Enterovirus Inhibition by Hinged Aromatic Compounds with Polynuclei

The modern world has no available drugs for the treatment of enteroviruses (EV), which affect millions of people worldwide each year. The EV71 is a major causative disease for hand, foot, and mouth disease; sometimes it is associated with severe central nervous system diseases. Treatment for enterov...

Full description

Saved in:
Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2020-08, Vol.25 (17), p.3821
Main Authors: Hwu, Jih Ru, Panja, Avijit, Jayakumar, Srinivasan, Tsay, Shwu-Chen, Tan, Kui-Thong, Huang, Wen-Chieh, Hu, Yu-Chen, Leyssen, Pieter, Neyts, Johan
Format: Article
Language:English
Subjects:
Animals
Antiviral activity
Antiviral agents
Antiviral Agents - chemical synthesis
Antiviral Agents - chemistry
Antiviral Agents - pharmacology
Aromatic compounds
Aseptic meningitis
Benzene
Carbon
Central nervous system
Central nervous system diseases
Chemical synthesis
Chlorocebus aethiops
Disease
Drugs
enterovirus
Enterovirus A, Human - growth & development
Enterovirus Infections - drug therapy
Enterovirus Infections - metabolism
Enteroviruses
furan
Hand-foot-and-mouth disease
Health services
hinged bond
Hydrocarbons
Infections
Medical treatment
Meningitis
Morpholine
Pyrazole
RNA polymerase
Selectivity
thiophene
Vero Cells
Viruses
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c493t-7cabf3bf94ebf82d21696f0a5b8f62612da8475930270d520fb5daea4bce24a83
cites cdi_FETCH-LOGICAL-c493t-7cabf3bf94ebf82d21696f0a5b8f62612da8475930270d520fb5daea4bce24a83
container_end_page
container_issue 17
container_start_page 3821
container_title Molecules (Basel, Switzerland)
container_volume 25
creator Hwu, Jih Ru
Panja, Avijit
Jayakumar, Srinivasan
Tsay, Shwu-Chen
Tan, Kui-Thong
Huang, Wen-Chieh
Hu, Yu-Chen
Leyssen, Pieter
Neyts, Johan
description The modern world has no available drugs for the treatment of enteroviruses (EV), which affect millions of people worldwide each year. The EV71 is a major causative disease for hand, foot, and mouth disease; sometimes it is associated with severe central nervous system diseases. Treatment for enteroviral infection is mainly supportive; treatment for aseptic meningitis caused by enteroviruses is also generally symptomatic. Upon the urgent request of new anti-enterovirus drugs, a series of hinged aromatic compounds with polynulei were synthesized through two different chemical pathways. Among these morpholine-furan/thiophene/pyrrole-benzene-pyrazole conjugates, three new agents exhibited inhibitory activity with EC = 2.29-6.16 μM toward EV71 strain BrCr in RD cells. Their selectivity index values were reached as high as 33.4. Their structure-activity relationship was deduced that a thiophene derivative with morpholine and trifluorobenzene rings showed the greatest antiviral activity, with EC = 2.29 μM.
doi_str_mv 10.3390/molecules25173821
format article
fullrecord <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_056329c078e74be4bedf8f2e99135330</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_056329c078e74be4bedf8f2e99135330</doaj_id><sourcerecordid>2437405761</sourcerecordid><originalsourceid>FETCH-LOGICAL-c493t-7cabf3bf94ebf82d21696f0a5b8f62612da8475930270d520fb5daea4bce24a83</originalsourceid><addsrcrecordid>eNplkUtrGzEURkVpaNK0P6CbMtBNN270HI02hWDSxhBIFu1a6HFly8xIrjST4H_faZyGPEAgcXXu4UofQp8I_saYwmdD7sFNPVQqiGQdJW_QCeEULxjm6u2T8zF6X-sWY0o4Ee_QMaMdpy0XJ2h5kUYo-TaWqTartIk2jjGnxu6by5jW4JvzkgczRtcs87DLU_K1uYvjprnJ_T5Nrof4AR0F01f4-LCfot8_Ln4tLxdX1z9Xy_OrheOKjQvpjA3MBsXBho56SlrVBmyE7UJLW0K96bgUimEqsRcUByu8AcOtA8pNx07R6uD12Wz1rsTBlL3OJur7Qi5rbco8aQ8ai5ZR5bDsQHIL8_KhCxSUIkwwhmfX94NrN9kBvIM0FtM_kz6_SXGj1_lWS4GZJHQWfH0QlPxngjrqIVYHfW8S5KlqypnkWMiWzOiXF-g2TyXNX3VPtXyOTs0UOVCu5FoLhMdhCNb_4tav4p57Pj99xWPH_3zZX1JjqKU</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2437643829</pqid></control><display><type>article</type><title>Enterovirus Inhibition by Hinged Aromatic Compounds with Polynuclei</title><source>Open Access: PubMed Central</source><source>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</source><source>Coronavirus Research Database</source><creator>Hwu, Jih Ru ; Panja, Avijit ; Jayakumar, Srinivasan ; Tsay, Shwu-Chen ; Tan, Kui-Thong ; Huang, Wen-Chieh ; Hu, Yu-Chen ; Leyssen, Pieter ; Neyts, Johan</creator><creatorcontrib>Hwu, Jih Ru ; Panja, Avijit ; Jayakumar, Srinivasan ; Tsay, Shwu-Chen ; Tan, Kui-Thong ; Huang, Wen-Chieh ; Hu, Yu-Chen ; Leyssen, Pieter ; Neyts, Johan</creatorcontrib><description>The modern world has no available drugs for the treatment of enteroviruses (EV), which affect millions of people worldwide each year. The EV71 is a major causative disease for hand, foot, and mouth disease; sometimes it is associated with severe central nervous system diseases. Treatment for enteroviral infection is mainly supportive; treatment for aseptic meningitis caused by enteroviruses is also generally symptomatic. Upon the urgent request of new anti-enterovirus drugs, a series of hinged aromatic compounds with polynulei were synthesized through two different chemical pathways. Among these morpholine-furan/thiophene/pyrrole-benzene-pyrazole conjugates, three new agents exhibited inhibitory activity with EC = 2.29-6.16 μM toward EV71 strain BrCr in RD cells. Their selectivity index values were reached as high as 33.4. Their structure-activity relationship was deduced that a thiophene derivative with morpholine and trifluorobenzene rings showed the greatest antiviral activity, with EC = 2.29 μM.</description><identifier>ISSN: 1420-3049</identifier><identifier>EISSN: 1420-3049</identifier><identifier>DOI: 10.3390/molecules25173821</identifier><identifier>PMID: 32842645</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animals ; Antiviral activity ; Antiviral agents ; Antiviral Agents - chemical synthesis ; Antiviral Agents - chemistry ; Antiviral Agents - pharmacology ; Aromatic compounds ; Aseptic meningitis ; Benzene ; Carbon ; Central nervous system ; Central nervous system diseases ; Chemical synthesis ; Chlorocebus aethiops ; Disease ; Drugs ; enterovirus ; Enterovirus A, Human - growth &amp; development ; Enterovirus Infections - drug therapy ; Enterovirus Infections - metabolism ; Enteroviruses ; furan ; Hand-foot-and-mouth disease ; Health services ; hinged bond ; Hydrocarbons ; Infections ; Medical treatment ; Meningitis ; Morpholine ; Pyrazole ; RNA polymerase ; Selectivity ; thiophene ; Vero Cells ; Viruses</subject><ispartof>Molecules (Basel, Switzerland), 2020-08, Vol.25 (17), p.3821</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-7cabf3bf94ebf82d21696f0a5b8f62612da8475930270d520fb5daea4bce24a83</citedby><cites>FETCH-LOGICAL-c493t-7cabf3bf94ebf82d21696f0a5b8f62612da8475930270d520fb5daea4bce24a83</cites><orcidid>0000-0002-1336-8547 ; 0000-0003-0585-3419</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2437643829/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2437643829?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,38516,43895,44590,53791,53793,74284,74998</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32842645$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hwu, Jih Ru</creatorcontrib><creatorcontrib>Panja, Avijit</creatorcontrib><creatorcontrib>Jayakumar, Srinivasan</creatorcontrib><creatorcontrib>Tsay, Shwu-Chen</creatorcontrib><creatorcontrib>Tan, Kui-Thong</creatorcontrib><creatorcontrib>Huang, Wen-Chieh</creatorcontrib><creatorcontrib>Hu, Yu-Chen</creatorcontrib><creatorcontrib>Leyssen, Pieter</creatorcontrib><creatorcontrib>Neyts, Johan</creatorcontrib><title>Enterovirus Inhibition by Hinged Aromatic Compounds with Polynuclei</title><title>Molecules (Basel, Switzerland)</title><addtitle>Molecules</addtitle><description>The modern world has no available drugs for the treatment of enteroviruses (EV), which affect millions of people worldwide each year. The EV71 is a major causative disease for hand, foot, and mouth disease; sometimes it is associated with severe central nervous system diseases. Treatment for enteroviral infection is mainly supportive; treatment for aseptic meningitis caused by enteroviruses is also generally symptomatic. Upon the urgent request of new anti-enterovirus drugs, a series of hinged aromatic compounds with polynulei were synthesized through two different chemical pathways. Among these morpholine-furan/thiophene/pyrrole-benzene-pyrazole conjugates, three new agents exhibited inhibitory activity with EC = 2.29-6.16 μM toward EV71 strain BrCr in RD cells. Their selectivity index values were reached as high as 33.4. Their structure-activity relationship was deduced that a thiophene derivative with morpholine and trifluorobenzene rings showed the greatest antiviral activity, with EC = 2.29 μM.</description><subject>Animals</subject><subject>Antiviral activity</subject><subject>Antiviral agents</subject><subject>Antiviral Agents - chemical synthesis</subject><subject>Antiviral Agents - chemistry</subject><subject>Antiviral Agents - pharmacology</subject><subject>Aromatic compounds</subject><subject>Aseptic meningitis</subject><subject>Benzene</subject><subject>Carbon</subject><subject>Central nervous system</subject><subject>Central nervous system diseases</subject><subject>Chemical synthesis</subject><subject>Chlorocebus aethiops</subject><subject>Disease</subject><subject>Drugs</subject><subject>enterovirus</subject><subject>Enterovirus A, Human - growth &amp; development</subject><subject>Enterovirus Infections - drug therapy</subject><subject>Enterovirus Infections - metabolism</subject><subject>Enteroviruses</subject><subject>furan</subject><subject>Hand-foot-and-mouth disease</subject><subject>Health services</subject><subject>hinged bond</subject><subject>Hydrocarbons</subject><subject>Infections</subject><subject>Medical treatment</subject><subject>Meningitis</subject><subject>Morpholine</subject><subject>Pyrazole</subject><subject>RNA polymerase</subject><subject>Selectivity</subject><subject>thiophene</subject><subject>Vero Cells</subject><subject>Viruses</subject><issn>1420-3049</issn><issn>1420-3049</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>COVID</sourceid><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNplkUtrGzEURkVpaNK0P6CbMtBNN270HI02hWDSxhBIFu1a6HFly8xIrjST4H_faZyGPEAgcXXu4UofQp8I_saYwmdD7sFNPVQqiGQdJW_QCeEULxjm6u2T8zF6X-sWY0o4Ee_QMaMdpy0XJ2h5kUYo-TaWqTartIk2jjGnxu6by5jW4JvzkgczRtcs87DLU_K1uYvjprnJ_T5Nrof4AR0F01f4-LCfot8_Ln4tLxdX1z9Xy_OrheOKjQvpjA3MBsXBho56SlrVBmyE7UJLW0K96bgUimEqsRcUByu8AcOtA8pNx07R6uD12Wz1rsTBlL3OJur7Qi5rbco8aQ8ai5ZR5bDsQHIL8_KhCxSUIkwwhmfX94NrN9kBvIM0FtM_kz6_SXGj1_lWS4GZJHQWfH0QlPxngjrqIVYHfW8S5KlqypnkWMiWzOiXF-g2TyXNX3VPtXyOTs0UOVCu5FoLhMdhCNb_4tav4p57Pj99xWPH_3zZX1JjqKU</recordid><startdate>20200822</startdate><enddate>20200822</enddate><creator>Hwu, Jih Ru</creator><creator>Panja, Avijit</creator><creator>Jayakumar, Srinivasan</creator><creator>Tsay, Shwu-Chen</creator><creator>Tan, Kui-Thong</creator><creator>Huang, Wen-Chieh</creator><creator>Hu, Yu-Chen</creator><creator>Leyssen, Pieter</creator><creator>Neyts, Johan</creator><general>MDPI AG</general><general>MDPI</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>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>COVID</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-1336-8547</orcidid><orcidid>https://orcid.org/0000-0003-0585-3419</orcidid></search><sort><creationdate>20200822</creationdate><title>Enterovirus Inhibition by Hinged Aromatic Compounds with Polynuclei</title><author>Hwu, Jih Ru ; Panja, Avijit ; Jayakumar, Srinivasan ; Tsay, Shwu-Chen ; Tan, Kui-Thong ; Huang, Wen-Chieh ; Hu, Yu-Chen ; Leyssen, Pieter ; Neyts, Johan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c493t-7cabf3bf94ebf82d21696f0a5b8f62612da8475930270d520fb5daea4bce24a83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Antiviral activity</topic><topic>Antiviral agents</topic><topic>Antiviral Agents - chemical synthesis</topic><topic>Antiviral Agents - chemistry</topic><topic>Antiviral Agents - pharmacology</topic><topic>Aromatic compounds</topic><topic>Aseptic meningitis</topic><topic>Benzene</topic><topic>Carbon</topic><topic>Central nervous system</topic><topic>Central nervous system diseases</topic><topic>Chemical synthesis</topic><topic>Chlorocebus aethiops</topic><topic>Disease</topic><topic>Drugs</topic><topic>enterovirus</topic><topic>Enterovirus A, Human - growth &amp; development</topic><topic>Enterovirus Infections - drug therapy</topic><topic>Enterovirus Infections - metabolism</topic><topic>Enteroviruses</topic><topic>furan</topic><topic>Hand-foot-and-mouth disease</topic><topic>Health services</topic><topic>hinged bond</topic><topic>Hydrocarbons</topic><topic>Infections</topic><topic>Medical treatment</topic><topic>Meningitis</topic><topic>Morpholine</topic><topic>Pyrazole</topic><topic>RNA polymerase</topic><topic>Selectivity</topic><topic>thiophene</topic><topic>Vero Cells</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hwu, Jih Ru</creatorcontrib><creatorcontrib>Panja, Avijit</creatorcontrib><creatorcontrib>Jayakumar, Srinivasan</creatorcontrib><creatorcontrib>Tsay, Shwu-Chen</creatorcontrib><creatorcontrib>Tan, Kui-Thong</creatorcontrib><creatorcontrib>Huang, Wen-Chieh</creatorcontrib><creatorcontrib>Hu, Yu-Chen</creatorcontrib><creatorcontrib>Leyssen, Pieter</creatorcontrib><creatorcontrib>Neyts, Johan</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>ProQuest_Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical 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)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Coronavirus Research Database</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>Molecules (Basel, Switzerland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hwu, Jih Ru</au><au>Panja, Avijit</au><au>Jayakumar, Srinivasan</au><au>Tsay, Shwu-Chen</au><au>Tan, Kui-Thong</au><au>Huang, Wen-Chieh</au><au>Hu, Yu-Chen</au><au>Leyssen, Pieter</au><au>Neyts, Johan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enterovirus Inhibition by Hinged Aromatic Compounds with Polynuclei</atitle><jtitle>Molecules (Basel, Switzerland)</jtitle><addtitle>Molecules</addtitle><date>2020-08-22</date><risdate>2020</risdate><volume>25</volume><issue>17</issue><spage>3821</spage><pages>3821-</pages><issn>1420-3049</issn><eissn>1420-3049</eissn><abstract>The modern world has no available drugs for the treatment of enteroviruses (EV), which affect millions of people worldwide each year. The EV71 is a major causative disease for hand, foot, and mouth disease; sometimes it is associated with severe central nervous system diseases. Treatment for enteroviral infection is mainly supportive; treatment for aseptic meningitis caused by enteroviruses is also generally symptomatic. Upon the urgent request of new anti-enterovirus drugs, a series of hinged aromatic compounds with polynulei were synthesized through two different chemical pathways. Among these morpholine-furan/thiophene/pyrrole-benzene-pyrazole conjugates, three new agents exhibited inhibitory activity with EC = 2.29-6.16 μM toward EV71 strain BrCr in RD cells. Their selectivity index values were reached as high as 33.4. Their structure-activity relationship was deduced that a thiophene derivative with morpholine and trifluorobenzene rings showed the greatest antiviral activity, with EC = 2.29 μM.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>32842645</pmid><doi>10.3390/molecules25173821</doi><orcidid>https://orcid.org/0000-0002-1336-8547</orcidid><orcidid>https://orcid.org/0000-0003-0585-3419</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1420-3049
ispartof Molecules (Basel, Switzerland), 2020-08, Vol.25 (17), p.3821
issn 1420-3049
1420-3049
language eng
recordid cdi_doaj_primary_oai_doaj_org_article_056329c078e74be4bedf8f2e99135330
source Open Access: PubMed Central; Publicly Available Content Database (Proquest) (PQ_SDU_P3); Coronavirus Research Database
subjects Animals
Antiviral activity
Antiviral agents
Antiviral Agents - chemical synthesis
Antiviral Agents - chemistry
Antiviral Agents - pharmacology
Aromatic compounds
Aseptic meningitis
Benzene
Carbon
Central nervous system
Central nervous system diseases
Chemical synthesis
Chlorocebus aethiops
Disease
Drugs
enterovirus
Enterovirus A, Human - growth & development
Enterovirus Infections - drug therapy
Enterovirus Infections - metabolism
Enteroviruses
furan
Hand-foot-and-mouth disease
Health services
hinged bond
Hydrocarbons
Infections
Medical treatment
Meningitis
Morpholine
Pyrazole
RNA polymerase
Selectivity
thiophene
Vero Cells
Viruses
title Enterovirus Inhibition by Hinged Aromatic Compounds with Polynuclei
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T17%3A18%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Enterovirus%20Inhibition%20by%20Hinged%20Aromatic%20Compounds%20with%20Polynuclei&rft.jtitle=Molecules%20(Basel,%20Switzerland)&rft.au=Hwu,%20Jih%20Ru&rft.date=2020-08-22&rft.volume=25&rft.issue=17&rft.spage=3821&rft.pages=3821-&rft.issn=1420-3049&rft.eissn=1420-3049&rft_id=info:doi/10.3390/molecules25173821&rft_dat=%3Cproquest_doaj_%3E2437405761%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c493t-7cabf3bf94ebf82d21696f0a5b8f62612da8475930270d520fb5daea4bce24a83%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2437643829&rft_id=info:pmid/32842645&rfr_iscdi=true