Inhibitory activities of alginate phosphate and sulfate derivatives against SARS-CoV-2 in vitro
Alginate derivatives have been demonstrated remarkable antiviral activities. Here we firstly identified polymannuronate phosphate (PMP) as a highly potential anti-SARS-CoV-2 agent. The structure-activity relationship showed polymannuronate monophosphate (PMPD, Mw: 5.8 kDa, P%: 8.7 %) was the most ef...
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| Veröffentlicht in: | International journal of biological macromolecules 2023-02, Vol.227, p.316-328 |
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| creator | Yang, Cheng Li, Dan Wang, Shixin Xu, Meijie Wang, Dingfu Li, Xin Xu, Ximing Li, Chunxia |
| description | Alginate derivatives have been demonstrated remarkable antiviral activities. Here we firstly identified polymannuronate phosphate (PMP) as a highly potential anti-SARS-CoV-2 agent. The structure-activity relationship showed polymannuronate monophosphate (PMPD, Mw: 5.8 kDa, P%: 8.7 %) was the most effective component to block the interaction of spike to ACE2 with an IC50 of 85.5 nM. Surface plasmon resonance study indicated that PMPD could bind to spike receptor binding domain (RBD) with the KD value of 78.59 nM. Molecular docking further suggested that the probable binding site of PMPD to spike RBD protein is the interaction interface between spike and ACE2. PMPD has the potential to inhibit the SARS-CoV-2 infection in an independent manner of heparan sulfate proteoglycans. In addition, polyguluronate sulfate (PGS) and propylene glycol alginate sodium sulfate (PSS) unexpectedly showed 3CLpro inhibition with an IC50 of 1.20 μM and 1.42 μM respectively. The polyguluronate backbone and sulfate group played pivotal roles in the 3CLpro inhibition. Overall, this study revealed the potential of PMPD as a novel agent against SARS-CoV-2. It also provided a theoretical basis for further study on the role of PGS and PSS as 3CLpro inhibitors.
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| doi_str_mv | 10.1016/j.ijbiomac.2022.11.311 |
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[Display omitted]</description><identifier>ISSN: 0141-8130</identifier><identifier>EISSN: 1879-0003</identifier><identifier>DOI: 10.1016/j.ijbiomac.2022.11.311</identifier><identifier>PMID: 36481336</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>3CLpro ; Alginate derivatives ; Alginates - pharmacology ; Angiotensin-Converting Enzyme 2 ; COVID-19 ; Humans ; Molecular Docking Simulation ; Phosphates ; Protein Binding ; SARS-CoV-2 ; Spike protein ; Sulfates</subject><ispartof>International journal of biological macromolecules, 2023-02, Vol.227, p.316-328</ispartof><rights>2022 Elsevier B.V.</rights><rights>Copyright © 2022 Elsevier B.V. All rights reserved.</rights><rights>2022 Published by Elsevier B.V. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c471t-4cc7a674ddcbcdc76062bacac1b746875559df885ba0740981422d714730df983</citedby><cites>FETCH-LOGICAL-c471t-4cc7a674ddcbcdc76062bacac1b746875559df885ba0740981422d714730df983</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijbiomac.2022.11.311$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36481336$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Cheng</creatorcontrib><creatorcontrib>Li, Dan</creatorcontrib><creatorcontrib>Wang, Shixin</creatorcontrib><creatorcontrib>Xu, Meijie</creatorcontrib><creatorcontrib>Wang, Dingfu</creatorcontrib><creatorcontrib>Li, Xin</creatorcontrib><creatorcontrib>Xu, Ximing</creatorcontrib><creatorcontrib>Li, Chunxia</creatorcontrib><title>Inhibitory activities of alginate phosphate and sulfate derivatives against SARS-CoV-2 in vitro</title><title>International journal of biological macromolecules</title><addtitle>Int J Biol Macromol</addtitle><description>Alginate derivatives have been demonstrated remarkable antiviral activities. Here we firstly identified polymannuronate phosphate (PMP) as a highly potential anti-SARS-CoV-2 agent. The structure-activity relationship showed polymannuronate monophosphate (PMPD, Mw: 5.8 kDa, P%: 8.7 %) was the most effective component to block the interaction of spike to ACE2 with an IC50 of 85.5 nM. Surface plasmon resonance study indicated that PMPD could bind to spike receptor binding domain (RBD) with the KD value of 78.59 nM. Molecular docking further suggested that the probable binding site of PMPD to spike RBD protein is the interaction interface between spike and ACE2. PMPD has the potential to inhibit the SARS-CoV-2 infection in an independent manner of heparan sulfate proteoglycans. In addition, polyguluronate sulfate (PGS) and propylene glycol alginate sodium sulfate (PSS) unexpectedly showed 3CLpro inhibition with an IC50 of 1.20 μM and 1.42 μM respectively. The polyguluronate backbone and sulfate group played pivotal roles in the 3CLpro inhibition. Overall, this study revealed the potential of PMPD as a novel agent against SARS-CoV-2. It also provided a theoretical basis for further study on the role of PGS and PSS as 3CLpro inhibitors.
[Display omitted]</description><subject>3CLpro</subject><subject>Alginate derivatives</subject><subject>Alginates - pharmacology</subject><subject>Angiotensin-Converting Enzyme 2</subject><subject>COVID-19</subject><subject>Humans</subject><subject>Molecular Docking Simulation</subject><subject>Phosphates</subject><subject>Protein Binding</subject><subject>SARS-CoV-2</subject><subject>Spike protein</subject><subject>Sulfates</subject><issn>0141-8130</issn><issn>1879-0003</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9rGzEQxUVpaNy0XyHssZfdaiSttHspDSZtA4FC_vQqtJLWHrOWXGltyLevjJPQnnrSMPq9N8M8Qi6BNkBBft40uBkwbo1tGGWsAWg4wBuygE71NaWUvyULCgLqDjg9J-9z3pSubKF7R865FKXN5YLom7DGAeeYnipjZzzgjD5XcazMtMJgZl_t1jHv1sfKBFfl_TQea-cTHkwRFNqsDIY8V_dXd_f1Mv6qWYWhKlYpfiBno5my__j8XpDHb9cPyx_17c_vN8ur29oKBXMtrFVGKuGcHayzSlLJBmONhUEJ2am2bXs3dl07GKoE7TsQjDkFQnHqxr7jF-TLyXe3H7beWR_mZCa9S7g16UlHg_rfn4BrvYoH3SsGXPXF4NOzQYq_9z7PeovZ-mkywcd91ky1vFy4ZW1B5Qm1Keac_Pg6Bqg-pqM3-iUdfUxHA-iiLcLLv5d8lb3EUYCvJ8CXUx3QJ50t-mC9w-TtrF3E_834Ax1mpbk</recordid><startdate>20230201</startdate><enddate>20230201</enddate><creator>Yang, Cheng</creator><creator>Li, Dan</creator><creator>Wang, Shixin</creator><creator>Xu, Meijie</creator><creator>Wang, Dingfu</creator><creator>Li, Xin</creator><creator>Xu, Ximing</creator><creator>Li, Chunxia</creator><general>Elsevier B.V</general><general>Published by Elsevier 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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20230201</creationdate><title>Inhibitory activities of alginate phosphate and sulfate derivatives against SARS-CoV-2 in vitro</title><author>Yang, Cheng ; Li, Dan ; Wang, Shixin ; Xu, Meijie ; Wang, Dingfu ; Li, Xin ; Xu, Ximing ; Li, Chunxia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c471t-4cc7a674ddcbcdc76062bacac1b746875559df885ba0740981422d714730df983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>3CLpro</topic><topic>Alginate derivatives</topic><topic>Alginates - pharmacology</topic><topic>Angiotensin-Converting Enzyme 2</topic><topic>COVID-19</topic><topic>Humans</topic><topic>Molecular Docking Simulation</topic><topic>Phosphates</topic><topic>Protein Binding</topic><topic>SARS-CoV-2</topic><topic>Spike protein</topic><topic>Sulfates</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Cheng</creatorcontrib><creatorcontrib>Li, Dan</creatorcontrib><creatorcontrib>Wang, Shixin</creatorcontrib><creatorcontrib>Xu, Meijie</creatorcontrib><creatorcontrib>Wang, Dingfu</creatorcontrib><creatorcontrib>Li, Xin</creatorcontrib><creatorcontrib>Xu, Ximing</creatorcontrib><creatorcontrib>Li, Chunxia</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of biological macromolecules</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Cheng</au><au>Li, Dan</au><au>Wang, Shixin</au><au>Xu, Meijie</au><au>Wang, Dingfu</au><au>Li, Xin</au><au>Xu, Ximing</au><au>Li, Chunxia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibitory activities of alginate phosphate and sulfate derivatives against SARS-CoV-2 in vitro</atitle><jtitle>International journal of biological macromolecules</jtitle><addtitle>Int J Biol Macromol</addtitle><date>2023-02-01</date><risdate>2023</risdate><volume>227</volume><spage>316</spage><epage>328</epage><pages>316-328</pages><issn>0141-8130</issn><eissn>1879-0003</eissn><abstract>Alginate derivatives have been demonstrated remarkable antiviral activities. Here we firstly identified polymannuronate phosphate (PMP) as a highly potential anti-SARS-CoV-2 agent. The structure-activity relationship showed polymannuronate monophosphate (PMPD, Mw: 5.8 kDa, P%: 8.7 %) was the most effective component to block the interaction of spike to ACE2 with an IC50 of 85.5 nM. Surface plasmon resonance study indicated that PMPD could bind to spike receptor binding domain (RBD) with the KD value of 78.59 nM. Molecular docking further suggested that the probable binding site of PMPD to spike RBD protein is the interaction interface between spike and ACE2. PMPD has the potential to inhibit the SARS-CoV-2 infection in an independent manner of heparan sulfate proteoglycans. In addition, polyguluronate sulfate (PGS) and propylene glycol alginate sodium sulfate (PSS) unexpectedly showed 3CLpro inhibition with an IC50 of 1.20 μM and 1.42 μM respectively. The polyguluronate backbone and sulfate group played pivotal roles in the 3CLpro inhibition. Overall, this study revealed the potential of PMPD as a novel agent against SARS-CoV-2. It also provided a theoretical basis for further study on the role of PGS and PSS as 3CLpro inhibitors.
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| subjects | 3CLpro Alginate derivatives Alginates - pharmacology Angiotensin-Converting Enzyme 2 COVID-19 Humans Molecular Docking Simulation Phosphates Protein Binding SARS-CoV-2 Spike protein Sulfates |
| title | Inhibitory activities of alginate phosphate and sulfate derivatives against SARS-CoV-2 in vitro |
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