responsible for the increase in oleic acid from ICG 15419. Hybridization was performed between the donor and recurrent parents to develop the F1, BC1F1, BC2F1 and BC2F2 populations. Introgressed lines with increased oleic acid in the genetic background of TMV 7 were identified using allele-specific marker, F435-F, F435SUB-R and a set of SSR markers were employed to recover the genome of the recurrent parent. RESULTS: With two backcrosses, a total of ten homozygous plants in the BC2F2 population were identified with oleic acid content ranging from 54.23 to 57.72% causing an increase of 36% over the recurrent parent. Among the ten lines, the line IL-23 exhibited the highest level of recurrent parent genome recovery of 91.12%. CONCLUSIONS: The phenotypic evaluation of 10 homozygous introgressed lines indicated fewer differences for all other traits under study compared to the recurrent parent, except for oleic acid and linoleic acid content confirming the genetic background of the recurrent parent. The identified lines will be subjected to multilocation trials before their commercial release.

Extensive Thrombosis in Catastrophic Antiphospholipid Syndrome in a Newly Diagnosed Systemic Lupus Erythematosus: A Case Report.

In this case report, we present the development of catastrophic antiphospholipid syndrome (CAPS), a rare and potentially fatal consequence of systemic lupus erythematosus (SLE), in a 33-year-old Micronesian woman. CAPS is characterized by extensive arterial thrombosis and multiorgan failure. The patient first showed signs of neuropsychiatric symptoms, brain infarctions on imaging, and severe hypoxic respiratory failure brought into the hospital by diffuse alveolar hemorrhage (DAH) along with lupus nephritis (LN). Blood urea nitrogen (BUN) and creatinine (Cr) were progressively elevated to 102/4.1 mg/dL, respectively. A urinalysis revealed microscopic hematuria and proteinuria with a urine protein/creatinine ratio of 6052 mg/g. She was also found to have had microangiopathic hemolytic anemia (MAHA) and severe venous thrombosis, both of which were indicative of CAPS. An aggressive approach, including immunosuppressive medication, therapeutic plasma exchange, and anticoagulation, had positive results, including renal recovery and the cessation of thrombotic episodes. This instance highlights how crucial it is to identify CAPS patients early and take appropriate action to improve patient outcomes for this difficult and sometimes deadly disorder.

Analysis of CYP1B1 Polymorphisms in Lung Cancer Patients Using Novel, Quick and Easy Methods Based on CAPS and ACRS-PCR Techniques.

Within the sequence of the CYP1B1 gene, more than 50 polymorphisms, resulting from single-nucleotide polymorphisms (SNPs), have been described. Some of them play an important role as specific genetic markers in the process of carcinogenesis and for therapeutic purposes. In this publication, we present methods we have developed that enable the specific and unambiguous identification of four polymorphisms that result in amino acid changes: c. 142C > G, c. 355G > T, c. 1294C > G, and c. 1358A > G. Our studies are based on cleaved amplified polymorphic sequences (CAPSs) and artificially created restriction site (ACRS) PCR techniques; therefore, they require only basic laboratory equipment and low financial outlays. Utilizing the described methods allows for the reduction of research time and cost, and the minimization of errors. Their effectiveness and efficiency depend on the careful design of appropriate primers and the precise selection of suitable restriction enzymes. As a result, further confirmation by sequencing is not necessary. Using the developed method, we examined 63 patients diagnosed with lung cancer and observed a 1.5 to 2.1 times higher frequency of the analyzed single-nucleotide polymorphisms compared to the frequency in the European population.

Catastrophic antiphospholipid syndrome after pregnancy complicated by hemolysis, elevated liver enzymes and low platelets syndrome.

Background: Antiphospholipid syndrome (APLS) is rarely complicated by catastrophic antiphospholipid syndrome (CAPS). Peripartum CAPS is rarer still and can masquerade as other obstetric disorders. A high degree of suspicion is critical for early diagnosis and specific management given the significant morbidity and mortality associated with this disorder. Case: We report a case of a 27-year-old at 22 week's gestation with a history of APLS found to have severe hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, resulting in termination of pregnancy. Further workup revealed the diagnosis of CAPS followed by prompt treatment with triple therapy leading to clinical improvement. Conclusion: CAPS should be considered within the differential in an obstetric patient with a history of APLS who has evidence of multiorgan involvement with macro- or microvascular thrombosis. Although this may mimic alternative disorders, prompt diagnosis is imperative for appropriate therapy and reduction in maternal morbidity and mortality.

The role of cap-assisted endoscopy and its future implications.

Cap-assisted endoscopy refers to a procedure in which a short tube made of a polymer (mostly transparent) is attached to the distal tip of the endoscope to enhance its diagnostic and therapeutic capabilities. It is reported to be particularly useful in: (1) minimizing blind spots during screening colonoscopy, (2) providing a constant distance from a lesion for clear visualization during magnifying endoscopy, (3) accurately assessing the size of various gastrointestinal lesions, (4) preventing mucosal injury during foreign body removal, (5) securing adequate workspace in the submucosal space during endoscopic submucosal dissection or third space endoscopy, (6) providing an optimal approach angle to a target, and (7) suctioning mucosal and submucosal tissue with negative pressure for resection or approximation. Here, we review various applications of attachable caps in diagnostic and therapeutic endoscopy and their future implications.

Triumph Over Adversity: A Comprehensive Case Series on Successful Pregnancy Outcomes in Antiphospholipid Antibody (APLA)-Positive Patients.

The intricate relationship between antiphospholipid antibody (APLA) syndrome and pregnancy outcomes challenges the prevailing notion of inevitable reproductive complications associated with APLA. The introduction provides a comprehensive overview of APLA, its autoimmune thrombophilic nature, and its common association with adverse pregnancy outcomes, emphasizing the need for a nuanced understanding. Here we discuss five case reports to showcase diverse scenarios, each highlighting successful pregnancies in APLA-positive patients, thereby contributing valuable insights into the management of this complex condition. The cases span various clinical presentations, patient demographics, and therapeutic approaches, emphasizing the heterogeneity of APLA-positive pregnancies and the importance of personalized care. The discussion delves into the broader context of APLA's impact on pregnancy, emphasizing recurrent miscarriage and venous thromboembolism (VTE) as severe complications. It underscores the significance of pre-conceptional counseling, a multidisciplinary approach, and regular antenatal monitoring in managing APLA-positive pregnancies. The identification of commonalities among the cases provides a basis for recognizing mitigating factors that contribute to positive outcomes, offering valuable guidance for healthcare providers. The series acknowledges the existence of catastrophic antiphospholipid syndrome (CAPS) and underscores the importance of early recognition and intervention in high-risk cases. Despite the challenges posed by APLA, the cases in the series offer a ray of hope by showcasing instances of successful pregnancies, attributing positive outcomes to optimized therapeutic interventions and vigilant antenatal care. In conclusion, the case series serves as a valuable resource for healthcare professionals, researchers, and policymakers, providing a nuanced perspective on APLA-positive pregnancies. By synthesizing diverse experiences and outcomes, the series contributes to the ongoing dialogue surrounding optimal management strategies, ultimately aiming to improve the quality of care for individuals facing the unique challenges posed by APLA during their reproductive journey.

[Cryopyrin-associated periodic fever syndrome (CAPS) presenting as early-onset dementia, lacking typical recurrent fever or skin rash: a case report].

A 54-year-old man with a university degree was admitted to our hospital because of a two-year history of progressive dementia. He had familial sensorineural hearing loss and had been treated for epilepsy since his 30s. On admission, he showed severe dementia and parkinsonism without fever or skin rash. Systemic inflammation was evident, and the CSF cell count and IL-6 level were elevated to 53/µl and 307 |pg/ml, respectively. Brain MRI demonstrated diffuse brain atrophy. More detailed anamnesis revealed a history of rheumatoid arthritis in childhood and aseptic meningitis in his 20s. Genetic examination for autoinflammatory diseases demonstrated compound heterozygotic mutations in the NLRP3 gene, causing cryopyrin-associated periodic fever syndrome (CAPS). This case was atypical CAPS presenting as early-onset progressive dementia, without recurrent fever or urticaria-like eruption which are usually seen in this disease.

A rare case of uncharacterized autoinflammatory disease: Patient carrying variations in NLRP3 and TNFRSF1A genes.

Tumor necrosis factor type 1A receptor-associated periodic syndrome (TRAPS) and cryopyrin-associated autoinflammatory syndrome (CAPS) are rare monogenic autoinflammatory diseases (AIDs) mainly caused by pathogenic variations in the TNFRSF1A and NLRP3 genes, respectively. Here, we describe a unique patient presenting with symptoms overlapping both TRAPS and CAPS, without known pathogenic variants in the respective genes. The patient harbored the p.Val200Met variation in NLRP3 and the p.Ser226Cys variation in TNFRSF1A, prompting us to delve deeper into the functional analysis due to conflicting or inconclusive pathogenicity interpretations of the variants across various databases. Molecular dynamics analysis of the p.Val200Met variation in NLRP3 revealed a rigid conformation in the helical domain 2 subdomain of the NACHT domain. This increased rigidity suggests a potential mechanism by which this variation supports the assembly of the NLRP3 inflammasome. Notably, the patient's peripheral mononuclear blood cells demonstrated an elevated IL-1ß response upon lipopolysaccharides (LPS) induction. Subsequent initiation of anti-IL-1ß therapy resulted in a significant alleviation of the patient's symptoms, further supporting our hypothesis. We interpret these findings as suggestive of a potential pathophysiological role for the NLPR3 p.Val200Met variation in shaping the patient's clinical phenotype, which was also supported by clinical and genetic analysis of the family. This case underscores the complexity of the genetic landscape in AIDs and highlights the value of combining family genetic and functional data to refine the understanding and management of such challenging cases.

Case Report: Efficacy, safety, and favorable long-term outcome of early treatment with IL-1 inhibitors in a patient with chronic infantile neurological cutaneous articular (CINCA) syndrome caused by NLRP3 mosaicism.

Chronic infantile neurological cutaneous articular (CINCA) syndrome is an autoinflammatory disease encompassed in the group of cryopyrin-associated periodic syndromes (CAPS). Patients suffering from CINCA have an elevated risk of developing chronic sequelae, including deforming arthropathy, chronic meningitis, neurodevelopmental delay, and neurosensorial hearing loss. The diagnosis of CINCA presents several difficulties, as the clinical phenotype could be difficult to recognize, and almost half of the patients have negative genetic testing. In this paper, we describe the case of a patient presenting with the typical phenotype of neonatal-onset CINCA who resulted negative for NLRP3 mutations. Based on the clinical judgment, the patient underwent treatment with anti-interleukin-1 (IL-1) agents (anakinra and, later, canakinumab) resulting in a complete clinical and laboratory response that allowed confirmation of the diagnosis. Additional genetic investigations performed after the introduction of anti-IL-1 therapy revealed a pathogenic mosaicism in the NLRP3 gene. After a 12-year follow-up, the patient has not experienced chronic complications. Although genetics is rapidly progressing, this case highlights the importance of early diagnosis of CINCA patients when the clinical and laboratory picture is highly suggestive in order to start the appropriate anti-cytokine treatment even in the absence of a genetic confirmation.

Meeting the Consultation Surge: A Nationwide Survey of Consult Volume and Mitigation Strategies in Infectious Diseases Fellowship Programs.

High patient volume in fellowship programs can affect learning, wellness, and patient outcomes. Training programs must find ways to mitigate high consultation volume to protect the learning environment. This survey describes average new consults and average censuses for infectious diseases training programs and strategies implemented to mitigate high volume.

Optimized Treatment of Interleukin (IL-1)-Mediated Autoinflammatory Diseases: Impact of Disease Activity-Based Treatment Adjustments.

Background: Effective control of disease activity in Interleukin-1 autoinflammatory diseases (IL-1 AID) is crucial to prevent damage. The aim was to longitudinally analyze the impact of protocolized disease activity-based treatment adjustments in a real-life cohort. Methods: A single-center study of consecutive children with IL-1 AID followed between January 2016 and December 2019 was performed. Demographics, phenotypes, genotypes, inflammatory markers, physician (PGA), and patient/parent (PPGA) global assessment were captured. Disease activity and treatment changes were assessed. The impact of distinct parameters on disease activity trajectories was analyzed. Results: A total of 56 children were included, median follow-up was 2.1 years reflecting 361 visits. Familial Mediterranean Fever was the most common IL-1 AID. At the first visit, 68% of the patients had moderate/severe disease activity. Disease activity-based treatment adjustments were required in 28/56 children (50%). At last follow-up, 79% had a well-controlled disease. Both PGA and PPGA decreased significantly over time (p < 0.001; p < 0.017, respectively), however, both differed statistically at last visit (p < 0.001). Only PGA showed a significant estimated mean decrease across all IL-1 AID over time. Conclusions: Disease activity-based treatment adjustments can effectively refine treat-to-target strategies, enable personalized precision health approaches, and improve outcomes in children with IL-1 AID.

Early altered directionality of resting brain network state transitions in the TgF344-AD rat model of Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disease resulting in memory loss and cognitive decline. Synaptic dysfunction is an early hallmark of the disease whose effects on whole-brain functional architecture can be identified using resting-state functional MRI (rsfMRI). Insights into mechanisms of early, whole-brain network alterations can help our understanding of the functional impact of AD's pathophysiology. Methods: Here, we obtained rsfMRI data in the TgF344-AD rat model at the pre- and early-plaque stages. This model recapitulates the major pathological and behavioral hallmarks of AD. We used co-activation pattern (CAP) analysis to investigate if and how the dynamic organization of intrinsic brain functional networks states, undetectable by earlier methods, is altered at these early stages. Results: We identified and characterized six intrinsic brain states as CAPs, their spatial and temporal features, and the transitions between the different states. At the pre-plaque stage, the TgF344-AD rats showed reduced co-activation of hub regions in the CAPs corresponding to the default mode-like and lateral cortical network. Default mode-like network activity segregated into two distinct brain states, with one state characterized by high co-activation of the basal forebrain. This basal forebrain co-activation was reduced in TgF344-AD animals mainly at the pre-plaque stage. Brain state transition probabilities were altered at the pre-plaque stage between states involving the default mode-like network, lateral cortical network, and basal forebrain regions. Additionally, while the directionality preference in the network-state transitions observed in the wild-type animals at the pre-plaque stage had diminished at the early-plaque stage, TgF344-AD animals continued to show directionality preference at both stages. Discussion: Our study enhances the understanding of intrinsic brain state dynamics and how they are impacted at the early stages of AD, providing a nuanced characterization of the early, functional impact of the disease's neurodegenerative process.

Measuring Paranoid Beliefs in Adolescents: A Comparison of the Revised-Green et al.'s Paranoid Thoughts Scale (R-GPTS) and the Bird Checklist of Adolescent Paranoia (B-CAP).

Research on paranoid beliefs in adolescents is in its infancy. Valid and reliable assessments are essential to advancing the field, yet there is no current consensus as to which are optimal to use in this population. This study compared the psychometric properties of two measures of paranoia in a general population adolescent sample. A cross-sectional study with quota sampling (gender and age) recruited adolescents (14-17 years) from the UK (n = 262) and USA (n = 200), who completed the Revised Green et al. Paranoid Thoughts Scale (R-GPTS) and the Bird Checklist for Adolescent Paranoia (B-CAP). We assessed factor structures, intercorrelations, overlap of participants identified as at-risk for paranoid thoughts via both scales, convergent validity (scales with one another) and discriminant validity (distress, wellbeing, bullying and discrimination). Both scales performed equally well in terms of factorial validity. Intercorrelations between the subscales and with general distress were high for both measures. However, a substantial percentage of participants were identified as having paranoid beliefs according to the R-GPTS but not the B-CAP. Furthermore, the B-CAP showed a very high correlations (0.69 ≤ r ≤ 0.79) with self-reported bullying experiences, which bordered on multicollinearity. Findings highlight the possibility that B-CAP may risk confounding paranoid beliefs with exposure to bullying more so than R-GPTS, and that B-CAP may miss instances of elevated paranoia that are captured by the R-GPTS. Future research needs to further explore this by validating both scales with an external (e.g., interview-based) criterion for paranoia.

Retrospective evaluation of Penguin Cold Caps for chemotherapy-induced alopecia.

BACKGROUND: Scalp cooling is an increasingly recognized non-pharmacologic approach to minimize chemotherapy-induced alopecia (CIA). Several commercially available machine-based and manual scalp cooling systems are available; however, literature reports of effectiveness are highly variable. The purpose of this study was to determine real-world tolerability and subjective effectiveness of a manual cold capping system in minimizing CIA across a variety of patient race and hair types. This study was a single-institution review of outcomes from manual cold capping. METHODS: We identified retrospective cohort of adult patients who presented to discuss cold capping between January 14, 2019, and March 31, 2022. Data collected from medical records included demographics, decision to pursue/continue cold capping, diagnoses, chemotherapy regimens, hair characteristics (length, thickness, coarseness, type), and subjective perception of percentage of hair retained. Those with successful vs. unsuccessful cold capping (≥ 50% vs. < 50% of hair retained) were compared based on the patient-level factors of interest. FINDINGS: A total of 100 patients initiated cold capping during the study period, and 95% of them completed cold capping. The majority of patients who started cold capping completed it. The median-reported percentage of hair maintained was 75%, and 82/89 (92.1% of patients) had favorable results, defined as ≥ 50% of hair retained. The only patient-level factor associated with favorable response was chemotherapy regimen, with fewer patients receiving doxorubicin-containing regimens having successful hair retention compared to other chemotherapy types (71.4% successful results vs. 95.7% for those receiving paclitaxel-containing regimens and 96.6% for those receiving docetaxel-containing regimens (p = 0.018). There was no difference in success based on patient race/ethnicity or hair characteristics. INTERPRETATION: The overall effectiveness (92.1%) in this study is consistent to higher than many literature reports. One possible reason for the high success in our cohort is compliance with cold capping protocols, meaning applying the cap in the appropriate manner and wearing the cap for the prescribed durations, which may impact effectiveness.

Analysis of dose-TSH response effect of levothyroxine soft-gel formulation.

Background: Hypothyroidism is treated with daily levothyroxine (LT4). In recent years, soft gel caps of LT4 (LT4-C) have been commercialized, and their performance has been optimized. Since guidelines recommend dose LT4 according to the tablet preparation efficacy, the present study was undertaken to obtain data about the daily requirement, normalized per body weight, of LT4-C. Methods: Patients undergoing LT4-C after total thyroidectomy and radioiodine treatment for differentiated thyroid carcinoma were selected. There was no specific indication of suppression of TSH (i.e., <0.5 or <0.1 mIU/L). Patients were required to maintain a stable LT4 dose during the study period. Patients with interfering factors were excluded from this study. Results: Thirty patients were enrolled (18 females and 12 males; median age, 50 years; median body weight, 71 kg; median LT4-C dose, 1.71 µg/kg/day). The analysis of patient age did not reveal any differences. The LT4-C dose correlated with free-T4 p = 0.03), but not with TSH (p = 0.42) and free-T3 (p = 0.13). TSH was <1.0 mIU/L in 90% of the cases. The LT4-C dose-TSH response effect was analysed by probit regression model: the probability to achieve TSH <1.0 mIU/l was 99% with a dose of 1.84 (95%CI 1.57-2.12) µg/kg/day, 75% with a dose of 1.38 µg/kg/day (95%CI 1.17-1.59), and 50% with a dose of 1.20 (95%CI 0.96-1.43). At ROC curve analysis, the most accurate cut-off of LT4-C dose to achieve TSH <1.0 mIU/l was 1.53 ug/kg/day with 70% sensitivity and 100% specificity. Conclusions: Athyreotic patients can be initially treated with an LT4-C dose lower than previously stated. Therefore, further prospective studies are warranted.

Tracing beach litter sources: Drink lids tell a different story from their bottles.

Water and soft drink bottles made from polyethylene terephthalate (PET) sink at sea unless they contain trapped air, whereas their lids are made from polymers that float and can drift long distances. We sampled loose lids and bottles at 21 South African beaches to compare their origins. The proportions of foreign-made bottles and lids were correlated, and increased away from urban centres, indicating that much land-based litter strands close to source areas. Over 80 % of foreign-made drink bottles and 90 % of lids came from Asia, but most bottles were manufactured in China, Malaysia-Singapore and the UAE, and were dumped from ships. By comparison, most loose lids were in poor condition after being carried across the Indian Ocean from Indonesia by the South Equatorial Current. Reducing PET drink bottles at sea requires enforcement of regulations banning dumping at sea, whereas reducing their lids requires better control of littering in source countries.

Nursing Students' Experience of a Poverty Simulation and Its Impact on Empathy and Social Justice Awareness: A Descriptive Qualitative Study.

Holistic nursing practice requires an understanding of the constraints of poverty as one of the social determinants of health. Future nurses need to be change agents for social justice. A descriptive, qualitative study was conducted to explore students' experience of the Missouri Association for Community Action Poverty Simulation© (CAPS) and its impact on empathy and social justice awareness among a purposive sample of 56 sophomore baccalaureate nursing students at a public university in the Northeastern United States. Inductive thematic analysis was applied to data collected from a postparticipation reflection paper. Five themes emerged: (a) emotions, (b) personal history of poverty, (c) empathy, (d) rising advocacy, and (e) lessons learned. The results support that the CAPS simulation provides an experiential opportunity which impacts empathy and foundational attitudes to be a change agent for social justice. Recommendations include structured education about social determinants of health prior to the CAPS simulation, continued education throughout nursing curricula, and experiential opportunities to apply social justice skills before graduation.

Quantum biochemical analysis of the binding interactions between a potential inhibitory drug and the Ebola viral glycoprotein.

Ebola virus disease (EVD) causes outbreaks and epidemics in West Africa that persist until today. The envelope glycoprotein of Ebola virus (GP) consists of two subunits, GP1 and GP2, and plays a key role in anchoring or fusing the virus to the host cell in its active form on the virion surface. Toremifene (TOR) is a ligand that mainly acts as an estrogen receptor antagonist; however, a recent study showed a strong and efficient interaction with GP. In this context, we aimed to evaluate the energetic affinity features involved in the interaction between GP and toremifene by computer simulation techniques using the Molecular Fractionation Method with Conjugate Caps (MFCC) scheme and quantum-mechanical (QM) calculations, as well as missense mutations to assess protein stability. We identified ASP522, GLU100, TYR517, THR519, LEU186, LEU515 as the most attractive residues in the EBOV glycoprotein structure that form the binding pocket. We divided toremifene into three regions and evaluated that region i was more important than region iii and region ii for the formation of the TOR-GP1/GP2 complex, which might control the molecular remodeling process of TOR. The mutations that caused more destabilization were ARG134, LEU515, TYR517 and ARG559, while those that caused stabilization were GLU523 and ASP522. TYR517 is a critical residue for the binding of TOR, and is highly conserved among EBOV species. Our results may help to elucidate the mechanism of drug action on the GP protein of the Ebola virus and subsequently develop new pharmacological approaches against EVD.Communicated by Ramaswamy H. Sarma.