Identifying SARS-CoV-2 Drugs Binding to the Spike Fatty Acid Binding Pocket Using In Silico Docking and Molecular Dynamics
Drugs against novel targets are needed to treat COVID-19 patients, especially as SARS-CoV-2 is capable of rapid mutation. Structure-based de novo drug design and repurposing of drugs and natural products is a rational approach to discovering potentially effective therapies. These in silico simulatio...
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| Veröffentlicht in: | International journal of molecular sciences 2023-02, Vol.24 (4), p.4192 |
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| creator | Piplani, Sakshi Singh, Puneet Petrovsky, Nikolai Winkler, David A |
| description | Drugs against novel targets are needed to treat COVID-19 patients, especially as SARS-CoV-2 is capable of rapid mutation. Structure-based de novo drug design and repurposing of drugs and natural products is a rational approach to discovering potentially effective therapies. These in silico simulations can quickly identify existing drugs with known safety profiles that can be repurposed for COVID-19 treatment. Here, we employ the newly identified spike protein free fatty acid binding pocket structure to identify repurposing candidates as potential SARS-CoV-2 therapies. Using a validated docking and molecular dynamics protocol effective at identifying repurposing candidates inhibiting other SARS-CoV-2 molecular targets, this study provides novel insights into the SARS-CoV-2 spike protein and its potential regulation by endogenous hormones and drugs. Some of the predicted repurposing candidates have already been demonstrated experimentally to inhibit SARS-CoV-2 activity, but most of the candidate drugs have yet to be tested for activity against the virus. We also elucidated a rationale for the effects of steroid and sex hormones and some vitamins on SARS-CoV-2 infection and COVID-19 recovery. |
| doi_str_mv | 10.3390/ijms24044192 |
| format | Article |
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Structure-based de novo drug design and repurposing of drugs and natural products is a rational approach to discovering potentially effective therapies. These in silico simulations can quickly identify existing drugs with known safety profiles that can be repurposed for COVID-19 treatment. Here, we employ the newly identified spike protein free fatty acid binding pocket structure to identify repurposing candidates as potential SARS-CoV-2 therapies. Using a validated docking and molecular dynamics protocol effective at identifying repurposing candidates inhibiting other SARS-CoV-2 molecular targets, this study provides novel insights into the SARS-CoV-2 spike protein and its potential regulation by endogenous hormones and drugs. Some of the predicted repurposing candidates have already been demonstrated experimentally to inhibit SARS-CoV-2 activity, but most of the candidate drugs have yet to be tested for activity against the virus. 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We also elucidated a rationale for the effects of steroid and sex hormones and some vitamins on SARS-CoV-2 infection and COVID-19 recovery.</description><subject>Amino acids</subject><subject>Antiviral Agents - pharmacology</subject><subject>Binding</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>COVID-19 Drug Treatment</subject><subject>Drug development</subject><subject>Drug Repositioning - methods</subject><subject>Drugs</subject><subject>Endocrine disruptors</subject><subject>Fatty Acids</subject><subject>Health aspects</subject><subject>Hormones</subject><subject>Hormones, Sex</subject><subject>Humans</subject><subject>Molecular docking</subject><subject>Molecular Docking Simulation</subject><subject>Molecular dynamics</subject><subject>Molecular Dynamics Simulation</subject><subject>Mutation</subject><subject>Nandrolone</subject><subject>Natural products</subject><subject>Protein binding</subject><subject>Proteins</subject><subject>Psychotropic drugs</subject><subject>SARS-CoV-2</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Sex hormones</subject><subject>Spike protein</subject><subject>Vitamins</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptks9v0zAUxyMEYmNw44wsceFAhmM7dnxBKi2DSkMgyrharv3SuUvsYidI5a_H0UbpEPLB78fnfa33_IrieYXPKZX4jdv2iTDMWCXJg-K0YoSUGHPx8Mg-KZ6ktMWYUFLLx8UJ5Q2tOSanxa-lBT-4du_8Bq1mX1flPHwvCVrEcZPQO-ftlBgCGq4BrXbuBtCFHoY9mhlnD_kvwdzAgK7S5Cw9WrnOmYAWOTxFtLfoU-jAjJ2OaLH3uncmPS0etbpL8OzuPiuuLt5_m38sLz9_WM5nl6VhQg4l2IplgzeVXDPdmJYAt6KiXHJmDQGAlglLhBaMNqRp2Vq2DAwhuMZGSEvPire3urtx3YM1ud-oO7WLrtdxr4J26n7Gu2u1CT-VlJxjSbLAqzuBGH6MkAbVu2Sg67SHMCZFRJOHTDiuM_ryH3Qbxuhze5kSsma0rpq_1EZ3oJxvQ37XTKJqJur8jzXBOFPn_6HysZDHFzy0LsfvFby-LTAxpBShPfRYYTXtijrelYy_OJ7LAf6zHPQ3EzW4Kg</recordid><startdate>20230220</startdate><enddate>20230220</enddate><creator>Piplani, Sakshi</creator><creator>Singh, Puneet</creator><creator>Petrovsky, Nikolai</creator><creator>Winkler, David A</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>8G5</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>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1580-5245</orcidid><orcidid>https://orcid.org/0000-0002-7301-6076</orcidid></search><sort><creationdate>20230220</creationdate><title>Identifying SARS-CoV-2 Drugs Binding to the Spike Fatty Acid Binding Pocket Using In Silico Docking and Molecular Dynamics</title><author>Piplani, Sakshi ; 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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Amino acids Antiviral Agents - pharmacology Binding Coronaviruses COVID-19 COVID-19 Drug Treatment Drug development Drug Repositioning - methods Drugs Endocrine disruptors Fatty Acids Health aspects Hormones Hormones, Sex Humans Molecular docking Molecular Docking Simulation Molecular dynamics Molecular Dynamics Simulation Mutation Nandrolone Natural products Protein binding Proteins Psychotropic drugs SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Sex hormones Spike protein Vitamins |
| title | Identifying SARS-CoV-2 Drugs Binding to the Spike Fatty Acid Binding Pocket Using In Silico Docking and Molecular Dynamics |
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