| Titre : | SINGLE NUCLEOTIDE POLYMORPHISMS MAY IMPACT SARS-COV-2 INFECTIVITY AND THE DEVELOPMENT OF DRUGS AND VACCINES IN THE NEAR FUTURE. | | Type de document : | thèse | | Auteurs : | Laila EL MASSARI, Auteur | | Année de publication : | 2020 | | Langues : | Anglais (eng) | | Mots-clés : | COVID-19 SARS-CoV-2 Genomic variation Mutations SNPs COVID-19 SARS-CoV-2 Variation génomique Mutations SNPs | | Résumé : | General Introduction
Following its immergence in late December 2019, the recent Coronavirus (COVID-19) outbreak in Wuhan China has spread around the whole planet, touching millions of people in more than 220 countries and territories leading to more than 59 million infection cases and 1 404 542 deaths as of November 25, 2020 making it the largest Coronavirus pandemic in both scale and geographical region to date.
Introduction to the Problematic
In order to develop an effective treatment for the novel SARS-Cov-2, studying the genomic variation and the virus evolution over time becomes a priority in the eradication of the virus.
Objective
To study and follow the appearance and accumulation of mutations or SNPs in SARS-CoV-2 in order to understand the virus’s changes causing increase in continuing mortality and morbidity and that may affect the developing and effectiveness of drugs and vaccines in the near future.
Materials and Methods
In this study, a total 1050 sequences of the SARS-Cov-2 full-length genome obtained from 4 countries during the first eight months after the onset of this virus were used to study the genomic variation of SARS-Cov-2.
Results and Conclusion Using genomic analysis we identified a total of 6 SNPs in different vital proteins of SARS-Cov-2. 4 common mutations were frequent between Morocco, USA, Italy and France. The first common SNP in the SARS-CoV-2 genome is the D614G mutation on the spike protein. It results from an adenine to guanine (A to G) mutation at position 23403 and causes a flap on the tip of one spike to pop open, allowing the virus to infect cells more efficiently but also creating a pathway to the virus' vulnerable core. The D614G change is almost always accompanied by three other mutations; C-to-T mutation in the 5’UTR at position 241, which lies in the leader sequence of the SARS-CoV-2 viral genome and has been implicated to higher mortality and/ or infectivity of the virus. Silent C-to-T mutation in the nsp3 at position 3037 and C-to-T mutation at position 14408 in an amino acid change in RNA-dependent
Master in Medical Biotechnology Page 5
RNA polymerase (RdRp). Combined, these four co-mutations probably can confer increased transmissibility of the virus and may also be correlated with the critical condition in Italy and US. Also, many nucleotide deletions and insertions have been noticed in the genome as well. These results are of great importance for the assessment of enhanced antiviral virulence and efficacy, and give rise to potential causes of overwhelming SARS-CoV-2 mutations. | | Numéro (Thèse ou Mémoire) : | MM0272020 | | Président : | Azeddine IBRAHIMI | | Directeur : | Abdelmounim ESSABAR | | Juge : | Kaoutar EL KHATTABI | | Juge : | Souad KARTTI |
SINGLE NUCLEOTIDE POLYMORPHISMS MAY IMPACT SARS-COV-2 INFECTIVITY AND THE DEVELOPMENT OF DRUGS AND VACCINES IN THE NEAR FUTURE. [thèse] / Laila EL MASSARI, Auteur . - 2020. Langues : Anglais ( eng) | Mots-clés : | COVID-19 SARS-CoV-2 Genomic variation Mutations SNPs COVID-19 SARS-CoV-2 Variation génomique Mutations SNPs | | Résumé : | General Introduction
Following its immergence in late December 2019, the recent Coronavirus (COVID-19) outbreak in Wuhan China has spread around the whole planet, touching millions of people in more than 220 countries and territories leading to more than 59 million infection cases and 1 404 542 deaths as of November 25, 2020 making it the largest Coronavirus pandemic in both scale and geographical region to date.
Introduction to the Problematic
In order to develop an effective treatment for the novel SARS-Cov-2, studying the genomic variation and the virus evolution over time becomes a priority in the eradication of the virus.
Objective
To study and follow the appearance and accumulation of mutations or SNPs in SARS-CoV-2 in order to understand the virus’s changes causing increase in continuing mortality and morbidity and that may affect the developing and effectiveness of drugs and vaccines in the near future.
Materials and Methods
In this study, a total 1050 sequences of the SARS-Cov-2 full-length genome obtained from 4 countries during the first eight months after the onset of this virus were used to study the genomic variation of SARS-Cov-2.
Results and Conclusion Using genomic analysis we identified a total of 6 SNPs in different vital proteins of SARS-Cov-2. 4 common mutations were frequent between Morocco, USA, Italy and France. The first common SNP in the SARS-CoV-2 genome is the D614G mutation on the spike protein. It results from an adenine to guanine (A to G) mutation at position 23403 and causes a flap on the tip of one spike to pop open, allowing the virus to infect cells more efficiently but also creating a pathway to the virus' vulnerable core. The D614G change is almost always accompanied by three other mutations; C-to-T mutation in the 5’UTR at position 241, which lies in the leader sequence of the SARS-CoV-2 viral genome and has been implicated to higher mortality and/ or infectivity of the virus. Silent C-to-T mutation in the nsp3 at position 3037 and C-to-T mutation at position 14408 in an amino acid change in RNA-dependent
Master in Medical Biotechnology Page 5
RNA polymerase (RdRp). Combined, these four co-mutations probably can confer increased transmissibility of the virus and may also be correlated with the critical condition in Italy and US. Also, many nucleotide deletions and insertions have been noticed in the genome as well. These results are of great importance for the assessment of enhanced antiviral virulence and efficacy, and give rise to potential causes of overwhelming SARS-CoV-2 mutations. | | Numéro (Thèse ou Mémoire) : | MM0272020 | | Président : | Azeddine IBRAHIMI | | Directeur : | Abdelmounim ESSABAR | | Juge : | Kaoutar EL KHATTABI | | Juge : | Souad KARTTI |
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