2 résultat(s) recherche sur le mot-clé '2'    

COMPUTATIONAL MODELING AND DRUG DISCOVERY IN THE CONTEXT OF HOST-PATHOGEN INTERACTIONS: APPLICATION TO SARS-COV-2 AND AGGREGATIBACTER ACTINOMYCETEMCOMITANS / HAKMI MOHAMMED

Public ISBD Titre : COMPUTATIONAL MODELING AND DRUG DISCOVERY IN THE CONTEXT OF HOST-PATHOGEN INTERACTIONS: APPLICATION TO SARS-COV-2 AND AGGREGATIBACTER ACTINOMYCETEMCOMITANS Type de document : thèse Auteurs : HAKMI MOHAMMED, Auteur Année de publication : 2023 Langues : Anglais (eng) Mots-clés : Host  Pathogen  Interaction  Computational Modeling  Molecular Dynamics  Molecular Docking  SARS-CoV-2  Aggregatibacter actinomycetemcomitans  Hôte  pathogène  interaction  modélisation informatique  dynamique moléculaire  amarrage moléculaire  SARS-CoV-2  Aggregatibacter actinomycetemcomitans  SARS-CoV-المضيف  الممرض  التفاعل  النمذجة المعلوماتية، الديناميكيات الجزيئية  الإرساء الجزيئي  2  Aggregatibacter actinomycetemcomitans Résumé : The study of host-pathogen interactions (HPIs) is crucial for understanding the mechanisms of infectious diseases and developing effective treatments. However, experimental methods for studying HPIs can be timeconsuming and yield limited results. As a result, computational methods have become an impressive tool for HPI prediction and modeling, given recent technological advances and the availability of vast amounts of genomic data. The aim of this thesis is to investigate proteomic interactions that offer insight into the critical molecular processes involved in infection mechanisms. Specifically, we focused on protein-protein interactions between the host and the pathogen, which present significant challenges related to infectious diseases and drug development. Using computational methods, we explored crucial drug targets from two human pathogens : SARS-CoV-2 and Aggregatibacter actinomycetemcomitans. For SARS-CoV-2, we examined two key proteins: the spike protein and the main protease. We investigated the interaction between the spike protein and the human ACE2 receptor and proposed novel compounds that disrupt this interaction and prevent the virus from infecting host cells. Additionally, we examined the use of existing antiviral agents to block the main protease's catalytic site and prevent its interaction with viral and possibly host proteins. For Aggregatibacter actinomycetemcomitans, we employed computational modeling and simulation to construct a high-resolution atomic model of its major virulence factor, the leukotoxin, and assessed its potential as a drug target. Furthermore, we established a computational model of the interaction between leukotoxin and its receptor LFA1, which could serve as a starting point for inhibitor design. Numéro (Thèse ou Mémoire) : D0112023 Président : KETTANI Anass Directeur : IBRAHIMI Azeddine ; Jaouad El HARTI Juge : EL JAOUDI Rachid Juge : Khalil HAMMANI Juge : Samira SERRAGUI ; Oumkeltoum ENNIBI COMPUTATIONAL MODELING AND DRUG DISCOVERY IN THE CONTEXT OF HOST-PATHOGEN INTERACTIONS: APPLICATION TO SARS-COV-2 AND AGGREGATIBACTER ACTINOMYCETEMCOMITANS [thèse] / HAKMI MOHAMMED, Auteur . - 2023. Langues : Anglais (eng) Mots-clés : Host  Pathogen  Interaction  Computational Modeling  Molecular Dynamics  Molecular Docking  SARS-CoV-2  Aggregatibacter actinomycetemcomitans  Hôte  pathogène  interaction  modélisation informatique  dynamique moléculaire  amarrage moléculaire  SARS-CoV-2  Aggregatibacter actinomycetemcomitans  SARS-CoV-المضيف  الممرض  التفاعل  النمذجة المعلوماتية، الديناميكيات الجزيئية  الإرساء الجزيئي  2  Aggregatibacter actinomycetemcomitans Résumé : The study of host-pathogen interactions (HPIs) is crucial for understanding the mechanisms of infectious diseases and developing effective treatments. However, experimental methods for studying HPIs can be timeconsuming and yield limited results. As a result, computational methods have become an impressive tool for HPI prediction and modeling, given recent technological advances and the availability of vast amounts of genomic data. The aim of this thesis is to investigate proteomic interactions that offer insight into the critical molecular processes involved in infection mechanisms. Specifically, we focused on protein-protein interactions between the host and the pathogen, which present significant challenges related to infectious diseases and drug development. Using computational methods, we explored crucial drug targets from two human pathogens : SARS-CoV-2 and Aggregatibacter actinomycetemcomitans. For SARS-CoV-2, we examined two key proteins: the spike protein and the main protease. We investigated the interaction between the spike protein and the human ACE2 receptor and proposed novel compounds that disrupt this interaction and prevent the virus from infecting host cells. Additionally, we examined the use of existing antiviral agents to block the main protease's catalytic site and prevent its interaction with viral and possibly host proteins. For Aggregatibacter actinomycetemcomitans, we employed computational modeling and simulation to construct a high-resolution atomic model of its major virulence factor, the leukotoxin, and assessed its potential as a drug target. Furthermore, we established a computational model of the interaction between leukotoxin and its receptor LFA1, which could serve as a starting point for inhibitor design. Numéro (Thèse ou Mémoire) : D0112023 Président : KETTANI Anass Directeur : IBRAHIMI Azeddine ; Jaouad El HARTI Juge : EL JAOUDI Rachid Juge : Khalil HAMMANI Juge : Samira SERRAGUI ; Oumkeltoum ENNIBI

Réservation

Réserver ce document

Exemplaires

Code barre	Cote	Support	Localisation	Section	Disponibilité
D0112023	WA	Thèse imprimé	Unité des Thèses et Mémoires	Doctorat SVS 2023	Disponible

MYCOBACTERIUM TUBERCULOSIS AND SARS-COV-2 GENOMIC ANALYSIS: INPUT INTO OUTBREAKS AND SURVEILLANCE INVESTIGATIONS / Mariem LAAMARTI 

Public ISBD Titre : MYCOBACTERIUM TUBERCULOSIS AND SARS-COV-2 GENOMIC ANALYSIS: INPUT INTO OUTBREAKS AND SURVEILLANCE INVESTIGATIONS Type de document : thèse Auteurs : Mariem LAAMARTI, Auteur Année de publication : 2021 Langues : Anglais (eng) Mots-clés : Mycobacterium Tuberculosis  SARS-Cov-2  Genomic analysis  Phylogeny  drug resistance  phylodynamic  sequencing  Mycobacterium Tuberculosis  SARS-Cov-2  Analyse genomique  Phylogenie  resistance aux antibiotique  , phylodynamique  sequencage  التحلیل الجینومي  النشوء والتطور  المقاومة  الدینامیكا النباتیة  SARS-CoV- المتفطرة السلیة  2  التسلسل Résumé : Comparative microbial genomics is increasingly used for high-resolution epidemiological investigation of infectious agents' sources, transmission dynamics and antimicrobial resistance. In Chapter II, We performed the sequencing and genomic characterization of M. Tuberculosis strains from Morocco to get insight into their genomic diversity, drug resistance, population structure and identify potential mutations associated with drug resistance. We conducted a whole-genome analysis of nine Morrocan M. tuberculosis isolates; we identied 25 known mutations and 14 novel mutations in drug-associated genes and provided experimental support for them. We found that all resistance and susceptible strains clustered with LAM9 and Haarlem, respectively, belonging to the Euro-American clade. The modelling of GyrA/GyrB mutations showed a decrease in the binding anity with levo oxacin. Chapter III addresses the comparative genomic of SARS-CoV-2 from Morocco to identify genetic variants as a crucial step in evaluating the spread in Morocco. This study revealed 108 mutations in their genomes. The analysis haplotype network suggests dierent sources of SARS-CoV-2 infection in Morocco. In Chapter IV, we collected SARS-CoV-2 genomes isolated from 80 countries.The results showed genotypes specic to geographic location. Moreover, evolution over time has demonstrated a mechanism of mutation co-accumulation, which might aect the severity and spread of the SARS-CoV-2 suggesting that a universal vaccine is more likely to be ecient for all strains. On the other hand, the selective pressure analysis revealed negatively selected residues that could be considered therapeutic targets. We have also created an inclusive unied database that lists all of the genetic variants of the SARS-CoV-2 genomes found in this study. Numéro (Thèse ou Mémoire) : D0112021 Président : Abdallah BADOU Directeur : Azeddine IBRAHIMI ; Samir SIAH Juge : Rachid ELJAOUDI Juge : Laila SBABOU ; Mohammed EL AZAMI EL IDRISSI ; Juge : Lahcen BELYAMANI ; Mouna OUAD MYCOBACTERIUM TUBERCULOSIS AND SARS-COV-2 GENOMIC ANALYSIS: INPUT INTO OUTBREAKS AND SURVEILLANCE INVESTIGATIONS [thèse] / Mariem LAAMARTI, Auteur . - 2021. Langues : Anglais (eng) Mots-clés : Mycobacterium Tuberculosis  SARS-Cov-2  Genomic analysis  Phylogeny  drug resistance  phylodynamic  sequencing  Mycobacterium Tuberculosis  SARS-Cov-2  Analyse genomique  Phylogenie  resistance aux antibiotique  , phylodynamique  sequencage  التحلیل الجینومي  النشوء والتطور  المقاومة  الدینامیكا النباتیة  SARS-CoV- المتفطرة السلیة  2  التسلسل Résumé : Comparative microbial genomics is increasingly used for high-resolution epidemiological investigation of infectious agents' sources, transmission dynamics and antimicrobial resistance. In Chapter II, We performed the sequencing and genomic characterization of M. Tuberculosis strains from Morocco to get insight into their genomic diversity, drug resistance, population structure and identify potential mutations associated with drug resistance. We conducted a whole-genome analysis of nine Morrocan M. tuberculosis isolates; we identied 25 known mutations and 14 novel mutations in drug-associated genes and provided experimental support for them. We found that all resistance and susceptible strains clustered with LAM9 and Haarlem, respectively, belonging to the Euro-American clade. The modelling of GyrA/GyrB mutations showed a decrease in the binding anity with levo oxacin. Chapter III addresses the comparative genomic of SARS-CoV-2 from Morocco to identify genetic variants as a crucial step in evaluating the spread in Morocco. This study revealed 108 mutations in their genomes. The analysis haplotype network suggests dierent sources of SARS-CoV-2 infection in Morocco. In Chapter IV, we collected SARS-CoV-2 genomes isolated from 80 countries.The results showed genotypes specic to geographic location. Moreover, evolution over time has demonstrated a mechanism of mutation co-accumulation, which might aect the severity and spread of the SARS-CoV-2 suggesting that a universal vaccine is more likely to be ecient for all strains. On the other hand, the selective pressure analysis revealed negatively selected residues that could be considered therapeutic targets. We have also created an inclusive unied database that lists all of the genetic variants of the SARS-CoV-2 genomes found in this study. Numéro (Thèse ou Mémoire) : D0112021 Président : Abdallah BADOU Directeur : Azeddine IBRAHIMI ; Samir SIAH Juge : Rachid ELJAOUDI Juge : Laila SBABOU ; Mohammed EL AZAMI EL IDRISSI ; Juge : Lahcen BELYAMANI ; Mouna OUAD

Réservation

Réserver ce document

Exemplaires

Code barre	Cote	Support	Localisation	Section	Disponibilité
D0112021	WA	Thèse imprimé	Unité des Thèses et Mémoires	Doctorat SVS 2021	Disponible

Documents numériques

D0112021 URL