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Functional variation (Q63R) in the cannabinoid CB2 receptor may affect the severity of COVID-19: a human study and molecular docking
Evidence supports a role of host genetic diversity in the clinical course of coronavirus disease 2019 (COVID-19). Variation in the cannabinoid CB2 receptor gene ( CNR2 ) could affect the regulatory action of endocannabinoids on the immune system, resulting in an increased risk of various inflammator...
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| Published in: | Archives of virology 2021-11, Vol.166 (11), p.3117-3126 |
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| container_title | Archives of virology |
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| creator | Rastegar, Mostafa Samadizadeh, Saeed Yasaghi, Mohammad Moradi, Abdolvahab Tabarraei, Alijan Salimi, Vahid Tahamtan, Alireza |
| description | Evidence supports a role of host genetic diversity in the clinical course of coronavirus disease 2019 (COVID-19). Variation in the cannabinoid CB2 receptor gene (
CNR2
) could affect the regulatory action of endocannabinoids on the immune system, resulting in an increased risk of various inflammatory diseases. The present study investigated the relationship between the
CNR2
-Q63R variant and COVID-19 severity. A total of 200 Iranian COVID-19 patients were enrolled in the study and genotyped using a TaqMan assay. The co-dominant, dominant, recessive, over-dominant, and additive inheritance models were analyzed using SNPStats software.
In silico
molecular docking was also performed to simulate the effects of the Q63R variation on CB2 binding with a ligand and with the G-protein. A significant difference in the Q63R allele and genotype distribution was found between expired and discharged COVID-19 patients in co-dominant, recessive, and additive inheritance models. The molecular docking results showed that the predicted structure of mutant CB2 (63R type) could not bind to the G-protein in the correct position. The data indicated that the Q63R variation in the
CNR2
gene may affect the severity of COVID-19. Identification of genes related to susceptibility and severity of COVID-19 may lead to specific targets for drug repurposing or development.
Graphic abstract |
| doi_str_mv | 10.1007/s00705-021-05223-7 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8435402</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2572213749</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-f6faecff48a4097c1a7b0ab8ff2398c33224eaa355e84bd269849c2f9950131c3</originalsourceid><addsrcrecordid>eNp9kU2PFCEQhonRuOPqH_BgSLysh1a-uhs8mOjo6iabbDTqlVTTMMPaDSN0TzJ3f7jMzLp-HEwIVKinXqh6EXpMyXNKSPsil43UFWG0IjVjvGrvoAUVnFWyVfIuWhBORCUbIk_Qg5yvCSkXvL6PTrioaVlqgX6cz8FMPgYY8BaSh32Mzz42_NMz7AOe1hYbCAE6H6Lv8fINw8kau5liwiPsMDhnzXTgst3a5Kcdjg4vr75evK2oeokBr-cRAs7T3Bc89HiMgzXzAAn30XzzYfUQ3XMwZPvo5jxFX87ffV5-qC6v3l8sX19WRrRiqlzjwBrnhARBVGsotB2BTjrHuJKGc8aEBeB1baXoetYoKZRhTqmaUE4NP0WvjrqbuRttb2yYEgx6k_wIaacjeP13Jvi1XsWtloLXgrAicHYjkOL32eZJjz4bOwwQbJyzZnXLGOWtUAV9-g96HedUxnyglCxgs6fYkTIp5pysu_0MJXpvsj6arIvJ-mCybkvRkz_buC355WoB-BHIJRVWNv1--z-yPwEFwrIr</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2579872269</pqid></control><display><type>article</type><title>Functional variation (Q63R) in the cannabinoid CB2 receptor may affect the severity of COVID-19: a human study and molecular docking</title><source>Springer Link</source><creator>Rastegar, Mostafa ; Samadizadeh, Saeed ; Yasaghi, Mohammad ; Moradi, Abdolvahab ; Tabarraei, Alijan ; Salimi, Vahid ; Tahamtan, Alireza</creator><creatorcontrib>Rastegar, Mostafa ; Samadizadeh, Saeed ; Yasaghi, Mohammad ; Moradi, Abdolvahab ; Tabarraei, Alijan ; Salimi, Vahid ; Tahamtan, Alireza</creatorcontrib><description>Evidence supports a role of host genetic diversity in the clinical course of coronavirus disease 2019 (COVID-19). Variation in the cannabinoid CB2 receptor gene (
CNR2
) could affect the regulatory action of endocannabinoids on the immune system, resulting in an increased risk of various inflammatory diseases. The present study investigated the relationship between the
CNR2
-Q63R variant and COVID-19 severity. A total of 200 Iranian COVID-19 patients were enrolled in the study and genotyped using a TaqMan assay. The co-dominant, dominant, recessive, over-dominant, and additive inheritance models were analyzed using SNPStats software.
In silico
molecular docking was also performed to simulate the effects of the Q63R variation on CB2 binding with a ligand and with the G-protein. A significant difference in the Q63R allele and genotype distribution was found between expired and discharged COVID-19 patients in co-dominant, recessive, and additive inheritance models. The molecular docking results showed that the predicted structure of mutant CB2 (63R type) could not bind to the G-protein in the correct position. The data indicated that the Q63R variation in the
CNR2
gene may affect the severity of COVID-19. Identification of genes related to susceptibility and severity of COVID-19 may lead to specific targets for drug repurposing or development.
Graphic abstract</description><identifier>ISSN: 0304-8608</identifier><identifier>ISSN: 1432-8798</identifier><identifier>EISSN: 1432-8798</identifier><identifier>DOI: 10.1007/s00705-021-05223-7</identifier><identifier>PMID: 34514519</identifier><language>eng</language><publisher>Vienna: Springer Vienna</publisher><subject>Biomedical and Life Sciences ; Biomedicine ; Cannabinoid CB2 receptors ; Case-Control Studies ; Coronaviruses ; COVID-19 ; COVID-19 - diagnosis ; COVID-19 - genetics ; Female ; Gene Frequency ; Genetic diversity ; Genetic Predisposition to Disease - genetics ; Genotype ; Genotypes ; GTP-Binding Proteins - metabolism ; Heredity ; Humans ; Immune system ; Infectious Diseases ; Inflammatory diseases ; Iran ; Male ; Medical Microbiology ; Middle Aged ; Models, Molecular ; Molecular Docking Simulation ; Molecular modelling ; Original ; Original Article ; Patients ; Polymorphism, Genetic ; Protein Binding ; Receptor, Cannabinoid, CB2 - chemistry ; Receptor, Cannabinoid, CB2 - genetics ; Receptor, Cannabinoid, CB2 - metabolism ; SARS-CoV-2 ; Severity of Illness Index ; Virology</subject><ispartof>Archives of virology, 2021-11, Vol.166 (11), p.3117-3126</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-f6faecff48a4097c1a7b0ab8ff2398c33224eaa355e84bd269849c2f9950131c3</citedby><cites>FETCH-LOGICAL-c474t-f6faecff48a4097c1a7b0ab8ff2398c33224eaa355e84bd269849c2f9950131c3</cites><orcidid>0000-0001-7680-5698</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34514519$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rastegar, Mostafa</creatorcontrib><creatorcontrib>Samadizadeh, Saeed</creatorcontrib><creatorcontrib>Yasaghi, Mohammad</creatorcontrib><creatorcontrib>Moradi, Abdolvahab</creatorcontrib><creatorcontrib>Tabarraei, Alijan</creatorcontrib><creatorcontrib>Salimi, Vahid</creatorcontrib><creatorcontrib>Tahamtan, Alireza</creatorcontrib><title>Functional variation (Q63R) in the cannabinoid CB2 receptor may affect the severity of COVID-19: a human study and molecular docking</title><title>Archives of virology</title><addtitle>Arch Virol</addtitle><addtitle>Arch Virol</addtitle><description>Evidence supports a role of host genetic diversity in the clinical course of coronavirus disease 2019 (COVID-19). Variation in the cannabinoid CB2 receptor gene (
CNR2
) could affect the regulatory action of endocannabinoids on the immune system, resulting in an increased risk of various inflammatory diseases. The present study investigated the relationship between the
CNR2
-Q63R variant and COVID-19 severity. A total of 200 Iranian COVID-19 patients were enrolled in the study and genotyped using a TaqMan assay. The co-dominant, dominant, recessive, over-dominant, and additive inheritance models were analyzed using SNPStats software.
In silico
molecular docking was also performed to simulate the effects of the Q63R variation on CB2 binding with a ligand and with the G-protein. A significant difference in the Q63R allele and genotype distribution was found between expired and discharged COVID-19 patients in co-dominant, recessive, and additive inheritance models. The molecular docking results showed that the predicted structure of mutant CB2 (63R type) could not bind to the G-protein in the correct position. The data indicated that the Q63R variation in the
CNR2
gene may affect the severity of COVID-19. Identification of genes related to susceptibility and severity of COVID-19 may lead to specific targets for drug repurposing or development.
Graphic abstract</description><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cannabinoid CB2 receptors</subject><subject>Case-Control Studies</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>COVID-19 - diagnosis</subject><subject>COVID-19 - genetics</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genotype</subject><subject>Genotypes</subject><subject>GTP-Binding Proteins - metabolism</subject><subject>Heredity</subject><subject>Humans</subject><subject>Immune system</subject><subject>Infectious Diseases</subject><subject>Inflammatory diseases</subject><subject>Iran</subject><subject>Male</subject><subject>Medical Microbiology</subject><subject>Middle Aged</subject><subject>Models, Molecular</subject><subject>Molecular Docking Simulation</subject><subject>Molecular modelling</subject><subject>Original</subject><subject>Original Article</subject><subject>Patients</subject><subject>Polymorphism, Genetic</subject><subject>Protein Binding</subject><subject>Receptor, Cannabinoid, CB2 - chemistry</subject><subject>Receptor, Cannabinoid, CB2 - genetics</subject><subject>Receptor, Cannabinoid, CB2 - metabolism</subject><subject>SARS-CoV-2</subject><subject>Severity of Illness Index</subject><subject>Virology</subject><issn>0304-8608</issn><issn>1432-8798</issn><issn>1432-8798</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kU2PFCEQhonRuOPqH_BgSLysh1a-uhs8mOjo6iabbDTqlVTTMMPaDSN0TzJ3f7jMzLp-HEwIVKinXqh6EXpMyXNKSPsil43UFWG0IjVjvGrvoAUVnFWyVfIuWhBORCUbIk_Qg5yvCSkXvL6PTrioaVlqgX6cz8FMPgYY8BaSh32Mzz42_NMz7AOe1hYbCAE6H6Lv8fINw8kau5liwiPsMDhnzXTgst3a5Kcdjg4vr75evK2oeokBr-cRAs7T3Bc89HiMgzXzAAn30XzzYfUQ3XMwZPvo5jxFX87ffV5-qC6v3l8sX19WRrRiqlzjwBrnhARBVGsotB2BTjrHuJKGc8aEBeB1baXoetYoKZRhTqmaUE4NP0WvjrqbuRttb2yYEgx6k_wIaacjeP13Jvi1XsWtloLXgrAicHYjkOL32eZJjz4bOwwQbJyzZnXLGOWtUAV9-g96HedUxnyglCxgs6fYkTIp5pysu_0MJXpvsj6arIvJ-mCybkvRkz_buC355WoB-BHIJRVWNv1--z-yPwEFwrIr</recordid><startdate>20211101</startdate><enddate>20211101</enddate><creator>Rastegar, Mostafa</creator><creator>Samadizadeh, Saeed</creator><creator>Yasaghi, Mohammad</creator><creator>Moradi, Abdolvahab</creator><creator>Tabarraei, Alijan</creator><creator>Salimi, Vahid</creator><creator>Tahamtan, Alireza</creator><general>Springer Vienna</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7680-5698</orcidid></search><sort><creationdate>20211101</creationdate><title>Functional variation (Q63R) in the cannabinoid CB2 receptor may affect the severity of COVID-19: a human study and molecular docking</title><author>Rastegar, Mostafa ; Samadizadeh, Saeed ; Yasaghi, Mohammad ; Moradi, Abdolvahab ; Tabarraei, Alijan ; Salimi, Vahid ; Tahamtan, Alireza</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-f6faecff48a4097c1a7b0ab8ff2398c33224eaa355e84bd269849c2f9950131c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cannabinoid CB2 receptors</topic><topic>Case-Control Studies</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>COVID-19 - diagnosis</topic><topic>COVID-19 - genetics</topic><topic>Female</topic><topic>Gene Frequency</topic><topic>Genetic diversity</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genotype</topic><topic>Genotypes</topic><topic>GTP-Binding Proteins - metabolism</topic><topic>Heredity</topic><topic>Humans</topic><topic>Immune system</topic><topic>Infectious Diseases</topic><topic>Inflammatory diseases</topic><topic>Iran</topic><topic>Male</topic><topic>Medical Microbiology</topic><topic>Middle Aged</topic><topic>Models, Molecular</topic><topic>Molecular Docking Simulation</topic><topic>Molecular modelling</topic><topic>Original</topic><topic>Original Article</topic><topic>Patients</topic><topic>Polymorphism, Genetic</topic><topic>Protein Binding</topic><topic>Receptor, Cannabinoid, CB2 - chemistry</topic><topic>Receptor, Cannabinoid, CB2 - genetics</topic><topic>Receptor, Cannabinoid, CB2 - metabolism</topic><topic>SARS-CoV-2</topic><topic>Severity of Illness Index</topic><topic>Virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rastegar, Mostafa</creatorcontrib><creatorcontrib>Samadizadeh, Saeed</creatorcontrib><creatorcontrib>Yasaghi, Mohammad</creatorcontrib><creatorcontrib>Moradi, Abdolvahab</creatorcontrib><creatorcontrib>Tabarraei, Alijan</creatorcontrib><creatorcontrib>Salimi, Vahid</creatorcontrib><creatorcontrib>Tahamtan, Alireza</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Biological Science Journals</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Archives of virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rastegar, Mostafa</au><au>Samadizadeh, Saeed</au><au>Yasaghi, Mohammad</au><au>Moradi, Abdolvahab</au><au>Tabarraei, Alijan</au><au>Salimi, Vahid</au><au>Tahamtan, Alireza</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional variation (Q63R) in the cannabinoid CB2 receptor may affect the severity of COVID-19: a human study and molecular docking</atitle><jtitle>Archives of virology</jtitle><stitle>Arch Virol</stitle><addtitle>Arch Virol</addtitle><date>2021-11-01</date><risdate>2021</risdate><volume>166</volume><issue>11</issue><spage>3117</spage><epage>3126</epage><pages>3117-3126</pages><issn>0304-8608</issn><issn>1432-8798</issn><eissn>1432-8798</eissn><abstract>Evidence supports a role of host genetic diversity in the clinical course of coronavirus disease 2019 (COVID-19). Variation in the cannabinoid CB2 receptor gene (
CNR2
) could affect the regulatory action of endocannabinoids on the immune system, resulting in an increased risk of various inflammatory diseases. The present study investigated the relationship between the
CNR2
-Q63R variant and COVID-19 severity. A total of 200 Iranian COVID-19 patients were enrolled in the study and genotyped using a TaqMan assay. The co-dominant, dominant, recessive, over-dominant, and additive inheritance models were analyzed using SNPStats software.
In silico
molecular docking was also performed to simulate the effects of the Q63R variation on CB2 binding with a ligand and with the G-protein. A significant difference in the Q63R allele and genotype distribution was found between expired and discharged COVID-19 patients in co-dominant, recessive, and additive inheritance models. The molecular docking results showed that the predicted structure of mutant CB2 (63R type) could not bind to the G-protein in the correct position. The data indicated that the Q63R variation in the
CNR2
gene may affect the severity of COVID-19. Identification of genes related to susceptibility and severity of COVID-19 may lead to specific targets for drug repurposing or development.
Graphic abstract</abstract><cop>Vienna</cop><pub>Springer Vienna</pub><pmid>34514519</pmid><doi>10.1007/s00705-021-05223-7</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-7680-5698</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Archives of virology, 2021-11, Vol.166 (11), p.3117-3126 |
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| language | eng |
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| subjects | Biomedical and Life Sciences Biomedicine Cannabinoid CB2 receptors Case-Control Studies Coronaviruses COVID-19 COVID-19 - diagnosis COVID-19 - genetics Female Gene Frequency Genetic diversity Genetic Predisposition to Disease - genetics Genotype Genotypes GTP-Binding Proteins - metabolism Heredity Humans Immune system Infectious Diseases Inflammatory diseases Iran Male Medical Microbiology Middle Aged Models, Molecular Molecular Docking Simulation Molecular modelling Original Original Article Patients Polymorphism, Genetic Protein Binding Receptor, Cannabinoid, CB2 - chemistry Receptor, Cannabinoid, CB2 - genetics Receptor, Cannabinoid, CB2 - metabolism SARS-CoV-2 Severity of Illness Index Virology |
| title | Functional variation (Q63R) in the cannabinoid CB2 receptor may affect the severity of COVID-19: a human study and molecular docking |
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