The Structural Landscape of SARS-CoV-2 Main Protease: Hints for Inhibitor Search.

2020 ◽  
Author(s):  
Luigi Leonardo Palese
Keyword(s):  
Comparative Analysis ◽  
Global Health ◽  
Binding Site ◽  
Causative Agent ◽  
Data Set ◽  
Substrate Binding Site ◽  
Global Pandemic ◽  
Main Protease ◽  
Crystallographic Structures ◽  
Structural Aspects

In 2019, an outbreak occurred which resulted in a global pandemic. The causative agent of this serious global health threat was a coronavirus similar to the agent of SARS, referred to as SARS-CoV-2. In this work an analysis of the available structures of the SARS-CoV-2 main protease has been performed. From a data set of crystallographic structures the dynamics of the protease has been obtained. Furthermore, a comparative analysis of the structures of SARS-CoV-2 with those of the main protease of the coronavirus responsible of SARS (SARS-CoV) was carried out. The results of these studies suggest that, although main proteases of SARS-CoV and SARS-CoV-2 are similar at the backbone level, some plasticity at the substrate binding site can be observed. The consequences of these structural aspects on the search for effective inhibitors of these enzymes are discussed, with a focus on already known compounds. The results obtained show that compounds containing an oxirane ring could be considered as inhibitors of the main protease of SARS-CoV-2.

scholarly journals The Structural Landscape of SARS-CoV-2 Main Protease: Hints for Inhibitor Search.

2020 ◽  
Author(s):  
Luigi Leonardo Palese
Keyword(s):  
Comparative Analysis ◽  
Global Health ◽  
Binding Site ◽  
Causative Agent ◽  
Data Set ◽  
Substrate Binding Site ◽  
Global Pandemic ◽  
Main Protease ◽  
Crystallographic Structures ◽  
Structural Aspects

In 2019, an outbreak occurred which resulted in a global pandemic. The causative agent of this serious global health threat was a coronavirus similar to the agent of SARS, referred to as SARS-CoV-2. In this work an analysis of the available structures of the SARS-CoV-2 main protease has been performed. From a data set of crystallographic structures the dynamics of the protease has been obtained. Furthermore, a comparative analysis of the structures of SARS-CoV-2 with those of the main protease of the coronavirus responsible of SARS (SARS-CoV) was carried out. The results of these studies suggest that, although main proteases of SARS-CoV and SARS-CoV-2 are similar at the backbone level, some plasticity at the substrate binding site can be observed. The consequences of these structural aspects on the search for effective inhibitors of these enzymes are discussed, with a focus on already known compounds. The results obtained show that compounds containing an oxirane ring could be considered as inhibitors of the main protease of SARS-CoV-2.

scholarly journals Computational estimation of potential inhibitors from known drugs against the main protease of SARS-CoV-2

RSC Advances ◽  
2021 ◽  
Vol 11 (28) ◽  
pp. 17478-17486
Author(s):  
Nguyen Minh Tam ◽  
Minh Quan Pham ◽  
Nguyen Xuan Ha ◽  
Pham Cam Nam ◽  
Huong Thi Thu Phung
Keyword(s):  
Binding Site ◽  
Substrate Binding ◽  
Substrate Binding Site ◽  
Computational Estimation ◽  
Main Protease ◽  
Critical Residues ◽  
Approved Drugs ◽  
Potential Inhibitors

Approved drugs predicted to interact with critical residues in the substrate-binding site of SARS-CoV-2 Mpro can be promising inhibitors.

scholarly journals Neurological Complications in COVID-19: Implications on International Health Security and Possible Interventions of Phytochemicals

2021 ◽  
Author(s):  
Johnson Olaleye Oladele ◽  
Oluwaseun Titilope Oladele ◽  
Oyedotun M. Oyeleke ◽  
Adenike T. Oladiji
Keyword(s):  
Global Health ◽  
Case Reports ◽  
Emerging Infectious Diseases ◽  
International Health ◽  
Well Being ◽  
Neurological Complications ◽  
Health Security ◽  
Beneficial Effects ◽  
Global Pandemic ◽  
Main Protease

Global health security or international health security (IHS) includes any natural or man-made phenomenon that challenged human health and well-being including emerging infectious diseases such as the current global pandemic: COVID-19. Since the sudden outburst of COVID-19 pandemic in 2019, many COVID-19 patients have exhibited neurological symptoms and signs. Till now, there is no known effective established drug against the highly contagious COVID-19 infection despite the frightening associated mortality rate. This chapter aims to present the mechanism of action of coronavirus-2 (SARS-CoV-2), the clinical neurological manifestations displayed by COVID-19 patients, impact on the global health system and present phytochemicals with neuroprotective ability that can offer beneficial effects against COVID-19 mediated neuropathology. Reports from COVID-19 clinical studies, case reports, and other related literature were evaluated. Neurological complications of COVID-19 include anosmia, acute cerebrovascular disease, acute disseminated post-infectious encephalomyelitis, encephalitis, etc. Also, SARS-CoV-2 соuld be a neurotropic vіruѕ due to its iѕоlаtіоn from сеrеbrоѕріnаl fluіd. Multірlе nеurоlоgісаl dаmаgе displayed by COVID-19 patients might be due to hyperinflammation associated with SARS-CoV-2 infections. Kolaviron, resveratrol, vernodalin, vernodalol, and apigenin are natural phytochemicals with proven anti-inflammatory and therapeutic properties that could extenuate the adverse effects of COVID-19. The phytochemicals have been documented to suppress JNK and MAPK pathways which are essential in the pathogenesis of COVID-19. They also showed significant inhibitory activities against SARS-CoV-2 main protease. Taken together, these phytochemicals may offer neuroprotective benefits against COVID-19 mediated neuropathology and suppress the burden of the pandemic on IHS.

Is the Rigidity of SARS-CoV-2 Spike Receptor-Binding Motif the Hallmark for Its Enhanced Infectivity and Pathogenesis?

2020 ◽  
Author(s):  
Angelo Spinello ◽  
Andrea Saltalamacchia ◽  
Alessandra Magistrato
Keyword(s):  
Health Economic ◽  
Global Health ◽  
Receptor Binding ◽  
Binding Motif ◽  
Spike Glycoprotein ◽  
High Affinity ◽  
Global Pandemic ◽  
Medical Countermeasures ◽  
High Infectivity ◽  
Human Receptor

<p>The latest outbreak of a new pathogenic coronavirus (SARS-CoV-2) is provoking a global health, economic and societal crisis. All-atom simulations enabled us to uncover the key molecular traits underlying the high affinity of SARS-CoV-2 spike glycoprotein towards its human receptor, providing a rationale to its high infectivity. Harnessing this knowledge can boost developing effective medical countermeasures to fight the current global pandemic.</p>

Comprehensive in silico Study of GLUT10: Prediction of Possible Substrate Binding Sites and Interacting Molecules

2020 ◽  
Vol 21 (2) ◽  
pp. 117-130 ◽  
Author(s):  
Mohammad J. Hosen ◽  
Mahmudul Hasan ◽  
Sourav Chakraborty ◽  
Ruhshan A. Abir ◽  
Abdullah Zubaer ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Binding Site ◽  
Glucose Transporter ◽  
Substrate Binding ◽  
Mutation Screening ◽  
Homology Model ◽  
Connective Tissue Disorder ◽  
Crystallographic Structure ◽  
Substrate Binding Site

Objectives: The Arterial Tortuosity Syndrome (ATS) is an autosomal recessive connective tissue disorder, mainly characterized by tortuosity and stenosis of the arteries with a propensity towards aneurysm formation and dissection. It is caused by mutations in the SLC2A10 gene that encodes the facilitative glucose transporter GLUT10. The molecules transported by and interacting with GLUT10 have still not been unambiguously identified. Hence, the study attempts to identify both the substrate binding site of GLUT10 and the molecules interacting with this site. Methods: As High-resolution X-ray crystallographic structure of GLUT10 was not available, 3D homology model of GLUT10 in open conformation was constructed. Further, molecular docking and bioinformatics investigation were employed. Results and Discussion: Blind docking of nine reported potential in vitro substrates with this 3D homology model revealed that substrate binding site is possibly made with PRO531, GLU507, GLU437, TRP432, ALA506, LEU519, LEU505, LEU433, GLN525, GLN510, LYS372, LYS373, SER520, SER124, SER533, SER504, SER436 amino acid residues. Virtual screening of all metabolites from the Human Serum Metabolome Database and muscle metabolites from Human Metabolite Database (HMDB) against the GLUT10 revealed possible substrates and interacting molecules for GLUT10, which were found to be involved directly or partially in ATS progression or different arterial disorders. Reported mutation screening revealed that a highly emergent point mutation (c. 1309G>A, p. Glu437Lys) is located in the predicted substrate binding site region. Conclusion: Virtual screening expands the possibility to explore more compounds that can interact with GLUT10 and may aid in understanding the mechanisms leading to ATS.

Comparative Analysis of Machine Learning Techniques Using Predictive Modeling

2020 ◽  
Vol 13 ◽  
Author(s):  
Ritu Khandelwal ◽  
Hemlata Goyal ◽  
Rajveer Singh Shekhawat
Keyword(s):  
Machine Learning ◽  
Comparative Analysis ◽  
Data Science ◽  
Training Data ◽  
Machine Learning Techniques ◽  
Future Trends ◽  
Data Set ◽  
Learning Stage ◽  
Learning Techniques ◽  
Different Types

Introduction: Machine learning is an intelligent technology that works as a bridge between businesses and data science. With the involvement of data science, the business goal focuses on findings to get valuable insights on available data. The large part of Indian Cinema is Bollywood which is a multi-million dollar industry. This paper attempts to predict whether the upcoming Bollywood Movie would be Blockbuster, Superhit, Hit, Average or Flop. For this Machine Learning techniques (classification and prediction) will be applied. To make classifier or prediction model first step is the learning stage in which we need to give the training data set to train the model by applying some technique or algorithm and after that different rules are generated which helps to make a model and predict future trends in different types of organizations. Methods: All the techniques related to classification and Prediction such as Support Vector Machine(SVM), Random Forest, Decision Tree, Naïve Bayes, Logistic Regression, Adaboost, and KNN will be applied and try to find out efficient and effective results. All these functionalities can be applied with GUI Based workflows available with various categories such as data, Visualize, Model, and Evaluate. Result: To make classifier or prediction model first step is learning stage in which we need to give the training data set to train the model by applying some technique or algorithm and after that different rules are generated which helps to make a model and predict future trends in different types of organizations Conclusion: This paper focuses on Comparative Analysis that would be performed based on different parameters such as Accuracy, Confusion Matrix to identify the best possible model for predicting the movie Success. By using Advertisement Propaganda, they can plan for the best time to release the movie according to the predicted success rate to gain higher benefits. Discussion: Data Mining is the process of discovering different patterns from large data sets and from that various relationships are also discovered to solve various problems that come in business and helps to predict the forthcoming trends. This Prediction can help Production Houses for Advertisement Propaganda and also they can plan their costs and by assuring these factors they can make the movie more profitable.

scholarly journals Experiences of Intimate Partner Violence during Lockdown and the COVID-19 Pandemic

2021 ◽  
Author(s):  
Minna Lyons ◽  
Gayle Brewer
Keyword(s):  
Intimate Partner Violence ◽  
Global Health ◽  
Thematic Analysis ◽  
Partner Violence ◽  
Intimate Partner ◽  
Substantial Impact ◽  
Female Victims ◽  
Global Pandemic ◽  
Qualitative Thematic Analysis ◽  
Service Disruption

AbstractPrevious studies have demonstrated that there is an increase in Intimate Partner Violence (IPV) during times of crisis (e.g., financial, environmental, or socio-political situations). The COVID-19 pandemic has triggered an unprecedented global health and financial tragedy, but research is yet to establish exactly how the situation may impact on IPV. The present study investigates victims’ experience of IPV during lockdown and the COVID-19 pandemic. We report a qualitative thematic analysis of 50 discussion forum posts written by victims of IPV. Of these, 48 forum posts were written by female victims of male perpetrated violence. All forum posts were obtained from the popular online platform, Reddit. We identified four themes associated with IPV victims’ experiences during lockdown and the global pandemic: (i) Use of COVID-19 by the Abuser, (ii) Service Disruption, (iii) Preparation to Leave, and (iv) Factors Increasing Abuse or Distress. The COVID-19 pandemic has had a substantial impact on those living with IPV, often increasing the severity of IPV experienced. The experiences of those affected by IPV during this period inform interventions and the guidance and support provided to IPV victims during times of crisis.

Intuitionistic fuzzy two-factor variance analysis of movie ticket sales

2021 ◽  
pp. 1-11
Author(s):  
Velichka Traneva ◽  
Stoyan Tranev
Keyword(s):  
Comparative Analysis ◽  
Real Data ◽  
Intuitionistic Fuzzy Sets ◽  
Real Numbers ◽  
Data Set ◽  
Important Method ◽  
Ticket Sales ◽  
Intuitionistic Fuzzy ◽  
The One ◽  
First Time

Analysis of variance (ANOVA) is an important method in data analysis, which was developed by Fisher. There are situations when there is impreciseness in data In order to analyze such data, the aim of this paper is to introduce for the first time an intuitionistic fuzzy two-factor ANOVA (2-D IFANOVA) without replication as an extension of the classical ANOVA and the one-way IFANOVA for a case where the data are intuitionistic fuzzy rather than real numbers. The proposed approach employs the apparatus of intuitionistic fuzzy sets (IFSs) and index matrices (IMs). The paper also analyzes a unique set of data on daily ticket sales for a year in a multiplex of Cinema City Bulgaria, part of Cineworld PLC Group, applying the two-factor ANOVA and the proposed 2-D IFANOVA to study the influence of “ season ” and “ ticket price ” factors. A comparative analysis of the results, obtained after the application of ANOVA and 2-D IFANOVA over the real data set, is also presented.

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