Buckyballs to fight pandemic: Water-soluble fullerene derivatives with pendant carboxylic groups emerge as a new family of promising SARS-CoV-2 inhibitors
[Display omitted] •Individual water-soluble fullerene derivatives were shown to inhibit SARS-CoV-2.•High selectivity indexes up to 214 were achieved for leading compounds.•Time-of-addition test revealed spike protein and main protease as probable targets. Herein, we present the first experimental st...
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| Veröffentlicht in: | Bioorganic chemistry 2025-01, Vol.154, p.108097, Article 108097 |
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| container_title | Bioorganic chemistry |
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| creator | Kraevaya, Olga A. Bolshakova, Valeriya S. Slita, Alexander V. Esaulkova, Iana L. Zhilenkov, Alexander V. Mikhalsky, Mikhail G. Sinegubova, Ekaterina O. Voronov, Ilya I. Peregudov, Alexander S. Shestakov, Alexander F. Zarubaev, Vladimir V. Troshin, Pavel A. |
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•Individual water-soluble fullerene derivatives were shown to inhibit SARS-CoV-2.•High selectivity indexes up to 214 were achieved for leading compounds.•Time-of-addition test revealed spike protein and main protease as probable targets.
Herein, we present the first experimental study of individual water-soluble fullerene derivatives proving their ability to inhibit SARS-CoV-2 in vitro. The initial screening allowed us to identify a few new compounds that have demonstrated pronounced antiviral activity with IC50 values as low as 390 nM and selectivity indexes reaching 214. Time-of-addition analysis and molecular docking results suggested that the viral protease and/or the spike protein are the most probable targets inhibited by the fullerene derivatives. Further rational design of fullerene derivatives might lead to the development of compounds with further enhanced antiviral activity and decreased toxicity. |
| doi_str_mv | 10.1016/j.bioorg.2024.108097 |
| format | Article |
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•Individual water-soluble fullerene derivatives were shown to inhibit SARS-CoV-2.•High selectivity indexes up to 214 were achieved for leading compounds.•Time-of-addition test revealed spike protein and main protease as probable targets.
Herein, we present the first experimental study of individual water-soluble fullerene derivatives proving their ability to inhibit SARS-CoV-2 in vitro. The initial screening allowed us to identify a few new compounds that have demonstrated pronounced antiviral activity with IC50 values as low as 390 nM and selectivity indexes reaching 214. Time-of-addition analysis and molecular docking results suggested that the viral protease and/or the spike protein are the most probable targets inhibited by the fullerene derivatives. Further rational design of fullerene derivatives might lead to the development of compounds with further enhanced antiviral activity and decreased toxicity.</description><identifier>ISSN: 0045-2068</identifier><identifier>ISSN: 1090-2120</identifier><identifier>EISSN: 1090-2120</identifier><identifier>DOI: 10.1016/j.bioorg.2024.108097</identifier><identifier>PMID: 39729769</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Antiviral activity ; Antiviral Agents - chemical synthesis ; Antiviral Agents - chemistry ; Antiviral Agents - pharmacology ; Carboxylic Acids - chemical synthesis ; Carboxylic Acids - chemistry ; Carboxylic Acids - pharmacology ; Coronavirus 3C Proteases - antagonists & inhibitors ; Coronavirus 3C Proteases - metabolism ; COVID-19 - epidemiology ; COVID-19 - virology ; COVID-19 Drug Treatment ; Dose-Response Relationship, Drug ; Fullerene derivatives ; Fullerenes - chemistry ; Fullerenes - pharmacology ; Humans ; Mechanism ; Microbial Sensitivity Tests ; Molecular Docking Simulation ; Molecular Structure ; SARS-CoV-2 ; SARS-CoV-2 - drug effects ; Solubility ; Spike Glycoprotein, Coronavirus - antagonists & inhibitors ; Spike Glycoprotein, Coronavirus - chemistry ; Spike Glycoprotein, Coronavirus - metabolism ; Structure-Activity Relationship ; Water - chemistry</subject><ispartof>Bioorganic chemistry, 2025-01, Vol.154, p.108097, Article 108097</ispartof><rights>2024 Elsevier Inc.</rights><rights>Copyright © 2024 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c1569-f31da198ffa5466478cdcf063f1cd2263477cd05a5fc93775aed1bb3bcf097ab3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0045206824010022$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39729769$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kraevaya, Olga A.</creatorcontrib><creatorcontrib>Bolshakova, Valeriya S.</creatorcontrib><creatorcontrib>Slita, Alexander V.</creatorcontrib><creatorcontrib>Esaulkova, Iana L.</creatorcontrib><creatorcontrib>Zhilenkov, Alexander V.</creatorcontrib><creatorcontrib>Mikhalsky, Mikhail G.</creatorcontrib><creatorcontrib>Sinegubova, Ekaterina O.</creatorcontrib><creatorcontrib>Voronov, Ilya I.</creatorcontrib><creatorcontrib>Peregudov, Alexander S.</creatorcontrib><creatorcontrib>Shestakov, Alexander F.</creatorcontrib><creatorcontrib>Zarubaev, Vladimir V.</creatorcontrib><creatorcontrib>Troshin, Pavel A.</creatorcontrib><title>Buckyballs to fight pandemic: Water-soluble fullerene derivatives with pendant carboxylic groups emerge as a new family of promising SARS-CoV-2 inhibitors</title><title>Bioorganic chemistry</title><addtitle>Bioorg Chem</addtitle><description>[Display omitted]
•Individual water-soluble fullerene derivatives were shown to inhibit SARS-CoV-2.•High selectivity indexes up to 214 were achieved for leading compounds.•Time-of-addition test revealed spike protein and main protease as probable targets.
Herein, we present the first experimental study of individual water-soluble fullerene derivatives proving their ability to inhibit SARS-CoV-2 in vitro. The initial screening allowed us to identify a few new compounds that have demonstrated pronounced antiviral activity with IC50 values as low as 390 nM and selectivity indexes reaching 214. Time-of-addition analysis and molecular docking results suggested that the viral protease and/or the spike protein are the most probable targets inhibited by the fullerene derivatives. Further rational design of fullerene derivatives might lead to the development of compounds with further enhanced antiviral activity and decreased toxicity.</description><subject>Antiviral activity</subject><subject>Antiviral Agents - chemical synthesis</subject><subject>Antiviral Agents - chemistry</subject><subject>Antiviral Agents - pharmacology</subject><subject>Carboxylic Acids - chemical synthesis</subject><subject>Carboxylic Acids - chemistry</subject><subject>Carboxylic Acids - pharmacology</subject><subject>Coronavirus 3C Proteases - antagonists & inhibitors</subject><subject>Coronavirus 3C Proteases - metabolism</subject><subject>COVID-19 - epidemiology</subject><subject>COVID-19 - virology</subject><subject>COVID-19 Drug Treatment</subject><subject>Dose-Response Relationship, Drug</subject><subject>Fullerene derivatives</subject><subject>Fullerenes - chemistry</subject><subject>Fullerenes - pharmacology</subject><subject>Humans</subject><subject>Mechanism</subject><subject>Microbial Sensitivity Tests</subject><subject>Molecular Docking Simulation</subject><subject>Molecular Structure</subject><subject>SARS-CoV-2</subject><subject>SARS-CoV-2 - drug effects</subject><subject>Solubility</subject><subject>Spike Glycoprotein, Coronavirus - antagonists & inhibitors</subject><subject>Spike Glycoprotein, Coronavirus - chemistry</subject><subject>Spike Glycoprotein, Coronavirus - metabolism</subject><subject>Structure-Activity Relationship</subject><subject>Water - chemistry</subject><issn>0045-2068</issn><issn>1090-2120</issn><issn>1090-2120</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcluFDEQhi0EIpPAGyBURy492L15zAEpjCAgRUIiLEfLS7nHg7s9sbsnzKvwtHTUgSOnkkrfX4s-Ql4wumaUta_3a-1jTN26pGU9tzZU8EdkxaigRclK-pisKK2boqTt5oyc57ynlLGat0_JWSV4KXgrVuT3u8n8PGkVQoYxgvPdboSDGiz23ryBH2rEVOQYJh0Q3BQCJhwQLCZ_VKM_YoY7P-7ggINVwwhGJR1_nYI30KU4HTJgj6lDUBkUDHgHTvU-nCA6OKTY--yHDm4uv9wU2_i9KMEPO6_9GFN-Rp44FTI-f6gX5NuH91-3H4vrz1eftpfXhWFNKwpXMauY2Dinmrpta74x1jjaVo4ZW5ZtVXNuLG1U44yoOG8UWqZ1pWdIcKWrC_JqmTvfczthHuV8lcEQ1IBxyrJiteANF0zMaL2gJsWcEzp5SL5X6SQZlfdW5F4uVuS9FblYmWMvHzZMukf7L_RXwwy8XQCc_zx6TDIbj4NB6xOaUdro_7_hDzc2owM</recordid><startdate>202501</startdate><enddate>202501</enddate><creator>Kraevaya, Olga A.</creator><creator>Bolshakova, Valeriya S.</creator><creator>Slita, Alexander V.</creator><creator>Esaulkova, Iana L.</creator><creator>Zhilenkov, Alexander V.</creator><creator>Mikhalsky, Mikhail G.</creator><creator>Sinegubova, Ekaterina O.</creator><creator>Voronov, Ilya I.</creator><creator>Peregudov, Alexander S.</creator><creator>Shestakov, Alexander F.</creator><creator>Zarubaev, Vladimir V.</creator><creator>Troshin, Pavel A.</creator><general>Elsevier Inc</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>7X8</scope></search><sort><creationdate>202501</creationdate><title>Buckyballs to fight pandemic: Water-soluble fullerene derivatives with pendant carboxylic groups emerge as a new family of promising SARS-CoV-2 inhibitors</title><author>Kraevaya, Olga A. ; Bolshakova, Valeriya S. ; Slita, Alexander V. ; Esaulkova, Iana L. ; Zhilenkov, Alexander V. ; Mikhalsky, Mikhail G. ; Sinegubova, Ekaterina O. ; Voronov, Ilya I. ; Peregudov, Alexander S. ; Shestakov, Alexander F. ; Zarubaev, Vladimir V. ; Troshin, Pavel A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1569-f31da198ffa5466478cdcf063f1cd2263477cd05a5fc93775aed1bb3bcf097ab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>Antiviral activity</topic><topic>Antiviral Agents - chemical synthesis</topic><topic>Antiviral Agents - chemistry</topic><topic>Antiviral Agents - pharmacology</topic><topic>Carboxylic Acids - chemical synthesis</topic><topic>Carboxylic Acids - chemistry</topic><topic>Carboxylic Acids - pharmacology</topic><topic>Coronavirus 3C Proteases - antagonists & inhibitors</topic><topic>Coronavirus 3C Proteases - metabolism</topic><topic>COVID-19 - epidemiology</topic><topic>COVID-19 - virology</topic><topic>COVID-19 Drug Treatment</topic><topic>Dose-Response Relationship, Drug</topic><topic>Fullerene derivatives</topic><topic>Fullerenes - chemistry</topic><topic>Fullerenes - pharmacology</topic><topic>Humans</topic><topic>Mechanism</topic><topic>Microbial Sensitivity Tests</topic><topic>Molecular Docking Simulation</topic><topic>Molecular Structure</topic><topic>SARS-CoV-2</topic><topic>SARS-CoV-2 - drug effects</topic><topic>Solubility</topic><topic>Spike Glycoprotein, Coronavirus - antagonists & inhibitors</topic><topic>Spike Glycoprotein, Coronavirus - chemistry</topic><topic>Spike Glycoprotein, Coronavirus - metabolism</topic><topic>Structure-Activity Relationship</topic><topic>Water - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kraevaya, Olga A.</creatorcontrib><creatorcontrib>Bolshakova, Valeriya S.</creatorcontrib><creatorcontrib>Slita, Alexander V.</creatorcontrib><creatorcontrib>Esaulkova, Iana L.</creatorcontrib><creatorcontrib>Zhilenkov, Alexander V.</creatorcontrib><creatorcontrib>Mikhalsky, Mikhail G.</creatorcontrib><creatorcontrib>Sinegubova, Ekaterina O.</creatorcontrib><creatorcontrib>Voronov, Ilya I.</creatorcontrib><creatorcontrib>Peregudov, Alexander S.</creatorcontrib><creatorcontrib>Shestakov, Alexander F.</creatorcontrib><creatorcontrib>Zarubaev, Vladimir V.</creatorcontrib><creatorcontrib>Troshin, Pavel A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kraevaya, Olga A.</au><au>Bolshakova, Valeriya S.</au><au>Slita, Alexander V.</au><au>Esaulkova, Iana L.</au><au>Zhilenkov, Alexander V.</au><au>Mikhalsky, Mikhail G.</au><au>Sinegubova, Ekaterina O.</au><au>Voronov, Ilya I.</au><au>Peregudov, Alexander S.</au><au>Shestakov, Alexander F.</au><au>Zarubaev, Vladimir V.</au><au>Troshin, Pavel A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Buckyballs to fight pandemic: Water-soluble fullerene derivatives with pendant carboxylic groups emerge as a new family of promising SARS-CoV-2 inhibitors</atitle><jtitle>Bioorganic chemistry</jtitle><addtitle>Bioorg Chem</addtitle><date>2025-01</date><risdate>2025</risdate><volume>154</volume><spage>108097</spage><pages>108097-</pages><artnum>108097</artnum><issn>0045-2068</issn><issn>1090-2120</issn><eissn>1090-2120</eissn><abstract>[Display omitted]
•Individual water-soluble fullerene derivatives were shown to inhibit SARS-CoV-2.•High selectivity indexes up to 214 were achieved for leading compounds.•Time-of-addition test revealed spike protein and main protease as probable targets.
Herein, we present the first experimental study of individual water-soluble fullerene derivatives proving their ability to inhibit SARS-CoV-2 in vitro. The initial screening allowed us to identify a few new compounds that have demonstrated pronounced antiviral activity with IC50 values as low as 390 nM and selectivity indexes reaching 214. Time-of-addition analysis and molecular docking results suggested that the viral protease and/or the spike protein are the most probable targets inhibited by the fullerene derivatives. Further rational design of fullerene derivatives might lead to the development of compounds with further enhanced antiviral activity and decreased toxicity.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>39729769</pmid><doi>10.1016/j.bioorg.2024.108097</doi></addata></record> |
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| ispartof | Bioorganic chemistry, 2025-01, Vol.154, p.108097, Article 108097 |
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| subjects | Antiviral activity Antiviral Agents - chemical synthesis Antiviral Agents - chemistry Antiviral Agents - pharmacology Carboxylic Acids - chemical synthesis Carboxylic Acids - chemistry Carboxylic Acids - pharmacology Coronavirus 3C Proteases - antagonists & inhibitors Coronavirus 3C Proteases - metabolism COVID-19 - epidemiology COVID-19 - virology COVID-19 Drug Treatment Dose-Response Relationship, Drug Fullerene derivatives Fullerenes - chemistry Fullerenes - pharmacology Humans Mechanism Microbial Sensitivity Tests Molecular Docking Simulation Molecular Structure SARS-CoV-2 SARS-CoV-2 - drug effects Solubility Spike Glycoprotein, Coronavirus - antagonists & inhibitors Spike Glycoprotein, Coronavirus - chemistry Spike Glycoprotein, Coronavirus - metabolism Structure-Activity Relationship Water - chemistry |
| title | Buckyballs to fight pandemic: Water-soluble fullerene derivatives with pendant carboxylic groups emerge as a new family of promising SARS-CoV-2 inhibitors |
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