First structure–activity relationship analysis of SARS-CoV-2 virus main protease (Mpro) inhibitors: an endeavor on COVID-19 drug discovery
Main protease (Mpro) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) intervenes in the replication and transcription processes of the virus. Hence, it is a lucrative target for anti-viral drug development. In this study, molecular modeling analyses were performed on the structure act...
Gespeichert in:
| Veröffentlicht in: | Molecular diversity 2021-08, Vol.25 (3), p.1827-1838 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1838 |
|---|---|
| container_issue | 3 |
| container_start_page | 1827 |
| container_title | Molecular diversity |
| container_volume | 25 |
| creator | Amin, Sk. Abdul Banerjee, Suvankar Singh, Samayaditya Qureshi, Insaf Ahmed Gayen, Shovanlal Jha, Tarun |
| description | Main protease (Mpro) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) intervenes in the replication and transcription processes of the virus. Hence, it is a lucrative target for anti-viral drug development. In this study, molecular modeling analyses were performed on the structure activity data of recently reported diverse SARS-CoV-2 Mpro inhibitors to understand the structural requirements for higher inhibitory activity. The classification-based quantitative structure–activity relationship (QSAR) models were generated between SARS-CoV-2 Mpro inhibitory activities and different descriptors. Identification of structural fingerprints to increase or decrease in the inhibitory activity was mapped for possible inclusion/exclusion of these fingerprints in the lead optimization process. Challenges in ADME properties of protease inhibitors were also discussed to overcome the problems of oral bioavailability. Further, depending on the modeling results, we have proposed novel as well as potent SARS-CoV-2 Mpro inhibitors.
Graphic Abstract |
| doi_str_mv | 10.1007/s11030-020-10166-3 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7782049</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2558266597</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-df30ab72c42e61a276fb017f48cad778dc89d148fc240a5fd7d6a919582dcd873</originalsourceid><addsrcrecordid>eNp9kU1uFDEQhVsIRH7gAiyQJTawMJTt7nY3i0jRQCBSUCQCETvLY7tnHM3YQ9nd0uxyAHbckJPgMCHAhpVLqve-V_KrqicMXjIA-SoxBgIocKAMWNtSca_aZ40UtAH25X6ZRcco63u2Vx2kdAVQbEw8rPaEqAGga_arbyceUyYp42jyiO7H9Xdtsp983hJ0K519DGnpN0QHvdomn0gcyMXxxws6i5eUk8njmMha-0A2GLPTyZHnH8r4gviw9HOfI6bXxU1csE5PEUkMZHZ-efqmXEYsjgtifTJxcrh9VD0Y9Cq5x7fvYfX55O2n2Xt6dv7udHZ8Rk0t60ztIEDPJTc1dy3TXLbDHJgc6s5oK2VnTddbVneD4TXoZrDStrpnfdNxa2wnxWF1tONuxvnaWeNCRr1SG_RrjVsVtVf_boJfqkWcVIFzqPsCeHYLwPh1dCmrqzhi-aGkeFNi2rbpb2L4TmUwpoRuuEtgoG4aVLsGVWlQ_WpQiWJ6-vdtd5bflRWB2AlSWYWFwz_Z_8H-BC0Dqe8</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2558266597</pqid></control><display><type>article</type><title>First structure–activity relationship analysis of SARS-CoV-2 virus main protease (Mpro) inhibitors: an endeavor on COVID-19 drug discovery</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Amin, Sk. Abdul ; Banerjee, Suvankar ; Singh, Samayaditya ; Qureshi, Insaf Ahmed ; Gayen, Shovanlal ; Jha, Tarun</creator><creatorcontrib>Amin, Sk. Abdul ; Banerjee, Suvankar ; Singh, Samayaditya ; Qureshi, Insaf Ahmed ; Gayen, Shovanlal ; Jha, Tarun</creatorcontrib><description>Main protease (Mpro) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) intervenes in the replication and transcription processes of the virus. Hence, it is a lucrative target for anti-viral drug development. In this study, molecular modeling analyses were performed on the structure activity data of recently reported diverse SARS-CoV-2 Mpro inhibitors to understand the structural requirements for higher inhibitory activity. The classification-based quantitative structure–activity relationship (QSAR) models were generated between SARS-CoV-2 Mpro inhibitory activities and different descriptors. Identification of structural fingerprints to increase or decrease in the inhibitory activity was mapped for possible inclusion/exclusion of these fingerprints in the lead optimization process. Challenges in ADME properties of protease inhibitors were also discussed to overcome the problems of oral bioavailability. Further, depending on the modeling results, we have proposed novel as well as potent SARS-CoV-2 Mpro inhibitors.
Graphic Abstract</description><identifier>ISSN: 1381-1991</identifier><identifier>EISSN: 1573-501X</identifier><identifier>DOI: 10.1007/s11030-020-10166-3</identifier><identifier>PMID: 33400085</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Biochemistry ; Biological Availability ; Biomedical and Life Sciences ; Coronavirus 3C Proteases - antagonists & inhibitors ; Coronavirus 3C Proteases - chemistry ; Coronaviruses ; Drug development ; Life Sciences ; Models, Molecular ; Organic Chemistry ; Original ; Original Article ; Pharmacy ; Polymer Sciences ; Protease Inhibitors - chemistry ; Protease Inhibitors - pharmacokinetics ; Protease Inhibitors - pharmacology ; Protein Conformation ; SARS-CoV-2 - drug effects ; SARS-CoV-2 - enzymology ; Severe acute respiratory syndrome coronavirus 2 ; Structure-Activity Relationship</subject><ispartof>Molecular diversity, 2021-08, Vol.25 (3), p.1827-1838</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-df30ab72c42e61a276fb017f48cad778dc89d148fc240a5fd7d6a919582dcd873</citedby><cites>FETCH-LOGICAL-c474t-df30ab72c42e61a276fb017f48cad778dc89d148fc240a5fd7d6a919582dcd873</cites><orcidid>0000-0002-9996-738X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11030-020-10166-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11030-020-10166-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33400085$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Amin, Sk. Abdul</creatorcontrib><creatorcontrib>Banerjee, Suvankar</creatorcontrib><creatorcontrib>Singh, Samayaditya</creatorcontrib><creatorcontrib>Qureshi, Insaf Ahmed</creatorcontrib><creatorcontrib>Gayen, Shovanlal</creatorcontrib><creatorcontrib>Jha, Tarun</creatorcontrib><title>First structure–activity relationship analysis of SARS-CoV-2 virus main protease (Mpro) inhibitors: an endeavor on COVID-19 drug discovery</title><title>Molecular diversity</title><addtitle>Mol Divers</addtitle><addtitle>Mol Divers</addtitle><description>Main protease (Mpro) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) intervenes in the replication and transcription processes of the virus. Hence, it is a lucrative target for anti-viral drug development. In this study, molecular modeling analyses were performed on the structure activity data of recently reported diverse SARS-CoV-2 Mpro inhibitors to understand the structural requirements for higher inhibitory activity. The classification-based quantitative structure–activity relationship (QSAR) models were generated between SARS-CoV-2 Mpro inhibitory activities and different descriptors. Identification of structural fingerprints to increase or decrease in the inhibitory activity was mapped for possible inclusion/exclusion of these fingerprints in the lead optimization process. Challenges in ADME properties of protease inhibitors were also discussed to overcome the problems of oral bioavailability. Further, depending on the modeling results, we have proposed novel as well as potent SARS-CoV-2 Mpro inhibitors.
Graphic Abstract</description><subject>Biochemistry</subject><subject>Biological Availability</subject><subject>Biomedical and Life Sciences</subject><subject>Coronavirus 3C Proteases - antagonists & inhibitors</subject><subject>Coronavirus 3C Proteases - chemistry</subject><subject>Coronaviruses</subject><subject>Drug development</subject><subject>Life Sciences</subject><subject>Models, Molecular</subject><subject>Organic Chemistry</subject><subject>Original</subject><subject>Original Article</subject><subject>Pharmacy</subject><subject>Polymer Sciences</subject><subject>Protease Inhibitors - chemistry</subject><subject>Protease Inhibitors - pharmacokinetics</subject><subject>Protease Inhibitors - pharmacology</subject><subject>Protein Conformation</subject><subject>SARS-CoV-2 - drug effects</subject><subject>SARS-CoV-2 - enzymology</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Structure-Activity Relationship</subject><issn>1381-1991</issn><issn>1573-501X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kU1uFDEQhVsIRH7gAiyQJTawMJTt7nY3i0jRQCBSUCQCETvLY7tnHM3YQ9nd0uxyAHbckJPgMCHAhpVLqve-V_KrqicMXjIA-SoxBgIocKAMWNtSca_aZ40UtAH25X6ZRcco63u2Vx2kdAVQbEw8rPaEqAGga_arbyceUyYp42jyiO7H9Xdtsp983hJ0K519DGnpN0QHvdomn0gcyMXxxws6i5eUk8njmMha-0A2GLPTyZHnH8r4gviw9HOfI6bXxU1csE5PEUkMZHZ-efqmXEYsjgtifTJxcrh9VD0Y9Cq5x7fvYfX55O2n2Xt6dv7udHZ8Rk0t60ztIEDPJTc1dy3TXLbDHJgc6s5oK2VnTddbVneD4TXoZrDStrpnfdNxa2wnxWF1tONuxvnaWeNCRr1SG_RrjVsVtVf_boJfqkWcVIFzqPsCeHYLwPh1dCmrqzhi-aGkeFNi2rbpb2L4TmUwpoRuuEtgoG4aVLsGVWlQ_WpQiWJ6-vdtd5bflRWB2AlSWYWFwz_Z_8H-BC0Dqe8</recordid><startdate>20210801</startdate><enddate>20210801</enddate><creator>Amin, Sk. Abdul</creator><creator>Banerjee, Suvankar</creator><creator>Singh, Samayaditya</creator><creator>Qureshi, Insaf Ahmed</creator><creator>Gayen, Shovanlal</creator><creator>Jha, Tarun</creator><general>Springer International Publishing</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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9996-738X</orcidid></search><sort><creationdate>20210801</creationdate><title>First structure–activity relationship analysis of SARS-CoV-2 virus main protease (Mpro) inhibitors: an endeavor on COVID-19 drug discovery</title><author>Amin, Sk. Abdul ; Banerjee, Suvankar ; Singh, Samayaditya ; Qureshi, Insaf Ahmed ; Gayen, Shovanlal ; Jha, Tarun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-df30ab72c42e61a276fb017f48cad778dc89d148fc240a5fd7d6a919582dcd873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Biochemistry</topic><topic>Biological Availability</topic><topic>Biomedical and Life Sciences</topic><topic>Coronavirus 3C Proteases - antagonists & inhibitors</topic><topic>Coronavirus 3C Proteases - chemistry</topic><topic>Coronaviruses</topic><topic>Drug development</topic><topic>Life Sciences</topic><topic>Models, Molecular</topic><topic>Organic Chemistry</topic><topic>Original</topic><topic>Original Article</topic><topic>Pharmacy</topic><topic>Polymer Sciences</topic><topic>Protease Inhibitors - chemistry</topic><topic>Protease Inhibitors - pharmacokinetics</topic><topic>Protease Inhibitors - pharmacology</topic><topic>Protein Conformation</topic><topic>SARS-CoV-2 - drug effects</topic><topic>SARS-CoV-2 - enzymology</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Amin, Sk. Abdul</creatorcontrib><creatorcontrib>Banerjee, Suvankar</creatorcontrib><creatorcontrib>Singh, Samayaditya</creatorcontrib><creatorcontrib>Qureshi, Insaf Ahmed</creatorcontrib><creatorcontrib>Gayen, Shovanlal</creatorcontrib><creatorcontrib>Jha, Tarun</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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</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>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular diversity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Amin, Sk. Abdul</au><au>Banerjee, Suvankar</au><au>Singh, Samayaditya</au><au>Qureshi, Insaf Ahmed</au><au>Gayen, Shovanlal</au><au>Jha, Tarun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>First structure–activity relationship analysis of SARS-CoV-2 virus main protease (Mpro) inhibitors: an endeavor on COVID-19 drug discovery</atitle><jtitle>Molecular diversity</jtitle><stitle>Mol Divers</stitle><addtitle>Mol Divers</addtitle><date>2021-08-01</date><risdate>2021</risdate><volume>25</volume><issue>3</issue><spage>1827</spage><epage>1838</epage><pages>1827-1838</pages><issn>1381-1991</issn><eissn>1573-501X</eissn><abstract>Main protease (Mpro) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) intervenes in the replication and transcription processes of the virus. Hence, it is a lucrative target for anti-viral drug development. In this study, molecular modeling analyses were performed on the structure activity data of recently reported diverse SARS-CoV-2 Mpro inhibitors to understand the structural requirements for higher inhibitory activity. The classification-based quantitative structure–activity relationship (QSAR) models were generated between SARS-CoV-2 Mpro inhibitory activities and different descriptors. Identification of structural fingerprints to increase or decrease in the inhibitory activity was mapped for possible inclusion/exclusion of these fingerprints in the lead optimization process. Challenges in ADME properties of protease inhibitors were also discussed to overcome the problems of oral bioavailability. Further, depending on the modeling results, we have proposed novel as well as potent SARS-CoV-2 Mpro inhibitors.
Graphic Abstract</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>33400085</pmid><doi>10.1007/s11030-020-10166-3</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-9996-738X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1381-1991 |
| ispartof | Molecular diversity, 2021-08, Vol.25 (3), p.1827-1838 |
| issn | 1381-1991 1573-501X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7782049 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Biochemistry Biological Availability Biomedical and Life Sciences Coronavirus 3C Proteases - antagonists & inhibitors Coronavirus 3C Proteases - chemistry Coronaviruses Drug development Life Sciences Models, Molecular Organic Chemistry Original Original Article Pharmacy Polymer Sciences Protease Inhibitors - chemistry Protease Inhibitors - pharmacokinetics Protease Inhibitors - pharmacology Protein Conformation SARS-CoV-2 - drug effects SARS-CoV-2 - enzymology Severe acute respiratory syndrome coronavirus 2 Structure-Activity Relationship |
| title | First structure–activity relationship analysis of SARS-CoV-2 virus main protease (Mpro) inhibitors: an endeavor on COVID-19 drug discovery |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T04%3A05%3A32IST&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=First%20structure%E2%80%93activity%20relationship%20analysis%20of%20SARS-CoV-2%20virus%20main%20protease%20(Mpro)%20inhibitors:%20an%20endeavor%20on%20COVID-19%20drug%20discovery&rft.jtitle=Molecular%20diversity&rft.au=Amin,%20Sk.%20Abdul&rft.date=2021-08-01&rft.volume=25&rft.issue=3&rft.spage=1827&rft.epage=1838&rft.pages=1827-1838&rft.issn=1381-1991&rft.eissn=1573-501X&rft_id=info:doi/10.1007/s11030-020-10166-3&rft_dat=%3Cproquest_pubme%3E2558266597%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=2558266597&rft_id=info:pmid/33400085&rfr_iscdi=true |