Sulfated Small Molecules Targeting EBV in Burkitt Lymphoma: From In Silico Screening to the Evidence of In Vitro Effect on Viral Episomal DNA
Epstein–Barr virus (EBV) infects more than 90% of the world population. Following primary infection, Epstein–Barr virus persists in an asymptomatic latent state. Occasionally, it may switch to lytic infection. Latent EBV infection has been associated with several diseases, such as Burkitt lymphoma (...
Gespeichert in:
| Veröffentlicht in: | Chemical biology & drug design 2013-05, Vol.81 (5), p.631-644 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 644 |
|---|---|
| container_issue | 5 |
| container_start_page | 631 |
| container_title | Chemical biology & drug design |
| container_volume | 81 |
| creator | Lima, Raquel T. Seca, Hugo Palmeira, Andreia Fernandes, Miguel X. Castro, Felipe Correia-da-Silva, Marta Nascimento, Maria S. J. Sousa, Emília Pinto, Madalena Vasconcelos, M. Helena |
| description | Epstein–Barr virus (EBV) infects more than 90% of the world population. Following primary infection, Epstein–Barr virus persists in an asymptomatic latent state. Occasionally, it may switch to lytic infection. Latent EBV infection has been associated with several diseases, such as Burkitt lymphoma (BL). To date, there are no available drugs to target latent EBV, and the existing broad‐spectrum antiviral drugs are mainly active against lytic viral infection. Thus, using computational molecular docking, a virtual screen of a library of small molecules, including xanthones and flavonoids (described with potential for antiviral activity against EBV), was carried out targeting EBV proteins. The more interesting molecules were selected for further computational analysis, and sub‐sequently, the compounds were tested in the Raji (BL) cell line, to evaluate their activity against latent EBV. This work identified three novel sulfated small molecules capable of decreasing EBV levels in a BL. Therefore, the in silico screening presents a good approach for the development of new anti‐EBV agents.
The compounds: did not greatly affect cellular viability; decresed EBV DNA load; and reduced LMP1 protein expression. |
| doi_str_mv | 10.1111/cbdd.12109 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_1367485412</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1367485412</sourcerecordid><originalsourceid>FETCH-LOGICAL-i3889-97e646fdeccfbf032893c81a56ee76212560f118e69d4f830fb492519dc877413</originalsourceid><addsrcrecordid>eNqNkcFy0zAQhj0MDC2FCw_A6MjFrWTJksytSZy201CGSShHjSKvWlHZCrIMzUPwzsRNyZm97O7s9_-H_bPsPcGnZFdnZt00p6QguHqRHRPBRI4LWb48zEIcZW_6_gfGjJWFfJ0dFZSWWBB8nP1ZDt7qBA1attp79Dl4MIOHHq10vIPkujtUT26R69BkiA8uJbTYtpv70OpPaB5Di646tHTemYCWJgJ0oyIFlO4B1b9cA50BFOyI3boUA6qtBZNQGPeoPao3rt-5eTS7OX-bvbLa9_DuuZ9k3-b1anqZL75cXE3PF7mjUlZ5JYAzbhswxq4tpoWsqJFElxxA8IIUJceWEAm8apiVFNs1q4qSVI2RQjBCT7KPe99NDD8H6JNqXW_Ae91BGHpFKBdMlowU_4EyTgiXHO_QD8_osG6hUZvoWh236t-3dwDZA7-dh-3hTrAac1RjjuopRzWdzGZP006T7zWuT_B40Oj4oLigolTfby4UnV9_XV1eczWhfwFMPZ1Q</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1346116860</pqid></control><display><type>article</type><title>Sulfated Small Molecules Targeting EBV in Burkitt Lymphoma: From In Silico Screening to the Evidence of In Vitro Effect on Viral Episomal DNA</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Lima, Raquel T. ; Seca, Hugo ; Palmeira, Andreia ; Fernandes, Miguel X. ; Castro, Felipe ; Correia-da-Silva, Marta ; Nascimento, Maria S. J. ; Sousa, Emília ; Pinto, Madalena ; Vasconcelos, M. Helena</creator><creatorcontrib>Lima, Raquel T. ; Seca, Hugo ; Palmeira, Andreia ; Fernandes, Miguel X. ; Castro, Felipe ; Correia-da-Silva, Marta ; Nascimento, Maria S. J. ; Sousa, Emília ; Pinto, Madalena ; Vasconcelos, M. Helena</creatorcontrib><description>Epstein–Barr virus (EBV) infects more than 90% of the world population. Following primary infection, Epstein–Barr virus persists in an asymptomatic latent state. Occasionally, it may switch to lytic infection. Latent EBV infection has been associated with several diseases, such as Burkitt lymphoma (BL). To date, there are no available drugs to target latent EBV, and the existing broad‐spectrum antiviral drugs are mainly active against lytic viral infection. Thus, using computational molecular docking, a virtual screen of a library of small molecules, including xanthones and flavonoids (described with potential for antiviral activity against EBV), was carried out targeting EBV proteins. The more interesting molecules were selected for further computational analysis, and sub‐sequently, the compounds were tested in the Raji (BL) cell line, to evaluate their activity against latent EBV. This work identified three novel sulfated small molecules capable of decreasing EBV levels in a BL. Therefore, the in silico screening presents a good approach for the development of new anti‐EBV agents.
The compounds: did not greatly affect cellular viability; decresed EBV DNA load; and reduced LMP1 protein expression.</description><identifier>ISSN: 1747-0277</identifier><identifier>EISSN: 1747-0285</identifier><identifier>DOI: 10.1111/cbdd.12109</identifier><identifier>PMID: 23350710</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Antiviral Agents - chemical synthesis ; Antiviral Agents - chemistry ; Antiviral Agents - pharmacology ; antivirals ; Burkitt lymphoma ; Burkitt Lymphoma - drug therapy ; Burkitt Lymphoma - virology ; Cell Line, Tumor ; DNA, Neoplasm - antagonists & inhibitors ; DNA, Neoplasm - chemistry ; DNA, Neoplasm - metabolism ; DNA, Viral - antagonists & inhibitors ; DNA, Viral - chemistry ; DNA, Viral - metabolism ; Drug Delivery Systems ; Drug Discovery ; Drug Screening Assays, Antitumor ; Epstein-Barr virus ; Flavonoids - chemical synthesis ; Flavonoids - chemistry ; Flavonoids - pharmacology ; Herpesvirus 4, Human - physiology ; Humans ; Plasmids - antagonists & inhibitors ; Plasmids - chemistry ; Plasmids - metabolism ; sulfated small molecules ; virtual screening ; Virus Latency - drug effects ; Xanthones - chemical synthesis ; Xanthones - chemistry ; Xanthones - pharmacology</subject><ispartof>Chemical biology & drug design, 2013-05, Vol.81 (5), p.631-644</ispartof><rights>2013 John Wiley & Sons A/S</rights><rights>2013 John Wiley & Sons A/S.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fcbdd.12109$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fcbdd.12109$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23350710$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lima, Raquel T.</creatorcontrib><creatorcontrib>Seca, Hugo</creatorcontrib><creatorcontrib>Palmeira, Andreia</creatorcontrib><creatorcontrib>Fernandes, Miguel X.</creatorcontrib><creatorcontrib>Castro, Felipe</creatorcontrib><creatorcontrib>Correia-da-Silva, Marta</creatorcontrib><creatorcontrib>Nascimento, Maria S. J.</creatorcontrib><creatorcontrib>Sousa, Emília</creatorcontrib><creatorcontrib>Pinto, Madalena</creatorcontrib><creatorcontrib>Vasconcelos, M. Helena</creatorcontrib><title>Sulfated Small Molecules Targeting EBV in Burkitt Lymphoma: From In Silico Screening to the Evidence of In Vitro Effect on Viral Episomal DNA</title><title>Chemical biology & drug design</title><addtitle>Chem Biol Drug Des</addtitle><description>Epstein–Barr virus (EBV) infects more than 90% of the world population. Following primary infection, Epstein–Barr virus persists in an asymptomatic latent state. Occasionally, it may switch to lytic infection. Latent EBV infection has been associated with several diseases, such as Burkitt lymphoma (BL). To date, there are no available drugs to target latent EBV, and the existing broad‐spectrum antiviral drugs are mainly active against lytic viral infection. Thus, using computational molecular docking, a virtual screen of a library of small molecules, including xanthones and flavonoids (described with potential for antiviral activity against EBV), was carried out targeting EBV proteins. The more interesting molecules were selected for further computational analysis, and sub‐sequently, the compounds were tested in the Raji (BL) cell line, to evaluate their activity against latent EBV. This work identified three novel sulfated small molecules capable of decreasing EBV levels in a BL. Therefore, the in silico screening presents a good approach for the development of new anti‐EBV agents.
The compounds: did not greatly affect cellular viability; decresed EBV DNA load; and reduced LMP1 protein expression.</description><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antiviral Agents - chemical synthesis</subject><subject>Antiviral Agents - chemistry</subject><subject>Antiviral Agents - pharmacology</subject><subject>antivirals</subject><subject>Burkitt lymphoma</subject><subject>Burkitt Lymphoma - drug therapy</subject><subject>Burkitt Lymphoma - virology</subject><subject>Cell Line, Tumor</subject><subject>DNA, Neoplasm - antagonists & inhibitors</subject><subject>DNA, Neoplasm - chemistry</subject><subject>DNA, Neoplasm - metabolism</subject><subject>DNA, Viral - antagonists & inhibitors</subject><subject>DNA, Viral - chemistry</subject><subject>DNA, Viral - metabolism</subject><subject>Drug Delivery Systems</subject><subject>Drug Discovery</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Epstein-Barr virus</subject><subject>Flavonoids - chemical synthesis</subject><subject>Flavonoids - chemistry</subject><subject>Flavonoids - pharmacology</subject><subject>Herpesvirus 4, Human - physiology</subject><subject>Humans</subject><subject>Plasmids - antagonists & inhibitors</subject><subject>Plasmids - chemistry</subject><subject>Plasmids - metabolism</subject><subject>sulfated small molecules</subject><subject>virtual screening</subject><subject>Virus Latency - drug effects</subject><subject>Xanthones - chemical synthesis</subject><subject>Xanthones - chemistry</subject><subject>Xanthones - pharmacology</subject><issn>1747-0277</issn><issn>1747-0285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcFy0zAQhj0MDC2FCw_A6MjFrWTJksytSZy201CGSShHjSKvWlHZCrIMzUPwzsRNyZm97O7s9_-H_bPsPcGnZFdnZt00p6QguHqRHRPBRI4LWb48zEIcZW_6_gfGjJWFfJ0dFZSWWBB8nP1ZDt7qBA1attp79Dl4MIOHHq10vIPkujtUT26R69BkiA8uJbTYtpv70OpPaB5Di646tHTemYCWJgJ0oyIFlO4B1b9cA50BFOyI3boUA6qtBZNQGPeoPao3rt-5eTS7OX-bvbLa9_DuuZ9k3-b1anqZL75cXE3PF7mjUlZ5JYAzbhswxq4tpoWsqJFElxxA8IIUJceWEAm8apiVFNs1q4qSVI2RQjBCT7KPe99NDD8H6JNqXW_Ae91BGHpFKBdMlowU_4EyTgiXHO_QD8_osG6hUZvoWh236t-3dwDZA7-dh-3hTrAac1RjjuopRzWdzGZP006T7zWuT_B40Oj4oLigolTfby4UnV9_XV1eczWhfwFMPZ1Q</recordid><startdate>201305</startdate><enddate>201305</enddate><creator>Lima, Raquel T.</creator><creator>Seca, Hugo</creator><creator>Palmeira, Andreia</creator><creator>Fernandes, Miguel X.</creator><creator>Castro, Felipe</creator><creator>Correia-da-Silva, Marta</creator><creator>Nascimento, Maria S. J.</creator><creator>Sousa, Emília</creator><creator>Pinto, Madalena</creator><creator>Vasconcelos, M. Helena</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>7TM</scope><scope>7U9</scope><scope>H94</scope></search><sort><creationdate>201305</creationdate><title>Sulfated Small Molecules Targeting EBV in Burkitt Lymphoma: From In Silico Screening to the Evidence of In Vitro Effect on Viral Episomal DNA</title><author>Lima, Raquel T. ; Seca, Hugo ; Palmeira, Andreia ; Fernandes, Miguel X. ; Castro, Felipe ; Correia-da-Silva, Marta ; Nascimento, Maria S. J. ; Sousa, Emília ; Pinto, Madalena ; Vasconcelos, M. Helena</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-i3889-97e646fdeccfbf032893c81a56ee76212560f118e69d4f830fb492519dc877413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antiviral Agents - chemical synthesis</topic><topic>Antiviral Agents - chemistry</topic><topic>Antiviral Agents - pharmacology</topic><topic>antivirals</topic><topic>Burkitt lymphoma</topic><topic>Burkitt Lymphoma - drug therapy</topic><topic>Burkitt Lymphoma - virology</topic><topic>Cell Line, Tumor</topic><topic>DNA, Neoplasm - antagonists & inhibitors</topic><topic>DNA, Neoplasm - chemistry</topic><topic>DNA, Neoplasm - metabolism</topic><topic>DNA, Viral - antagonists & inhibitors</topic><topic>DNA, Viral - chemistry</topic><topic>DNA, Viral - metabolism</topic><topic>Drug Delivery Systems</topic><topic>Drug Discovery</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Epstein-Barr virus</topic><topic>Flavonoids - chemical synthesis</topic><topic>Flavonoids - chemistry</topic><topic>Flavonoids - pharmacology</topic><topic>Herpesvirus 4, Human - physiology</topic><topic>Humans</topic><topic>Plasmids - antagonists & inhibitors</topic><topic>Plasmids - chemistry</topic><topic>Plasmids - metabolism</topic><topic>sulfated small molecules</topic><topic>virtual screening</topic><topic>Virus Latency - drug effects</topic><topic>Xanthones - chemical synthesis</topic><topic>Xanthones - chemistry</topic><topic>Xanthones - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lima, Raquel T.</creatorcontrib><creatorcontrib>Seca, Hugo</creatorcontrib><creatorcontrib>Palmeira, Andreia</creatorcontrib><creatorcontrib>Fernandes, Miguel X.</creatorcontrib><creatorcontrib>Castro, Felipe</creatorcontrib><creatorcontrib>Correia-da-Silva, Marta</creatorcontrib><creatorcontrib>Nascimento, Maria S. J.</creatorcontrib><creatorcontrib>Sousa, Emília</creatorcontrib><creatorcontrib>Pinto, Madalena</creatorcontrib><creatorcontrib>Vasconcelos, M. Helena</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Chemical biology & drug design</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lima, Raquel T.</au><au>Seca, Hugo</au><au>Palmeira, Andreia</au><au>Fernandes, Miguel X.</au><au>Castro, Felipe</au><au>Correia-da-Silva, Marta</au><au>Nascimento, Maria S. J.</au><au>Sousa, Emília</au><au>Pinto, Madalena</au><au>Vasconcelos, M. Helena</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sulfated Small Molecules Targeting EBV in Burkitt Lymphoma: From In Silico Screening to the Evidence of In Vitro Effect on Viral Episomal DNA</atitle><jtitle>Chemical biology & drug design</jtitle><addtitle>Chem Biol Drug Des</addtitle><date>2013-05</date><risdate>2013</risdate><volume>81</volume><issue>5</issue><spage>631</spage><epage>644</epage><pages>631-644</pages><issn>1747-0277</issn><eissn>1747-0285</eissn><abstract>Epstein–Barr virus (EBV) infects more than 90% of the world population. Following primary infection, Epstein–Barr virus persists in an asymptomatic latent state. Occasionally, it may switch to lytic infection. Latent EBV infection has been associated with several diseases, such as Burkitt lymphoma (BL). To date, there are no available drugs to target latent EBV, and the existing broad‐spectrum antiviral drugs are mainly active against lytic viral infection. Thus, using computational molecular docking, a virtual screen of a library of small molecules, including xanthones and flavonoids (described with potential for antiviral activity against EBV), was carried out targeting EBV proteins. The more interesting molecules were selected for further computational analysis, and sub‐sequently, the compounds were tested in the Raji (BL) cell line, to evaluate their activity against latent EBV. This work identified three novel sulfated small molecules capable of decreasing EBV levels in a BL. Therefore, the in silico screening presents a good approach for the development of new anti‐EBV agents.
The compounds: did not greatly affect cellular viability; decresed EBV DNA load; and reduced LMP1 protein expression.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>23350710</pmid><doi>10.1111/cbdd.12109</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1747-0277 |
| ispartof | Chemical biology & drug design, 2013-05, Vol.81 (5), p.631-644 |
| issn | 1747-0277 1747-0285 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1367485412 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Antiviral Agents - chemical synthesis Antiviral Agents - chemistry Antiviral Agents - pharmacology antivirals Burkitt lymphoma Burkitt Lymphoma - drug therapy Burkitt Lymphoma - virology Cell Line, Tumor DNA, Neoplasm - antagonists & inhibitors DNA, Neoplasm - chemistry DNA, Neoplasm - metabolism DNA, Viral - antagonists & inhibitors DNA, Viral - chemistry DNA, Viral - metabolism Drug Delivery Systems Drug Discovery Drug Screening Assays, Antitumor Epstein-Barr virus Flavonoids - chemical synthesis Flavonoids - chemistry Flavonoids - pharmacology Herpesvirus 4, Human - physiology Humans Plasmids - antagonists & inhibitors Plasmids - chemistry Plasmids - metabolism sulfated small molecules virtual screening Virus Latency - drug effects Xanthones - chemical synthesis Xanthones - chemistry Xanthones - pharmacology |
| title | Sulfated Small Molecules Targeting EBV in Burkitt Lymphoma: From In Silico Screening to the Evidence of In Vitro Effect on Viral Episomal DNA |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T10%3A35%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Sulfated%20Small%20Molecules%20Targeting%20EBV%20in%20Burkitt%20Lymphoma:%20From%20In%20Silico%20Screening%20to%20the%20Evidence%20of%20In%20Vitro%20Effect%20on%20Viral%20Episomal%20DNA&rft.jtitle=Chemical%20biology%20&%20drug%20design&rft.au=Lima,%20Raquel%20T.&rft.date=2013-05&rft.volume=81&rft.issue=5&rft.spage=631&rft.epage=644&rft.pages=631-644&rft.issn=1747-0277&rft.eissn=1747-0285&rft_id=info:doi/10.1111/cbdd.12109&rft_dat=%3Cproquest_pubme%3E1367485412%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1346116860&rft_id=info:pmid/23350710&rfr_iscdi=true |