scholarly journals Small Molecules—Prospective Novel HCMV Inhibitors

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 474
Author(s):  
Elke Bogner ◽  
Anna Egorova ◽  
Vadim Makarov
Keyword(s):  
Small Molecules ◽  
Hcmv Infection ◽  
Viral Proteins ◽  
Short Review ◽  
Organ Damage ◽  
Modes Of Action ◽  
Antiviral Compounds ◽  
Life Threatening ◽  
Host Cell Factors ◽  
Selection Of

Human cytomegalovirus (HCMV), a member of the betaherpesvirinae, can cause life-threatening diseases. HCMV is globally widespread, with a seroprevalence in adults varying from 50 to 100%. HCMV infection is rarely of significant consequence in immunocompetent individuals. However, although immune control is efficient, it cannot achieve the clearance of the virus. HCMV persists lifelong in the infected host and reactivates in certain circumstances. In neonates and in immunocompromised adults, HCMV is a serious pathogen that can cause fatal organ damage. Different antiviral compounds alone or in combination have been used for the treatment of HCMV diseases. In clinical use, mutations in the viral DNA polymerase or the terminase confer resistance to ganciclovir, foscarnet, cidofovir, and letermovir. There is an urgent need to find new well-tolerated compounds supporting different modes of action. The list of novel small molecules that might have anti-HCMV activity has grown in recent years. In this short review, a selection of compounds in clinical trials and novel inhibitors targeting host-cell factors or viral proteins is presented, and their modes of action, described.

scholarly journals Extraneous E-Cadherin Engages the Deterministic Process of Somatic Reprogramming through Modulating STAT3 and Erk1/2 Activity

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 284
Author(s):  
Yu-Hao Liu ◽  
Chien-Chang Chen ◽  
Yi-Jen Hsueh ◽  
Li-Man Hung ◽  
David Hui-Kang Ma ◽  
...  
Keyword(s):  
Stochastic Process ◽  
Molecular Mechanism ◽  
Activity Ratio ◽  
Cell Types ◽  
Deterministic Process ◽  
Modes Of Action ◽  
Molecular Events ◽  
Different Cell Types ◽  
Selection Of ◽  
E Cadherin

Although several modes of reprogramming have been reported in different cell types during iPSC induction, the molecular mechanism regarding the selection of different modes of action is still mostly unknown. The present study examined the molecular events that participate in the selection of such processes at the onset of somatic reprogramming. The activity of STAT3 versus that of Erk1/2 reversibly determines the reprogramming mode entered; a lower activity ratio favors the deterministic process and vice versa. Additionally, extraneous E-cadherin facilitates the early events of somatic reprogramming, potentially by stabilizing the LIF/gp130 and EGFR/ErbB2 complexes to promote entry into the deterministic process. Our current findings demonstrated that manipulating the pSTAT3/pErk1/2 activity ratio in the surrounding milieu can drive different modes of action toward either the deterministic or the stochastic process in the context of OSKM-mediated somatic reprogramming.

scholarly journals De Novo Drug Design Using Artificial Intelligence Applied on SARS-CoV-2 Viral Proteins ASYNT-GAN

BioChem ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 36-48
Author(s):  
Ivan Jacobs ◽  
Manolis Maragoudakis
Keyword(s):  
Deep Learning ◽  
Small Molecules ◽  
Natural Product ◽  
De Novo ◽  
Viral Proteins ◽  
Computer Assisted ◽  
De Novo Drug Design ◽  
Learning Techniques ◽  
Latent Space ◽  
Synthetic Molecule

Computer-assisted de novo design of natural product mimetics offers a viable strategy to reduce synthetic efforts and obtain natural-product-inspired bioactive small molecules, but suffers from several limitations. Deep learning techniques can help address these shortcomings. We propose the generation of synthetic molecule structures that optimizes the binding affinity to a target. To achieve this, we leverage important advancements in deep learning. Our approach generalizes to systems beyond the source system and achieves the generation of complete structures that optimize the binding to a target unseen during training. Translating the input sub-systems into the latent space permits the ability to search for similar structures, and the sampling from the latent space for generation.

scholarly journals On a Magical Mystery Tour of Green Insecticide Research: Current Issues and Challenges

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5014
Author(s):  
Giovanni Benelli
Keyword(s):  
Cutting Edge ◽  
Plant Origin ◽  
Behavioral Traits ◽  
Modes Of Action ◽  
Natural Substances ◽  
The Impact ◽  
Lethal Doses ◽  
Selection Of

The Editorial outlines recent research advances in green insecticide research. Particular attention is devoted to studies shedding light on the modes of action and non-target toxicity of natural substances of plant origin. Research focusing on the development of new formulations (including those relating to nano-objects) to magnify the effectiveness and stability of green insecticides in the field represents key advances. Herein, a carefully reviewed selection of cutting edge articles about green pesticide development recently published in Molecules is presented. The impact of sub-lethal doses of green insecticides on insect behavioral traits is still overlooked, representing a timely challenge for further research.

scholarly journals Viral Infections and Autoimmune Disease: Roles of LCMV in Delineating Mechanisms of Immune Tolerance

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 885
Author(s):  
Georgia Fousteri ◽  
Amy Dave Jhatakia
Keyword(s):  
Immune System ◽  
Autoimmune Disease ◽  
Viral Infections ◽  
Molecular Mimicry ◽  
Short Review ◽  
Organ Damage ◽  
Lymphocytic Choriomeningitis ◽  
Immune Deviation ◽  
Viral Pathogen ◽  
Lcmv Infection

Viral infections are a natural part of our existence. They can affect us in many ways that are the result of the interaction between the viral pathogen and our immune system. Most times, the resulting immune response is beneficial for the host. The pathogen is cleared, thus protecting our vital organs with no other consequences. Conversely, the reaction of our immune system against the pathogen can cause organ damage (immunopathology) or lead to autoimmune disease. To date, there are several mechanisms for virus-induced autoimmune disease, including molecular mimicry and bystander activation, in support of the “fertile field” hypothesis (terms defined in our review). In contrast, viral infections have been associated with protection from autoimmunity through mechanisms that include Treg invigoration and immune deviation, in support of the “hygiene hypothesis”, also defined here. Infection with lymphocytic choriomeningitis virus (LCMV) is one of the prototypes showing that the interaction of our immune system with viruses can either accelerate or prevent autoimmunity. Studies using mouse models of LCMV have helped conceive and establish several concepts that we now know and use to explain how viruses can lead to autoimmune activation or induce tolerance. Some of the most important mechanisms established during the course of LCMV infection are described in this short review.

Exact analysis of the bending of wide beams by a modified elastica approach

2011 ◽  
Vol 225 (11) ◽  
pp. 2759-2764 ◽  
Author(s):  
L F Campanile ◽  
R Jähne ◽  
A Hasse
Keyword(s):  
Finite Element ◽  
Substantial Reduction ◽  
Short Review ◽  
Computational Effort ◽  
Two Dimensional ◽  
Finite Element Calculations ◽  
Dimensional Finite Element ◽  
Wide Beams ◽  
Insight Into ◽  
Selection Of

Classical beam models do not account for partial restraint of anticlastic bending and are therefore inherently inaccurate. This article proposes a modification of the exact Bernoulli–Euler equation which allows for an exact prediction of the beam's deflection without the need of two-dimensional finite element calculations. This approach offers a substantial reduction in the computational effort, especially when coupled with a fast-solving schema like the circle-arc method. Besides the description of the new method and its validation, this article offers an insight into the somewhat disregarded topic of anticlastic bending by a short review of the published theories and a selection of representative numerical results.

Cancer and COVID-19: A proposed mechanism with therapeutic interventions.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3135-3135
Author(s):  
Yan Leyfman ◽  
Nancy Emmanuel ◽  
Aleksey Tentler ◽  
Jared Cappelli ◽  
Timothy K Erick ◽  
...  
Keyword(s):  
Respiratory Illness ◽  
Organ Damage ◽  
Multiple Organ ◽  
Therapeutic Interventions ◽  
Actual Number ◽  
Data Registry ◽  
Number Of Patients ◽  
Increased Risk ◽  
Life Threatening ◽  
Active Cancer

3135 Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel betacoronavirus that causes the respiratory illness coronavirus disease 2019 (COVID-19). COVID-19 ranges in severity from an asymptomatic viral infection to life-threatening cases of pneumonia, acute respiratory distress syndrome (ARDS), multi-organ damage and sepsis. Cancer patients are at an increased risk of severe SARS-CoV-2 infection due to their immunocompromised status. We propose a mechanism by which SARS-CoV-2 infection causes multiple organ damage through IL-6-mediated inflammation and hypoxia-induced cellular metabolic alterations leading to cell death. Hypoxia is also induced by malignancy due to alterations in metabolism, resulting in greater IL-6 secretion. Methods: To highlight the possible effect of active cancer on the likelihood of hypoxia in COVID-19, we analyzed the correlation between cancer status and the severity of COVID-19 from the COVID-19 and Cancer Consortium data registry. For cancer status, we looked at progressive cancer and remission of cancer only -- those being the two extremes of presence and absence of uncontrolled cancer. Similar to prior studies, the severity of COVID-19 was used as an indication of hypoxia. Results: We observed a 24% positive deviation between expected and actual number of patients with actively progressing cancer who had hypoxic COVID-19 (moderate to severe), and a 26.9% negative deviation between expected and actual number of patients with active cancer who had no hypoxia with COVID-19 (p<0.0001). Conversely, for patients with cancer in remission, there was only a +5.8% and -5.1% deviation between expected and actual number of patients who did not have hypoxia and who had hypoxia, respectively. Conclusions: These results suggest that in the presence of poorly controlled malignancy, there is an increased likelihood of hypoxia in patients with COVID-19, thereby exacerbating downstream cytokine release syndrome and contributing to prolonged systemic inflammatory injury. Appreciating this pathway, future therapies can be developed to target the pathogenesis of both diseases and prevent progression, as seen with mesenchymal stem cells, which demonstrated a 91% overall survival and 100% survival in patients younger than 85 years old at one month after a single treatment.[Table: see text]

scholarly journals Survival from paraquat induced renal impairment in a 17 years old male

2021 ◽  
Vol 8 (2) ◽  
pp. 300
Author(s):  
Medo M. Kuotsu ◽  
N. Biplab Singh ◽  
Nyamnyei Konyak ◽  
Vikie-o Khruomo ◽  
Senjele Kath ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Treatment Options ◽  
Fatal Outcome ◽  
Radical Scavenging ◽  
Case Fatality ◽  
Kidney Injury ◽  
Organ Damage ◽  
Paraquat Poisoning ◽  
Adequate Hydration ◽  
Life Threatening

N, N’-dimethyl-4, 4’-bipyridinium dichloride (paraquat) is a herbicide commonly used in India that leads to fatal outcome on ingestion. Paraquat interferes in the intracellular electron transfer systems inhibiting the reduction of NADP to NADPH resulting in accumulation of superoxide radical causing lipid cell membranes destruction leading to various organ damage. Life threatening effects such as acute kidney injury as paraquat elimination is mainly by kidney, acute respiratory distress syndrome and multi-organ failure are the causes of mortality in paraquat poisoning. There is no specific antidotes for paraquat poisoning so prevention and aggressive decontamination remains the mainstay of management in case of exposure or ingestion. Paraquat poisoning presentation may vary in cases depending on the amount of paraquat consumed and thus the outcome. Here we report a case of a 17 years old male who presented with acute kidney injury following ingestion of paraquat in a suicidal attempt. In our case, induced vomiting of the stomach content readily after ingestion of the poison, early haemodialysis, use of immunosuppression such as methylprednisolone, cyclophosphamide and antioxidants such as acetylcysteine, Vitamin C and Vitamin E as free radical scavenging agent , supportive measures such as adequate hydration and antibiotics might have helped in the patient’s survival. The case fatality remains very high in paraquat poisoning till date owing to lack of effective treatment options.

scholarly journals Anderson–Fabry Disease: From Endothelial Dysfunction to Emerging Therapies

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Cosimo A. Stamerra ◽  
Rita Del Pinto ◽  
Paolo di Giosia ◽  
Claudio Ferri ◽  
Amirhossein Sahebkar
Keyword(s):  
Fabry Disease ◽  
Organ Damage ◽  
Lysosomal Storage ◽  
Messenger Ribonucleic Acid ◽  
Gene Therapies ◽  
Enzyme Replacement ◽  
Emerging Therapies ◽  
Life Threatening ◽  
Molecular Aspects ◽  
Partial Deficiency

The Anderson–Fabry disease is a rare, X-linked, multisystemic, progressive lysosomal storage disease caused by α-galactosidase A total or partial deficiency. The resulting syndrome is mainly characterized by early-onset autonomic neuropathy and life-threatening multiorgan involvement, including renal insufficiency, heart disease, and early stroke. The enzyme deficiency leads to tissue accumulation of the glycosphingolipid globotriaosylceramide and its analogues, but the mechanisms linking such accumulation to organ damage are only partially understood. In contrast, enzyme replacement and chaperone therapies are already fully available to patients and allow substantial amelioration of quality and quantity of life. Substrate reduction, messenger ribonucleic acid (mRNA)-based, and gene therapies are also on the horizon. In this review, the clinical scenario and molecular aspects of Anderson–Fabry disease are described, along with updates on disease mechanisms and emerging therapies.

scholarly journals Void and Moisture Content of Fiber Reinforced Composites

2021 ◽  
Vol 87 (3) ◽  
pp. 78-93
Author(s):  
Nurul Zuhairah Mahmud Zuhudi ◽  
Afiq Faizul Zulkifli ◽  
Muzafar Zulkifli ◽  
Ahmad Naim Ahmad Yahaya ◽  
Nurhayati Mohd Nur ◽  
...  
Keyword(s):  
Moisture Content ◽  
Short Review ◽  
Fiber Reinforced Composites ◽  
Moisture Determination ◽  
Reinforced Composites ◽  
Fiber Reinforced ◽  
Mechanical Performances ◽  
Future Work ◽  
Selection Of

In this paper, a short review on the void and moisture content studies of fiber reinforced composites for both, synthetic and natural based fibers are presented. The review summarized the research papers in which include experimental and theoretical works that related to the void and moisture content studies. In addition to that, this review paper highlighting a few research studies conducted in literature on the effects of the void and moisture on the mechanical performances of the composite. Few common measurement methods used for the void and moisture determination are discussed here. The aims of this short review, mainly to capture the trend ranging from the recent five years back and summarize the various studies and also to compare and conclude the most common method for the determination of the void and moisture content. This paper is mainly providing a baseline in the selection of the methods for the future work of the author’s work with regard to the reduction of the presence of voids and moisture occur during the impregnation process of fiber reinforced composites, especially when using natural-based fiber.

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