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Article ; Online: Curcumin-Synthetic Analogs Library Screening by Docking and Quantitative Structure-Activity Relationship Studies for AXL Tyrosine Kinase Inhibition in Cancers.

Ghrifi, Fatima / Allam, Loubna / Wiame, Lakhlili / Ibrahimi, Azeddine

Journal of computational biology : a journal of computational molecular cell biology

2019 Volume 26, Issue 10, Page(s) 1156–1167

Abstract: AXL is an important drug target for cancers. Two-dimensional quantitative structure-activity relationship (2D-QSAR) tests were performed to elucidate a relationship between molecular structures and the activity of a series of 400 curcumin derivatives ... ...

Abstract	AXL is an important drug target for cancers. Two-dimensional quantitative structure-activity relationship (2D-QSAR) tests were performed to elucidate a relationship between molecular structures and the activity of a series of 400 curcumin derivatives subjected to AXL kinase by ATP competition in the catalytic site. The partial least square regression method implanted in molecular operating environment software was applied to develop QSAR models, which were further validated for statistical significance by internal and external validation. The best model has proven to be statistically robust with a good predictive correlation of
MeSH term(s)	Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Curcumin/analogs & derivatives ; Curcumin/pharmacology ; Humans ; Molecular Docking Simulation ; Neoplasms/drug therapy ; Neoplasms/enzymology ; Protein Kinase Inhibitors/chemistry ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins/antagonists & inhibitors ; Proto-Oncogene Proteins/metabolism ; Quantitative Structure-Activity Relationship ; Receptor Protein-Tyrosine Kinases/antagonists & inhibitors ; Receptor Protein-Tyrosine Kinases/metabolism
Chemical Substances	Antineoplastic Agents ; Protein Kinase Inhibitors ; Proto-Oncogene Proteins ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; axl receptor tyrosine kinase (EC 2.7.10.1) ; Curcumin (IT942ZTH98)
Language	English
Publishing date	2019-06-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2030900-4
ISSN	1557-8666 ; 1066-5277
ISSN (online)	1557-8666
ISSN	1066-5277
DOI	10.1089/cmb.2019.0052
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Targeting the GRP78-Dependant SARS-CoV-2 Cell Entry by Peptides and Small Molecules

Allam, Loubna Ghrifi Fatima Mohammed Hakmi El Hafidi Naima El Jaoudi Rachid El Harti Jaouad Lmimouni Badreddine Belyamani Lahcen Ibrahimi Azeddine

Bioinformatics & Biology Insights

Abstract: The global burden of infections and the rapid spread of viral diseases show the need for new approaches in the prevention and development of effective therapies To this end, we aimed to explore novel inhibitor compounds that can stop replication or ... ...

Abstract	The global burden of infections and the rapid spread of viral diseases show the need for new approaches in the prevention and development of effective therapies To this end, we aimed to explore novel inhibitor compounds that can stop replication or decrease the viral load of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there is currently no approved treatment Besides using the angiotensin-converting enzyme (ACE2) receptor as a main gate, the CoV-2 can bind to the glucose-regulating protein 78 (GRP78) receptor to get into the cells to start an infection Here, we report potential inhibitors comprising small molecules and peptides that could interfere with the interaction of SARS-CoV-2 and its target cells by blocking the recognition of the GRP78 cellular receptor by the viral Spike protein These inhibitors were discovered through an approach of in silico screening of available databases of bioactive peptides and polyphenolic compounds and the analysis of their docking modes This process led to the selection of 9 compounds with optimal binding affinities to the target sites The peptides (satpdb18674, satpdb18446, satpdb12488, satpdb14438, and satpdb28899) act on regions III and IV of the viral Spike protein and on its binding sites in GRP78 However, 4 polyphenols such as epigallocatechin gallate (EGCG), homoeriodictyol, isorhamnetin, and curcumin interact, in addition to the Spike protein and its binding sites in GRP78, with the ATPase domain of GRP78 Our work demonstrates that there are at least 2 approaches to block the spread of SARS-CoV-2 by preventing its fusion with the host cells via GRP78 [ABSTRACT FROM AUTHOR] Copyright of Bioinformatics & Biology Insights is the property of Sage Publications Inc and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #892352
Database	COVID19

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Article: Significant Association of Polymorphisms in the TCF7L2 Gene with a Higher Risk of Type 2 Diabetes in a Moroccan Population.

Elhourch, Sarah / Arrouchi, Housna / Mekkaoui, Nour / Allou, Younes / Ghrifi, Fatima / Allam, Loubna / Elhafidi, Naima / Belyamani, Lahcen / Ibrahimi, Azeddine / Elomri, Naoual / Eljaoudi, Rachid

Journal of personalized medicine

2021 Volume 11, Issue 6

Abstract: Background and aims: Several studies have shown that genetic polymorphisms of the transcription factor 7-like 2 (TCF7L2) are highly associated with the development of type 2 diabetes mellitus (T2DM) and its associated complications in several ... ...

Abstract	Background and aims: Several studies have shown that genetic polymorphisms of the transcription factor 7-like 2 (TCF7L2) are highly associated with the development of type 2 diabetes mellitus (T2DM) and its associated complications in several populations. The aim of our study was to investigate the association of the rs7903146 (C/T) and rs12255372 (G/T) polymorphism in the TCF7L2 gene with the risk of developing T2DM in the Moroccan population. Material and methods: A total of 150 T2DM patients and 100 healthy controls were recruited for various anthropometric, biochemical and genetic parameters. Genotyping was performed by using Real Time-PCR. The frequency of genotypes, alleles, anthropometric measures, glycemia, glycated hemoglobin (HbA1c) were evaluated in patients and control, while lipid profile was available only for T2DM group. Results: Glycemia, HbA1c and body mass index (BMI) were significantly higher in T2DM group than control. Analysis of the distribution of the TCF7L2 rs7903146 genotype and allele revealed that the TT genotype was more frequent in T2DM group (24.0%) than in healthy controls (5%) (OR = 4.08, 95% confidence interval (CI = 1.95-11.80, Conclusion: The present study confirmed a significant association of the TCF7L2 gene (rs7903146 (C/T) and rs12255372 (G/T) polymorphisms with a higher risk to T2DM in the Moroccan population. No significant difference in respect to anthropometric and metabolic parameters between different genotypes.
Language	English
Publishing date	2021-05-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm11060461
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Article ; Online: AKT1 Polymorphism (rs10138227) and Risk of Colorectal Cancer in Moroccan Population: A Case Control Study.

Allam, Loubna / Arrouchi, Housna / Ghrifi, Fatima / El Khazraji, Abdelhak / Kandoussi, Ilham / Bendahou, Mohammed Amine / El Amri, Hamid / El Absi, Mohamed / Ibrahimi, Azeddine

Asian Pacific journal of cancer prevention : APJCP

2020 Volume 21, Issue 11, Page(s) 3165–3170

Abstract: Background: LMTK3 and AKT1 each have a role in carcinogenesis and tumor progression. The analysis of single nucleotide polymorphisms of AKT1 and LMTK3 could lead to more complete and accurate risk estimates for colorectal cancer.: Aim: We evaluated ... ...

Abstract	Background: LMTK3 and AKT1 each have a role in carcinogenesis and tumor progression. The analysis of single nucleotide polymorphisms of AKT1 and LMTK3 could lead to more complete and accurate risk estimates for colorectal cancer. Aim: We evaluated the association between single nucleotide polymorphisms (SNPs) of AKT1 and LMTK3 and the risk of colorectal cancer in a case-control study in Moroccan population. Methods: Genomic DNA from 70 colorectal cancer patients and 50 healthy control subjects was extracted from whole blood. Genotyping was performed by direct sequencing after polymerase chain reactions for the 7 SNPs (AKT1rs1130214G/T, AKT1rs10138227C/T, AKT1rs3730358C/T, AKT1rs1000559097G/A, AKT1rs2494737A/T, LMTK3rs8108419G/A, and LMTK3rs9989661A/G.). Study subjects provided detailed information during the collection. All P values come from bilateral tests. Results: In the logistic regression analysis, a significantly high risk of colorectal cancer was associated with TC/TT genotypes of rs10138227 with adjusted odds ratio [OR] equal to 2.82 and 95% confidence interval [CI] of 1.15 to 6.91. Conclusion: Our results suggest that the SNP AKT1rs10138227 could affect susceptibility to CRC, probably by modulating the transcriptional activity of AKT1. However, larger independent studies are needed to validate our results.
MeSH term(s)	Biomarkers, Tumor/genetics ; Case-Control Studies ; Colorectal Neoplasms/epidemiology ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Female ; Follow-Up Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Middle Aged ; Morocco/epidemiology ; Polymorphism, Single Nucleotide ; Prognosis ; Proto-Oncogene Proteins c-akt/genetics ; Risk Factors
Chemical Substances	Biomarkers, Tumor ; AKT1 protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2020-11-01
Publishing country	Thailand
Document type	Journal Article
ZDB-ID	2218955-5
ISSN	2476-762X ; 1513-7368
ISSN (online)	2476-762X
ISSN	1513-7368
DOI	10.31557/APJCP.2020.21.11.3165
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Targeting the GRP78-Dependant SARS-CoV-2 Cell Entry by Peptides and Small Molecules.

Allam, Loubna / Ghrifi, Fatima / Mohammed, Hakmi / El Hafidi, Naima / El Jaoudi, Rachid / El Harti, Jaouad / Lmimouni, Badreddine / Belyamani, Lahcen / Ibrahimi, Azeddine

Bioinformatics and biology insights

2020 Volume 14, Page(s) 1177932220965505

Abstract: The global burden of infections and the rapid spread of viral diseases show the need for new approaches in the prevention and development of effective therapies. To this end, we aimed to explore novel inhibitor compounds that can stop replication or ... ...

Abstract	The global burden of infections and the rapid spread of viral diseases show the need for new approaches in the prevention and development of effective therapies. To this end, we aimed to explore novel inhibitor compounds that can stop replication or decrease the viral load of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there is currently no approved treatment. Besides using the angiotensin-converting enzyme (ACE2) receptor as a main gate, the CoV-2 can bind to the glucose-regulating protein 78 (GRP78) receptor to get into the cells to start an infection. Here, we report potential inhibitors comprising small molecules and peptides that could interfere with the interaction of SARS-CoV-2 and its target cells by blocking the recognition of the GRP78 cellular receptor by the viral Spike protein. These inhibitors were discovered through an approach of in silico screening of available databases of bioactive peptides and polyphenolic compounds and the analysis of their docking modes. This process led to the selection of 9 compounds with optimal binding affinities to the target sites. The peptides (satpdb18674, satpdb18446, satpdb12488, satpdb14438, and satpdb28899) act on regions III and IV of the viral Spike protein and on its binding sites in GRP78. However, 4 polyphenols such as epigallocatechin gallate (EGCG), homoeriodictyol, isorhamnetin, and curcumin interact, in addition to the Spike protein and its binding sites in GRP78, with the ATPase domain of GRP78. Our work demonstrates that there are at least 2 approaches to block the spread of SARS-CoV-2 by preventing its fusion with the host cells via GRP78.
Keywords	covid19
Language	English
Publishing date	2020-10-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2423808-9
ISSN	1177-9322
ISSN	1177-9322
DOI	10.1177/1177932220965505
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Article: Genomic Diversity and Hotspot Mutations in 30,983 SARS-CoV-2 Genomes: Moving Toward a Universal Vaccine for the “Confined Virus”?

Alouane, Tarek / Laamarti, Meriem / Essabbar, Abdelomunim / Hakmi, Mohammed / Bouricha, El Mehdi / Chemao-Elfihri, M. W / Kartti, Souad / Boumajdi, Nasma / Bendani, Houda / Laamarti, Rokia / Ghrifi, Fatima / Allam, Loubna / Aanniz, Tarik / Ouadghiri, Mouna / El Hafidi, Naima / El Jaoudi, Rachid / Benrahma, Houda / Attar, Jalil El / Mentag, Rachid /

Sbabou, Laila / Nejjari, Chakib / Amzazi, Saaid / Belyamani, Lahcen / Ibrahimi, Azeddine

Pathogens. 2020 Oct. 10, v. 9, no. 10

2020

Abstract: The COVID-19 pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. Understanding and monitoring the genetic evolution of the virus, its geographical characteristics, and its stability are particularly important for controlling ... ...

Abstract	The COVID-19 pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. Understanding and monitoring the genetic evolution of the virus, its geographical characteristics, and its stability are particularly important for controlling the spread of the disease and especially for the development of a universal vaccine covering all circulating strains. From this perspective, we analyzed 30,983 complete SARS-CoV-2 genomes from 79 countries located in the six continents and collected from 24 December 2019, to 13 May 2020, according to the GISAID database. Our analysis revealed the presence of 3206 variant sites, with a uniform distribution of mutation types in different geographic areas. Remarkably, a low frequency of recurrent mutations has been observed; only 169 mutations (5.27%) had a prevalence greater than 1% of genomes. Nevertheless, fourteen non-synonymous hotspot mutations (>10%) have been identified at different locations along the viral genome; eight in ORF1ab polyprotein (in nsp2, nsp3, transmembrane domain, RdRp, helicase, exonuclease, and endoribonuclease), three in nucleocapsid protein, and one in each of three proteins: Spike, ORF3a, and ORF8. Moreover, 36 non-synonymous mutations were identified in the receptor-binding domain (RBD) of the spike protein with a low prevalence (<1%) across all genomes, of which only four could potentially enhance the binding of the SARS-CoV-2 spike protein to the human ACE2 receptor. These results along with intra-genomic divergence of SARS-CoV-2 could indicate that unlike the influenza virus or HIV viruses, SARS-CoV-2 has a low mutation rate which makes the development of an effective global vaccine very likely.
Keywords	Coronavirus infections ; Orthomyxoviridae ; databases ; disease transmission ; frequency ; genetic variation ; genome ; humans ; monitoring ; mutation ; mutation rate ; nucleocapsid proteins ; pandemic ; pathogens ; polyproteins ; prevalence ; strains ; vaccines ; viruses ; China
Language	English
Dates of publication	2020-1010
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-light
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens9100829
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Targeting the GRP78-Dependant SARS-CoV-2 Cell Entry by Peptides and Small Molecules

Allam, Loubna / Ghrifi, Fatima / Mohammed, Hakmi / El Hafidi, Naima / El Jaoudi, Rachid / El Harti, Jaouad / Lmimouni, Badreddine / Belyamani, Lahcen / Ibrahimi, Azeddine

Bioinformatics and Biology Insights

2020 Volume 14, Page(s) 117793222096550

Abstract	The global burden of infections and the rapid spread of viral diseases show the need for new approaches in the prevention and development of effective therapies. To this end, we aimed to explore novel inhibitor compounds that can stop replication or decrease the viral load of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there is currently no approved treatment. Besides using the angiotensin-converting enzyme (ACE2) receptor as a main gate, the CoV-2 can bind to the glucose-regulating protein 78 (GRP78) receptor to get into the cells to start an infection. Here, we report potential inhibitors comprising small molecules and peptides that could interfere with the interaction of SARS-CoV-2 and its target cells by blocking the recognition of the GRP78 cellular receptor by the viral Spike protein. These inhibitors were discovered through an approach of in silico screening of available databases of bioactive peptides and polyphenolic compounds and the analysis of their docking modes. This process led to the selection of 9 compounds with optimal binding affinities to the target sites. The peptides (satpdb18674, satpdb18446, satpdb12488, satpdb14438, and satpdb28899) act on regions III and IV of the viral Spike protein and on its binding sites in GRP78. However, 4 polyphenols such as epigallocatechin gallate (EGCG), homoeriodictyol, isorhamnetin, and curcumin interact, in addition to the Spike protein and its binding sites in GRP78, with the ATPase domain of GRP78. Our work demonstrates that there are at least 2 approaches to block the spread of SARS-CoV-2 by preventing its fusion with the host cells via GRP78.
Keywords	Biochemistry ; Applied Mathematics ; Molecular Biology ; Computational Mathematics ; Computer Science Applications ; covid19
Language	English
Publisher	SAGE Publications
Publishing country	us
Document type	Article ; Online
ZDB-ID	2423808-9
ISSN	1177-9322
ISSN	1177-9322
DOI	10.1177/1177932220965505
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Genomic Diversity and Hotspot Mutations in 30,983 SARS-CoV-2 Genomes: Moving Toward a Universal Vaccine for the "Confined Virus"?

Alouane, Tarek / Laamarti, Meriem / Essabbar, Abdelomunim / Hakmi, Mohammed / Bouricha, El Mehdi / Chemao-Elfihri, M W / Kartti, Souad / Boumajdi, Nasma / Bendani, Houda / Laamarti, Rokia / Ghrifi, Fatima / Allam, Loubna / Aanniz, Tarik / Ouadghiri, Mouna / El Hafidi, Naima / El Jaoudi, Rachid / Benrahma, Houda / Attar, Jalil El / Mentag, Rachid /

Sbabou, Laila / Nejjari, Chakib / Amzazi, Saaid / Belyamani, Lahcen / Ibrahimi, Azeddine

Pathogens (Basel, Switzerland)

2020 Volume 9, Issue 10

Abstract	The COVID-19 pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. Understanding and monitoring the genetic evolution of the virus, its geographical characteristics, and its stability are particularly important for controlling the spread of the disease and especially for the development of a universal vaccine covering all circulating strains. From this perspective, we analyzed 30,983 complete SARS-CoV-2 genomes from 79 countries located in the six continents and collected from 24 December 2019, to 13 May 2020, according to the GISAID database. Our analysis revealed the presence of 3206 variant sites, with a uniform distribution of mutation types in different geographic areas. Remarkably, a low frequency of recurrent mutations has been observed; only 169 mutations (5.27%) had a prevalence greater than 1% of genomes. Nevertheless, fourteen non-synonymous hotspot mutations (>10%) have been identified at different locations along the viral genome; eight in ORF1ab polyprotein (in nsp2, nsp3, transmembrane domain, RdRp, helicase, exonuclease, and endoribonuclease), three in nucleocapsid protein, and one in each of three proteins: Spike, ORF3a, and ORF8. Moreover, 36 non-synonymous mutations were identified in the receptor-binding domain (RBD) of the spike protein with a low prevalence (<1%) across all genomes, of which only four could potentially enhance the binding of the SARS-CoV-2 spike protein to the human ACE2 receptor. These results along with intra-genomic divergence of SARS-CoV-2 could indicate that unlike the influenza virus or HIV viruses, SARS-CoV-2 has a low mutation rate which makes the development of an effective global vaccine very likely.
Keywords	covid19
Language	English
Publishing date	2020-10-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens9100829
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Genomic diversity and hotspot mutations in 30,983 SARS-CoV-2 genomes: moving toward a universal vaccine for the "confined virus"?

Alouane, Tarek / Laamarti, Meriem / Essabbar, Abdelomunim / Hakmi, Mohammed / Bouricha, El Mehdi / Chemao-Elfihri, M.W. / Kartti, Souad / Boumajdi, Nasma / Bendani, Houda / Laamarti, Rokaia / Ghrifi, Fatima / Allam, Loubna / Aanniz, Tarik / Ouadghiri, Mouna / El Hafidi, Naima / El Jaoudi, Rachid / Benrahma, Houda / El Attar, Jalil / Mentag, Rachid /

Sbabou, Laila / Nejjari, Chakib / Amzazi, Saaid / Belyamani, Lahcen / Ibrahimi, Azeddine

bioRxiv

Abstract: The Coronavirus disease 19 (COVID-19) pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. To date, the SARS-CoV-2 virus has infected more than 8 million people worldwide and killed over 5% of them. Efforts are being made all ... ...

Abstract	The Coronavirus disease 19 (COVID-19) pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. To date, the SARS-CoV-2 virus has infected more than 8 million people worldwide and killed over 5% of them. Efforts are being made all over the world to control the spread of the disease and most importantly to develop a vaccine. Understanding the genetic evolution of the virus, its geographic characteristics and stability is particularly important for developing a universal vaccine covering all circulating strains of SARS-CoV-2 and for predicting its efficacy. In this perspective, we analyzed the sequences of 30,983 complete genomes from 80 countries located in six geographical zones (Africa, Asia, Europe, North & South America, and Oceania) isolated from December 24, 2019 to May 13, 2020, and compared them to the reference genome. Our in-depth analysis revealed the presence of 3,206 variant sites compared to the reference Wuhan-Hu-1 genome, with a distribution that is largely uniform over all continents. Remarkably, a low frequency of recurrent mutations was observed; only 182 mutations (5.67%) had a prevalence greater than 1%. Nevertheless, fourteen hotspot mutations (> 10%) were identified at different locations, seven at the ORF1ab gene (in regions coding for nsp2, nsp3, nsp6, nsp12, nsp13, nsp14 and nsp15), three in the nucleocapsid protein, one in the spike protein, one in orf3a, and one in orf8. Moreover, 35 non-synonymous mutations were identified in the receptor-binding domain (RBD) of the spike protein with a low prevalence (<1%) across all genomes, of which only four could potentially enhance the binding of the SARS-CoV-2 spike protein to the human receptor ACE2. These results along with the phylogenetic analysis demonstrate that the virus does not have a significant divergence at the protein level compared to the reference both among and within different geographical areas. Unlike the influenza virus or HIV viruses, the slow rate of mutation of SARS-CoV-2 makes the potential of developing an effective global vaccine very likely. Keywords: SARS-CoV-2, genetic evolution, divergence, hotspot mutations, spike protein.
Keywords	covid19
Language	English
Publishing date	2020-06-21
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2020.06.20.163188
Database	COVID19

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Article: Genomic Diversity and Hotspot Mutations in 30,983 SARS-CoV-2 Genomes: Moving Toward a Universal Vaccine for the “Confined Virus”?

Alouane, Tarek / Laamarti, Meriem / Essabbar, Abdelomunim / Hakmi, Mohammed / Bouricha, El Mehdi / Chemao-Elfihri, M. W. / Kartti, Souad / Boumajdi, Nasma / Bendani, Houda / Laamarti, Rokia / Ghrifi, Fatima / Allam, Loubna / Aanniz, Tarik / Ouadghiri, Mouna / El Hafidi, Naima / El Jaoudi, Rachid / Benrahma, Houda / Attar, Jalil El / Mentag, Rachid /

Sbabou, Laila / Nejjari, Chakib / Amzazi, Saaid / Belyamani, Lahcen / Ibrahimi, Azeddine

Pathogens

Abstract: The COVID-19 pandemic has been ongoing since its onset in late November 2019 in Wuhan, China Understanding and monitoring the genetic evolution of the virus, its geographical characteristics, and its stability are particularly important for controlling ... ...

Abstract	The COVID-19 pandemic has been ongoing since its onset in late November 2019 in Wuhan, China Understanding and monitoring the genetic evolution of the virus, its geographical characteristics, and its stability are particularly important for controlling the spread of the disease and especially for the development of a universal vaccine covering all circulating strains From this perspective, we analyzed 30,983 complete SARS-CoV-2 genomes from 79 countries located in the six continents and collected from 24 December 2019, to 13 May 2020, according to the GISAID database Our analysis revealed the presence of 3206 variant sites, with a uniform distribution of mutation types in different geographic areas Remarkably, a low frequency of recurrent mutations has been observed;only 169 mutations (5 27%) had a prevalence greater than 1% of genomes Nevertheless, fourteen non-synonymous hotspot mutations (>10%) have been identified at different locations along the viral genome;eight in ORF1ab polyprotein (in nsp2, nsp3, transmembrane domain, RdRp, helicase, exonuclease, and endoribonuclease), three in nucleocapsid protein, and one in each of three proteins: Spike, ORF3a, and ORF8 Moreover, 36 non-synonymous mutations were identified in the receptor-binding domain (RBD) of the spike protein with a low prevalence (<1%) across all genomes, of which only four could potentially enhance the binding of the SARS-CoV-2 spike protein to the human ACE2 receptor These results along with intra-genomic divergence of SARS-CoV-2 could indicate that unlike the influenza virus or HIV viruses, SARS-CoV-2 has a low mutation rate which makes the development of an effective global vaccine very likely
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #842870
Database	COVID19

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