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1.
Biomedicines ; 9(10)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34680490

RESUMO

The COVID-19 pandemic has become a serious concern and has negatively impacted public health and the economy. It primarily targets the lungs, causing acute respiratory distress syndrome (ARDS); however, it may also lead to multiple organ failure (MOF) and enhanced mortality rates. Hence, there is an urgent need to develop potential effective therapeutic strategies for COVID-19 patients. Extracellular vesicles (EVs) are released from various types of cells that participate in intercellular communication to maintain physiological and pathological processes. EVs derived from various cellular origins have revealed suppressive effects on the cytokine storm during systemic hyper-inflammatory states of severe COVID-19, leading to enhanced alveolar fluid clearance, promoted epithelial and endothelial recovery, and cell proliferation. Being the smallest subclass of EVs, exosomes offer striking characteristics such as cell targeting, being nano-carriers for drug delivery, high biocompatibility, safety, and low-immunogenicity, thus rendering them a potential cell-free therapeutic candidate against the pathogeneses of various diseases. Due to these properties, numerous studies and clinical trials have been performed to assess their safety and therapeutic efficacy against COVID-19. Hence, in this review, we have comprehensively described current updates on progress and challenges for EVs as a potential therapeutic agent for the management of COVID-19.

2.
Pharmaceuticals (Basel) ; 14(10)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34681192

RESUMO

Modeling the binding pose of an antibody is a prerequisite to structure-based affinity maturation and design. Without knowing a reliable binding pose, the subsequent structural simulation is largely futile. In this study, we have developed a method of machine learning-guided re-ranking of antigen binding poses of nanobodies, the single-domain antibody which has drawn much interest recently in antibody drug development. We performed a large-scale self-docking experiment of nanobody-antigen complexes. By training a decision tree classifier through mapping a feature set consisting of energy, contact and interface property descriptors to a measure of their docking quality of the refined poses, significant improvement in the median ranking of native-like nanobody poses by was achieved eightfold compared with ClusPro and an established deep 3D CNN classifier of native protein-protein interaction. We further interpreted our model by identifying features that showed relatively important contributions to the prediction performance. This study demonstrated a useful method in improving our current ability in pose prediction of nanobodies.

3.
Asian J Neurosurg ; 16(3): 518-524, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660363

RESUMO

Background: Mesial temporal lobe epilepsy attributed to low-grade glioma is known for intractable seizures and choice of surgery range from lesionectomy (Lo) to lesionectomy with anteromesial temporal resection (L0 + AMTR) is still debatable. We intend to analyze the seizure outcome after lesionectomy alone or with AMTR. Subjects and Methods: Retrospective analyses of patients operated for medial low-grade temporal lobe tumors with seizures were included in the study. Preoperative records include video-electroencephalographic, magnetic resonance imaging (epilepsy protocol), and neuropsychological evaluation for language, memory, and dominance were assessed. Two groups (Lo [Group I] and Lo + AMTR [Group II]) were assessed after surgery by the international league against epilepsy (ILAE) seizure outcome scale. Results: A total of 39 patients underwent Lo (n = 20) and Lo + AMTR (n = 19) with a mean age of 26.92 ± 12.96 months, and mean duration of seizures was 36.87 46.76 months. A total of 23 patients had long-term intractable seizures for >1 year despite >2 drugs(Group I [n = 10], Group II [n = 13]); remaining 16 had frequent seizures of <1-year duration. In the postoperative period, on a mean follow-up of 49.72 ± 34.10 months, the ILAE outcome scale shown a significant difference (P = 0.05) in seizure outcome between two groups. Four (40%) patients out of 10 having refractory seizures in Group I and 8 (80%) from the Group II out of 10 patients could achieved ILAE Class 1 outcome after surgery. Histopathology analysis includes low-grade astrocytoma (n = 29) and in two patients there were associated CA1 neuronal loss in hippocampus, one patient had mesial temporal sclerosis from Group II attributed to its intractability in seizures. Conclusion: For the mesial temporal low-grade glioma presenting with seizures, the seizure outcome by lesionectomy with AMTR is superior than lesionectomy only.

5.
Neurol India ; 69(4): 829-832, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34507396

RESUMO

Background and Introduction: Unlocking of the frontotemporal dural fold (FTDF) and extradural removal of the anterior clinoid process (EACP) are challenging but mandatory skills for micro-neurosurgeons. Despite the presence of an extensive body of literature on this subject, the translation of this cadaveric and 3D simulation to a real patient turns out to be a very demanding and difficult task. Objective: This video is aimed to address the surgical nuances and major adjustments necessary in the unlocking of the FTDF and extradural ACP removal in an actual case for an early-career neurosurgeon. Surgical Technique: A 40-year lady presented with features of acromegaly with radiological evidence of significant component of the tumor in the right cavernous sinus along with sellar suprasellar component. To achieve a good hormonal control, a complete tumor excision was required, which was achieved with FTDF and EACP removal. The cavernous sinus was approached through the Parkinson's triangle. Results: The patient had uneventful recovery and good hormonal control at the 3-month follow-up. Conclusion: FTDF unlocking and EACP are elegant procedures and need to be learned by all neurosurgeons. This article will provide excellent teaching material for young neurosurgeons.


Assuntos
Seio Cavernoso , Base do Crânio , Cadáver , Humanos , Neurocirurgiões , Procedimentos Neurocirúrgicos , Osso Esfenoide
6.
J Family Med Prim Care ; 10(7): 2661-2667, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34568152

RESUMO

Introduction: After almost two months of reporting the first case of the novel coronavirus disease (COVID-19) in the country, the nationwide lockdown in India was initiated on 24th of March 2020, to curtail the spread of the SARS-CoV-2 infection in the country. While this lockdown had been in place for almost 3 months, the people of the nation have experienced changes in their routine lives in a wide range of activities, including personal behaviours. This study was conducted to identify the impacts that the lockdown had on the lifestyle and behavioural aspects of Indians during the lockdown. Methods: It was a cross sectional study, conducted by online survey. Data collection was done for the period of 3 months. Results: The study found that a huge number of participants had significant changes in their diet, sleep, bowel habits and also their personal traits. Also, the lockdown had improved interpersonal relationships and helped people explore their hobbies or even acquire a new skill (about 25% of the participants). More than 90% of the participants perceived decrease in air pollution and a majority reported increase in personal hygiene (74.2%), perceived decrease in crime rates (67.3%) as benefits of lockdown. Conclusions: It would be recommended to include variables to screen for mental health issues among the general population.

7.
Sci Rep ; 11(1): 18796, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34552136

RESUMO

The possibility of using quantum computers for electronic structure calculations has opened up a promising avenue for computational chemistry. Towards this direction, numerous algorithmic advances have been made in the last five years. The potential of quantum annealers, which are the prototypes of adiabatic quantum computers, is yet to be fully explored. In this work, we demonstrate the use of a D-Wave quantum annealer for the calculation of excited electronic states of molecular systems. These simulations play an important role in a number of areas, such as photovoltaics, semiconductor technology and nanoscience. The excited states are treated using two methods, time-dependent Hartree-Fock (TDHF) and time-dependent density-functional theory (TDDFT), both within a commonly used Tamm-Dancoff approximation (TDA). The resulting TDA eigenvalue equations are solved on a D-Wave quantum annealer using the Quantum Annealer Eigensolver (QAE), developed previously. The method is shown to reproduce a typical basis set convergence on the example [Formula: see text] molecule and is also applied to several other molecular species. Characteristic properties such as transition dipole moments and oscillator strengths are computed as well. Three potential energy profiles for excited states are computed for [Formula: see text] as a function of the molecular geometry. Similar to previous studies, the accuracy of the method is dependent on the accuracy of the intermediate meta-heuristic software called qbsolv.

8.
Pediatrics ; 148(3)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34385350

RESUMO

Neonatal herpes simplex virus encephalitis (HSVE) often results in long-lasting neuro-disability in affected children. In addition to primary HSVE and HSVE relapses, children with herpes simplex virus are at increased risk of developing anti-N-methyl-d-aspartate receptor encephalitis (NMDARe), an autoimmune encephalitis. In this study, we describe a patient with neonatal disseminated herpes infection, who developed HSVE after discontinuation of 2 years of acyclovir suppressive therapy. After resolution of HSVE, the patient rapidly deteriorated with significant behavioral and neurologic changes including emotional outbursts, fearfulness, involuntary movements, and focal seizures. The patient was diagnosed with anti-NMDARe and was later found to have low toll-like receptor-3 function. In this study, we review published pediatric cases of anti-NMDARe after HSVE as well as previous literature and primary data examining the presentation, predisposing risk factors, predictive outcomes, future directions, and the role of immunodeficiency in HSVE-mediated anti-NMDARe. The neonatal immune system and developing brain are disproportionately vulnerable to early viral exposure; therefore, it is important to recognize the value of early immunodeficiency screening in patients with neonatal herpes simplex virus. By understanding the immune landscape within this patient population, we can mitigate long-term neurologic disability and improve the quality of life of affected children.


Assuntos
Aciclovir/uso terapêutico , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Antivirais/uso terapêutico , Herpes Simples/tratamento farmacológico , Encefalite Antirreceptor de N-Metil-D-Aspartato/tratamento farmacológico , Encéfalo/diagnóstico por imagem , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Imageamento por Ressonância Magnética , Masculino , Gravidez , Complicações Infecciosas na Gravidez/virologia
9.
Biochemistry ; 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34431665

RESUMO

Liquid-liquid phase separation (LLPS) is a crucial phenomenon for the formation of functional membraneless organelles. However, LLPS is also responsible for protein aggregation in various neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease (PD). Recently, several reports, including ours, have shown that α-synuclein (α-Syn) undergoes LLPS and a subsequent liquid-to-solid phase transition, which leads to amyloid fibril formation. However, how the environmental (and experimental) parameters modulate the α-Syn LLPS remains elusive. Here, we show that in vitro α-Syn LLPS is strongly dependent on the presence of salts, which allows charge neutralization at both terminal segments of protein and therefore promotes hydrophobic interactions supportive for LLPS. Using various purification methods and experimental conditions, we showed, depending upon conditions, α-Syn undergoes either spontaneous (instantaneous) or delayed LLPS. Furthermore, we delineate that the kinetics of liquid droplet formation (i.e., the critical concentration and critical time) is relative and can be modulated by the salt/counterion concentration, pH, presence of surface, PD-associated multivalent cations, and N-terminal acetylation, which are all known to regulate α-Syn aggregation in vitro. Together, our observations suggest that α-Syn LLPS and subsequent liquid-to-solid phase transition could be pathological, which can be triggered only under disease-associated conditions (high critical concentration and/or conditions promoting α-Syn self-assembly). This study will significantly improve our understanding of the molecular mechanisms of α-Syn LLPS and the liquid-to-solid transition.

10.
Brief Bioinform ; 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34415295

RESUMO

Protein engineering and design principles employing the 20 standard amino acids have been extensively used to achieve stable protein scaffolds and deliver their specific activities. Although this confers some advantages, it often restricts the sequence, chemical space, and ultimately the functional diversity of proteins. Moreover, although site-specific incorporation of non-natural amino acids (nnAAs) has been proven to be a valuable strategy in protein engineering and therapeutics development, its utility in the affinity-maturation of nanobodies is not fully explored. Besides, current experimental methods do not routinely employ nnAAs due to their enormous library size and infinite combinations. To address this, we have developed an integrated computational pipeline employing structure-based protein design methodologies, molecular dynamics simulations and free energy calculations, for the binding affinity prediction of an nnAA-incorporated nanobody toward its target and selection of potent binders. We show that by incorporating halogenated tyrosines, the affinity of 9G8 nanobody can be improved toward epidermal growth factor receptor (EGFR), a crucial cancer target. Surface plasmon resonance (SPR) assays showed that the binding of several 3-chloro-l-tyrosine (3MY)-incorporated nanobodies were improved up to 6-fold into a picomolar range, and the computationally estimated binding affinities shared a Pearson's r of 0.87 with SPR results. The improved affinity was found to be due to enhanced van der Waals interactions of key 3MY-proximate nanobody residues with EGFR, and an overall increase in the nanobody's structural stability. In conclusion, we show that our method can facilitate screening large libraries and predict potent site-specific nnAA-incorporated nanobody binders against crucial disease-targets.

11.
Child Neurol Open ; 8: 2329048X211030751, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34377735

RESUMO

Infection-induced acute encephalopathy 3 (IIAE3) is an autosomal dominant disease resulting from a pathogenic variant in the RANBP2 gene. IIAE3 results in the susceptibility to the recurrence of acute necrotizing encephalopathy (ANE1) which presents as bilateral symmetric thalamic, midbrain and/or hindbrain lesions that typically develops within 1-4 days post-acute viral infection, commonly occurring before age 6.1-6 These case reports highlight a retrospective analysis of clinical data and radiographic studies on 2 ANE1 cases from our institution. The novel p.Leu450Phe variant of the RANBP2 gene was analyzed using in silico algorithms (PolyPhen-2, SIFT, Mutationtaster) which suggests the p.Leu450Phe variant is probably deleterious.7 An expansion of documented ANE1 case presentations and clinically significant RANBP2 gene mutations has the potential to improve long term outcomes if more informed therapeutic decision making can be achieved.

12.
Expert Rev Mol Med ; 23: e7, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34340720

RESUMO

Recent epidemiological studies analysing sex-disaggregated patient data of coronavirus disease 2019 (COVID-19) across the world revealed a distinct sex bias in the disease morbidity as well as the mortality - both being higher for the men. Similar antecedents have been known for the previous viral infections, including from coronaviruses, such as severe acute respiratory syndrome (SARS) and middle-east respiratory syndrome (MERS). A sound understanding of molecular mechanisms leading to the biological sex bias in the survival outcomes of the patients in relation to COVID-19 will act as an essential requisite for developing a sex-differentiated approach for therapeutic management of this disease. Recent studies which have explored molecular mechanism(s) behind sex-based differences in COVID-19 pathogenesis are scarce; however, existing evidence, for other respiratory viral infections, viz. SARS, MERS and influenza, provides important clues in this regard. In attempt to consolidate the available knowledge on this issue, we conducted a systematic review of the existing empirical knowledge and recent experimental studies following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The qualitative analysis of the collected data unravelled multiple molecular mechanisms, such as evolutionary and genetic/epigenetic factors, sex-linkage of viral host cell entry receptor and immune response genes, sex hormone and gut microbiome-mediated immune-modulation, as the possible key reasons for the sex-based differences in patient outcomes in COVID-19.


Assuntos
COVID-19/epidemiologia , Microbioma Gastrointestinal/imunologia , Imunidade/genética , Pandemias , SARS-CoV-2/imunologia , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/virologia , Epigênese Genética , Feminino , Humanos , Masculino , Receptores Virais/genética , Fatores Sexuais , Resultado do Tratamento
13.
Cells ; 10(8)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34440715

RESUMO

Amyloid precursor protein (APP), upon proteolytic degradation, forms aggregates of amyloid ß (Aß) and plaques in the brain, which are pathological hallmarks of Alzheimer's disease (AD). Cathepsin B is a cysteine protease enzyme that catalyzes the proteolytic degradation of APP in the brain. Thus, cathepsin B inhibition is a crucial therapeutic aspect for the discovery of new anti-Alzheimer's drugs. In this study, we have employed mixed-feature ligand-based virtual screening (LBVS) by integrating pharmacophore mapping, docking, and molecular dynamics to detect small, potent molecules that act as cathepsin B inhibitors. The LBVS model was generated by using hydrophobic (HY), hydrogen bond acceptor (HBA), and hydrogen bond donor (HBD) features, using a dataset of 24 known cathepsin B inhibitors of both natural and synthetic origins. A validated eight-feature pharmacophore hypothesis (Hypo III) was utilized to screen the Maybridge chemical database. The docking score, MM-PBSA, and MM-GBSA methodology was applied to prioritize the lead compounds as virtual screening hits. These compounds share a common amide scaffold, and showed important interactions with Gln23, Cys29, His110, His111, Glu122, His199, and Trp221. The identified inhibitors were further evaluated for cathepsin-B-inhibitory activity. Our study suggests that pyridine, acetamide, and benzohydrazide compounds could be used as a starting point for the development of novel therapeutics.

14.
Indian J Hematol Blood Transfus ; 37(3): 372-378, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34267454

RESUMO

Epstein Barr virus (EBV) associated Hodgkin lymphoma (HL) has been defined as cases with clonal EBV infection, EBV genome and gene products in the Reed Sternberg cells. We evaluated the prevalence and clinico-pathological association of EBV in North Indian HL patients. Eighty-eight cases of histologically confirmed classic HL were evaluated for EBV by both IHC expression of LMP1 and real time PCR on formalin fixed lymph node tissue. The expression pattern was analyzed for any association with clinical and histomorphological parameters. Nodular sclerosis subtype was seen in 79.5% patients and mixed cellularity was seen in the remaining patients. Ninety percent of the cases were positive for EBV. The detection rate of EBV by IHC was higher. The EBV positive cases presented with higher disease stage (p < 0.05). The presence of histomorphological features like granuloma formation (5/5), atypical lymphocytes (8/8), histiocyte clusters (26/28), large area of necrosis (11/12), less prominent inflammatory response (25/27) was associated with EBV positivity (p > 0.05). In our study population a high proportion of HL cases showed positivity for EBV indicating a pathogenic role. The positivity was independent of age, gender and histological subtype. Further evaluation of EBV positivity in modulation of tumor immunity may provide insights into variable treatment outcome in EBV positive cases.

15.
J Neurosci Rural Pract ; 12(3): 571-580, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34295114

RESUMO

Objectives Intraparenchymal epidermoid cysts (IECs) are rare lesions. They represent less than 1% of the intracranial epidermoid cysts. The supratentorial IEC is a clinically and prognostically distinct subset. Given the rarity, most of the articles are case reports. We present a series of five cases of supratentorial IEC to characterize their clinical presentation and outcome, with emphasis on the surgical features. Materials and Methods We searched our database for all cases of intracranial epidermoid cysts operated between January 2005 and January 2020. Five patients were identified having IEC from the hospital information system and the neurosurgical operation record book. Standard craniotomy and decompression of the lesion were performed in all these patients. Standard postoperative care includes computed tomography scan of head on the day of surgery and magnetic resonance imaging of brain after 6 weeks to look for the residual lesion, if any. Subsequent follow-up visits in outpatient department to look for resolution of the presurgical symptoms. Results The mean age of the patients in our series was 28.8 years (range: 28-40 years.). All the five patients were male. Four patients had IEC involving frontal lobe and one in parietal lobe with a small occipital lobe extension. Seizure was the most common presenting complaint followed by headache. Complete excision was achieved in all the cases. All the three patients with seizure attained seizure freedom postlesionectomy. Focal neurological deficits resolved gradually in postoperative period. There was no recurrence of lesion during follow-up. Conclusion Supratentorial IEC most commonly affects young males, involve frontal lobe and present clinically with seizure. Complete surgical excision offers best outcome in the form of remission of seizure disorder.

16.
Indian Pediatr ; 58(7): 686-687, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34315835

RESUMO

This retrospective study describes the clinical profile, risk of infection and outcome of coronavirus disease-19 in immuno-compromised children. It was found that children on immuno-suppressant medication has 2.89 times increased risk of infection (P=0.01). Disease manifestation was asymptomatic (P=0.01) or mild with predominant gastrointestinal symptoms (P=0.02) without alteration in immunosuppressive treatment regime.


Assuntos
COVID-19 , Criança , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Estudos Retrospectivos , SARS-CoV-2
17.
Drugs R D ; 21(3): 273-283, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34324175

RESUMO

BACKGROUND AND OBJECTIVE: Coronavirus disease 2019 is a novel disease caused by the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 virus. It was first detected in December 2019 and has since been declared a pandemic causing millions of deaths worldwide. Therefore, there is an urgent need to develop effective therapeutics against coronavirus disease 2019. A critical step in the crosstalk between the virus and the host cell is the binding of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein to the peptidase domain of the angiotensin-converting enzyme 2 (ACE2) receptor present on the surface of host cells. METHODS: An in silico approach was employed to design a 13-amino acid peptide inhibitor (13AApi) against the RBD of the SARS-CoV-2 spike protein. Its binding specificity for RBD was confirmed by molecular docking using pyDockWEB, ClusPro 2.0, and HDOCK web servers. The stability of 13AApi and the SARS-CoV-2 spike protein complex was determined by molecular dynamics simulation using the GROMACS program while the physicochemical and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of 13AApi were determined using the ExPASy tool and pkCSM server. Finally, in vitro validation of the inhibitory activity of 13AApi against the spike protein was performed by an enzyme-linked immunosorbent assay. RESULTS: In silico analyses indicated that the 13AApi could bind to the RBD of the SARS-CoV-2 spike protein at the ACE2 binding site with high affinity. In vitro experiments validated the in silico findings, showing that 13AApi could significantly block the RBD of the SARS-CoV-2 spike protein. CONCLUSIONS: Blockage of binding of the SARS-CoV-2 spike protein with ACE2 in the presence of the 13AApi may prevent virus entry into host cells. Therefore, the 13AApi can be utilized as a promising therapeutic agent to combat coronavirus disease 2019.


Assuntos
Enzima de Conversão de Angiotensina 2/efeitos dos fármacos , Antivirais/farmacologia , Peptídeos/farmacologia , Glicoproteína da Espícula de Coronavírus/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/metabolismo , Antivirais/farmacocinética , Antivirais/toxicidade , Sítios de Ligação , Simulação por Computador , Desenho de Fármacos , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Peptídeos/farmacocinética , Peptídeos/toxicidade , Ligação Proteica/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/metabolismo , Especificidade por Substrato
18.
Indian J Psychiatry ; 63(2): 200-201, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34194068
19.
Mol Neurobiol ; 58(9): 4575-4587, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34110602

RESUMO

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 or COVID-19 has been declared as a pandemic disease by the World Health Organization (WHO). Globally, this disease affected 159 million of the population and reported ~ 3.3 million deaths to the current date (May 2021). There is no definitive treatment strategy that has been identified, although this disease has prevailed in its current form for the past 18 months. The main challenges in the (SARS-CoV)-2 infections are in identifying the heterogeneity in viral strains and the plausible mechanisms of viral infection to human tissues. In parallel to the investigations into the patho-mechanism of SARS-CoV-2 infection, understanding the fundamental processes underlying the clinical manifestations of COVID-19 is very crucial for designing effective therapies. Since neurological symptoms are very apparent in COVID-19 infected patients, here, we tried to emphasize the involvement of redox imbalance and subsequent mitochondrial dysfunction in the progression of the COVID-19 infection. It has been articulated that mitochondrial dysfunction is very apparent and also interlinked to neurological symptoms in COVID-19 infection. Overall, this article provides an in-depth overview of redox imbalance and mitochondrial dysfunction involvement in aggravating COVID-19 infection and its probable contribution to the neurological manifestation of the disease.


Assuntos
COVID-19/complicações , Mitocôndrias/fisiologia , SARS-CoV-2/patogenicidade , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , COVID-19/metabolismo , Sistema Nervoso Central/virologia , Reposicionamento de Medicamentos , Endotélio Vascular/fisiopatologia , Endotélio Vascular/virologia , Humanos , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Modelos Biológicos , Nervo Olfatório/virologia , Especificidade de Órgãos , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Pandemias , SARS-CoV-2/fisiologia , Proteínas Virais/fisiologia , Tropismo Viral , Viremia/complicações , Virulência , Internalização do Vírus
20.
Mol Inform ; 40(8): e2100020, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34060234

RESUMO

Acetylcholinesterase (AChE) inhibitors are the most effective drugs for Alzheimer's disease treatment. However, considering the potential and failure rates of AChE inhibitors, chemical scaffolds targeting cholinesterase specifically are still very limited. Herein, we report a new class of AChE inhibitors identified by employing a virtual screening approach that combines shape similarity with molecular docking calculations. Virtual screening followed by the evaluation of AChE inhibitory activity allowed us to identify 1,2,4-triazolylthioethanones as a novel class of AChE inhibitors. Thirteen compounds with 1,2,4-triazolylthiothanone core and IC50 values in the range of 0.15±0.07 to 3.32±0.92 µM have been reported here. Our findings shed light into a class of AChE inhibitors that could be useful starting point for the development of novel therapeutics to tackle Alzheimer's disease.

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