Derivatization and combination therapy of current COVID-19 therapeutic agents: a review of mechanistic pathways, adverse effects, and binding sites
[Display omitted] •We summarized the mechanisms of action of 11 repurposed drugs for COVID-19 treatment.•We reviewed clinical trials performed on drugs to treat COVID-19 patients.•We proposed combination therapy using current COVID-19 repurposed drugs.•Repurposed drugs have side effects and could be...
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| Veröffentlicht in: | Drug discovery today 2020-10, Vol.25 (10), p.1822-1838 |
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| container_issue | 10 |
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| container_title | Drug discovery today |
| container_volume | 25 |
| creator | El Kantar, Sally Nehmeh, Bilal Saad, Philippe Mitri, Gabie Estephan, Celine Mroueh, Mohamad Akoury, Elias Taleb, Robin I. |
| description | [Display omitted]
•We summarized the mechanisms of action of 11 repurposed drugs for COVID-19 treatment.•We reviewed clinical trials performed on drugs to treat COVID-19 patients.•We proposed combination therapy using current COVID-19 repurposed drugs.•Repurposed drugs have side effects and could be ineffective when the virus mutates.•We proposed drug derivatives with potentially enhanced activity against COVID-19.
Current treatment of patients with coronavirus 2019 (COVID-19) involves repurposed drugs that inhibit viral infection by either binding to their respective targets or via modulating cellular signal transduction. However, there is still a great deal of efficacy enhancement through combination therapy and derivatization. Combination therapy should involve agents with significant activity and different mechanisms of action. The structural map of the interaction between a drug and its target protein will help guide drug discovery for devising safe and effective ways to treat COVID-19. Herein, we report numerous synthetic designs based on enhanced affinity to the viral carbohydrate-rich protein spikes and protein-binding sites of COVID-19.
We report the structural design of several analogs of current COVID-19 repurposed drugs. These analogs are designed to enhance the drug affinity to either the protein-binding sites or to the viral protein spikes. |
| doi_str_mv | 10.1016/j.drudis.2020.08.002 |
| format | Article |
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•We summarized the mechanisms of action of 11 repurposed drugs for COVID-19 treatment.•We reviewed clinical trials performed on drugs to treat COVID-19 patients.•We proposed combination therapy using current COVID-19 repurposed drugs.•Repurposed drugs have side effects and could be ineffective when the virus mutates.•We proposed drug derivatives with potentially enhanced activity against COVID-19.
Current treatment of patients with coronavirus 2019 (COVID-19) involves repurposed drugs that inhibit viral infection by either binding to their respective targets or via modulating cellular signal transduction. However, there is still a great deal of efficacy enhancement through combination therapy and derivatization. Combination therapy should involve agents with significant activity and different mechanisms of action. The structural map of the interaction between a drug and its target protein will help guide drug discovery for devising safe and effective ways to treat COVID-19. Herein, we report numerous synthetic designs based on enhanced affinity to the viral carbohydrate-rich protein spikes and protein-binding sites of COVID-19.
We report the structural design of several analogs of current COVID-19 repurposed drugs. These analogs are designed to enhance the drug affinity to either the protein-binding sites or to the viral protein spikes.</description><identifier>ISSN: 1359-6446</identifier><identifier>EISSN: 1878-5832</identifier><identifier>DOI: 10.1016/j.drudis.2020.08.002</identifier><identifier>PMID: 32801052</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Antiviral Agents - adverse effects ; Antiviral Agents - therapeutic use ; Binding Sites ; Clinical Trials as Topic ; COVID-19 - metabolism ; COVID-19 - mortality ; COVID-19 - virology ; COVID-19 Drug Treatment ; Drug Repositioning ; Drug Therapy, Combination ; Evidence-Based Medicine ; Host-Pathogen Interactions ; Humans ; Ligands ; Molecular Targeted Therapy ; Review ; SARS-CoV-2 - drug effects ; SARS-CoV-2 - metabolism ; SARS-CoV-2 - pathogenicity ; Signal Transduction - drug effects ; Treatment Outcome</subject><ispartof>Drug discovery today, 2020-10, Vol.25 (10), p.1822-1838</ispartof><rights>2020 Elsevier Ltd</rights><rights>Copyright © 2020 Elsevier Ltd. All rights reserved.</rights><rights>2020 Elsevier Ltd. All rights reserved. 2020 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-145a1100c9c97e4eef00777050cd1c275438bae9fc4a02dc4020f314bb6a9a5a3</citedby><cites>FETCH-LOGICAL-c463t-145a1100c9c97e4eef00777050cd1c275438bae9fc4a02dc4020f314bb6a9a5a3</cites><orcidid>0000-0003-0377-0644 ; 0000-0001-8033-6951 ; 0000-0001-5202-8935 ; 0000-0002-0111-8313 ; 0000-0001-5413-1696</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.drudis.2020.08.002$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,777,781,882,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32801052$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>El Kantar, Sally</creatorcontrib><creatorcontrib>Nehmeh, Bilal</creatorcontrib><creatorcontrib>Saad, Philippe</creatorcontrib><creatorcontrib>Mitri, Gabie</creatorcontrib><creatorcontrib>Estephan, Celine</creatorcontrib><creatorcontrib>Mroueh, Mohamad</creatorcontrib><creatorcontrib>Akoury, Elias</creatorcontrib><creatorcontrib>Taleb, Robin I.</creatorcontrib><title>Derivatization and combination therapy of current COVID-19 therapeutic agents: a review of mechanistic pathways, adverse effects, and binding sites</title><title>Drug discovery today</title><addtitle>Drug Discov Today</addtitle><description>[Display omitted]
•We summarized the mechanisms of action of 11 repurposed drugs for COVID-19 treatment.•We reviewed clinical trials performed on drugs to treat COVID-19 patients.•We proposed combination therapy using current COVID-19 repurposed drugs.•Repurposed drugs have side effects and could be ineffective when the virus mutates.•We proposed drug derivatives with potentially enhanced activity against COVID-19.
Current treatment of patients with coronavirus 2019 (COVID-19) involves repurposed drugs that inhibit viral infection by either binding to their respective targets or via modulating cellular signal transduction. However, there is still a great deal of efficacy enhancement through combination therapy and derivatization. Combination therapy should involve agents with significant activity and different mechanisms of action. The structural map of the interaction between a drug and its target protein will help guide drug discovery for devising safe and effective ways to treat COVID-19. Herein, we report numerous synthetic designs based on enhanced affinity to the viral carbohydrate-rich protein spikes and protein-binding sites of COVID-19.
We report the structural design of several analogs of current COVID-19 repurposed drugs. These analogs are designed to enhance the drug affinity to either the protein-binding sites or to the viral protein spikes.</description><subject>Animals</subject><subject>Antiviral Agents - adverse effects</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Binding Sites</subject><subject>Clinical Trials as Topic</subject><subject>COVID-19 - metabolism</subject><subject>COVID-19 - mortality</subject><subject>COVID-19 - virology</subject><subject>COVID-19 Drug Treatment</subject><subject>Drug Repositioning</subject><subject>Drug Therapy, Combination</subject><subject>Evidence-Based Medicine</subject><subject>Host-Pathogen Interactions</subject><subject>Humans</subject><subject>Ligands</subject><subject>Molecular Targeted Therapy</subject><subject>Review</subject><subject>SARS-CoV-2 - drug effects</subject><subject>SARS-CoV-2 - metabolism</subject><subject>SARS-CoV-2 - pathogenicity</subject><subject>Signal Transduction - drug effects</subject><subject>Treatment Outcome</subject><issn>1359-6446</issn><issn>1878-5832</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU1v1DAQjRCIfsA_QMhHDiQdO07icECqtgUqVeoFuFoTe7Lr1SZZ7GSr5W_0D9fRLqVcOFj-ePPmed5LknccMg68vFhn1k_WhUyAgAxUBiBeJKdcVSotVC5exnNe1GkpZXmSnIWwBuCiLsrXyUkuFHAoxGnycEXe7XB0v-Maeoa9ZWboGtcf7uOKPG73bGiZmbynfmSLu583VymvjxhNozMMlxEKnxgyTztH9zOhI7PC3oUZ3-K4usd9-MjQ7sgHYtS2ZMb5IUpGPev6JQtupPAmedXiJtDb436e_Phy_X3xLb29-3qzuLxNjSzzMeWyQM4BTG3qiiRRC1BVFRRgLDeiKmSuGqS6NRJBWCOjT23OZdOUWGOB-Xny-dB3OzUdWRMn8LjRW-869Hs9oNP_Ir1b6eWw05UUoqrL2ODDsYEffk0URt25YGizwZ6GKWghc1kVCtRcKg-lxg8heGqfZDjoOU-91oc89ZynBqVjnpH2_vkXn0h_Avw7A0WjovFeB-OoN2Sdj_ZqO7j_KzwCp3O25g</recordid><startdate>20201001</startdate><enddate>20201001</enddate><creator>El Kantar, Sally</creator><creator>Nehmeh, Bilal</creator><creator>Saad, Philippe</creator><creator>Mitri, Gabie</creator><creator>Estephan, Celine</creator><creator>Mroueh, Mohamad</creator><creator>Akoury, Elias</creator><creator>Taleb, Robin I.</creator><general>Elsevier Ltd</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><orcidid>https://orcid.org/0000-0003-0377-0644</orcidid><orcidid>https://orcid.org/0000-0001-8033-6951</orcidid><orcidid>https://orcid.org/0000-0001-5202-8935</orcidid><orcidid>https://orcid.org/0000-0002-0111-8313</orcidid><orcidid>https://orcid.org/0000-0001-5413-1696</orcidid></search><sort><creationdate>20201001</creationdate><title>Derivatization and combination therapy of current COVID-19 therapeutic agents: a review of mechanistic pathways, adverse effects, and binding sites</title><author>El Kantar, Sally ; Nehmeh, Bilal ; Saad, Philippe ; Mitri, Gabie ; Estephan, Celine ; Mroueh, Mohamad ; Akoury, Elias ; Taleb, Robin I.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-145a1100c9c97e4eef00777050cd1c275438bae9fc4a02dc4020f314bb6a9a5a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Antiviral Agents - adverse effects</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Binding Sites</topic><topic>Clinical Trials as Topic</topic><topic>COVID-19 - metabolism</topic><topic>COVID-19 - mortality</topic><topic>COVID-19 - virology</topic><topic>COVID-19 Drug Treatment</topic><topic>Drug Repositioning</topic><topic>Drug Therapy, Combination</topic><topic>Evidence-Based Medicine</topic><topic>Host-Pathogen Interactions</topic><topic>Humans</topic><topic>Ligands</topic><topic>Molecular Targeted Therapy</topic><topic>Review</topic><topic>SARS-CoV-2 - drug effects</topic><topic>SARS-CoV-2 - metabolism</topic><topic>SARS-CoV-2 - pathogenicity</topic><topic>Signal Transduction - drug effects</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>El Kantar, Sally</creatorcontrib><creatorcontrib>Nehmeh, Bilal</creatorcontrib><creatorcontrib>Saad, Philippe</creatorcontrib><creatorcontrib>Mitri, Gabie</creatorcontrib><creatorcontrib>Estephan, Celine</creatorcontrib><creatorcontrib>Mroueh, Mohamad</creatorcontrib><creatorcontrib>Akoury, Elias</creatorcontrib><creatorcontrib>Taleb, Robin I.</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>Drug discovery today</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>El Kantar, Sally</au><au>Nehmeh, Bilal</au><au>Saad, Philippe</au><au>Mitri, Gabie</au><au>Estephan, Celine</au><au>Mroueh, Mohamad</au><au>Akoury, Elias</au><au>Taleb, Robin I.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Derivatization and combination therapy of current COVID-19 therapeutic agents: a review of mechanistic pathways, adverse effects, and binding sites</atitle><jtitle>Drug discovery today</jtitle><addtitle>Drug Discov Today</addtitle><date>2020-10-01</date><risdate>2020</risdate><volume>25</volume><issue>10</issue><spage>1822</spage><epage>1838</epage><pages>1822-1838</pages><issn>1359-6446</issn><eissn>1878-5832</eissn><abstract>[Display omitted]
•We summarized the mechanisms of action of 11 repurposed drugs for COVID-19 treatment.•We reviewed clinical trials performed on drugs to treat COVID-19 patients.•We proposed combination therapy using current COVID-19 repurposed drugs.•Repurposed drugs have side effects and could be ineffective when the virus mutates.•We proposed drug derivatives with potentially enhanced activity against COVID-19.
Current treatment of patients with coronavirus 2019 (COVID-19) involves repurposed drugs that inhibit viral infection by either binding to their respective targets or via modulating cellular signal transduction. However, there is still a great deal of efficacy enhancement through combination therapy and derivatization. Combination therapy should involve agents with significant activity and different mechanisms of action. The structural map of the interaction between a drug and its target protein will help guide drug discovery for devising safe and effective ways to treat COVID-19. Herein, we report numerous synthetic designs based on enhanced affinity to the viral carbohydrate-rich protein spikes and protein-binding sites of COVID-19.
We report the structural design of several analogs of current COVID-19 repurposed drugs. These analogs are designed to enhance the drug affinity to either the protein-binding sites or to the viral protein spikes.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>32801052</pmid><doi>10.1016/j.drudis.2020.08.002</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0003-0377-0644</orcidid><orcidid>https://orcid.org/0000-0001-8033-6951</orcidid><orcidid>https://orcid.org/0000-0001-5202-8935</orcidid><orcidid>https://orcid.org/0000-0002-0111-8313</orcidid><orcidid>https://orcid.org/0000-0001-5413-1696</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1359-6446 |
| ispartof | Drug discovery today, 2020-10, Vol.25 (10), p.1822-1838 |
| issn | 1359-6446 1878-5832 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Antiviral Agents - adverse effects Antiviral Agents - therapeutic use Binding Sites Clinical Trials as Topic COVID-19 - metabolism COVID-19 - mortality COVID-19 - virology COVID-19 Drug Treatment Drug Repositioning Drug Therapy, Combination Evidence-Based Medicine Host-Pathogen Interactions Humans Ligands Molecular Targeted Therapy Review SARS-CoV-2 - drug effects SARS-CoV-2 - metabolism SARS-CoV-2 - pathogenicity Signal Transduction - drug effects Treatment Outcome |
| title | Derivatization and combination therapy of current COVID-19 therapeutic agents: a review of mechanistic pathways, adverse effects, and binding sites |
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