Phylogenetic Analysis and Structural Perspectives of RNA-Dependent RNA-Polymerase Inhibition from SARs-CoV-2 with Natural Products
Most recently, an outbreak of severe pneumonia caused by the infection of SARS-CoV-2, a novel coronavirus first identified in Wuhan, China, imposes serious threats to public health. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural protei...
Gespeichert in:
| Veröffentlicht in: | Interdisciplinary sciences : computational life sciences 2020-09, Vol.12 (3), p.335-348 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 348 |
|---|---|
| container_issue | 3 |
| container_start_page | 335 |
| container_title | Interdisciplinary sciences : computational life sciences |
| container_volume | 12 |
| creator | Khan, Abbas Khan, Mazhar Saleem, Shoaib Babar, Zainib Ali, Arif Khan, Abdul Aziz Sardar, Zain Hamayun, Fahad Ali, Syed Shujait Wei, Dong-Qing |
| description | Most recently, an outbreak of severe pneumonia caused by the infection of SARS-CoV-2, a novel coronavirus first identified in Wuhan, China, imposes serious threats to public health. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Therefore, the role and inhibition of nsp12 are indispensable. A cryo-EM structure of RdRp from SARs-CoV-2 was used to identify novel drugs from Northern South African medicinal compounds database (NANPDB) by using computational virtual screening and molecular docking approaches. Considering Remdesivir as the control, 42 compounds were shortlisted to have docking score better than Remdesivir. The top 5 hits were validated by using molecular dynamics simulation approach and free energy calculations possess strong inhibitory properties than the Remdesivir. Thus, this study paved a way for designing novel drugs by decoding the architecture of an important enzyme and its inhibition with compounds from natural resources. This disclosing of necessary knowledge regarding the screening and the identification of top hits could help to design effective therapeutic candidates against the coronaviruses and design robust preventive measurements.
Graphic abstract |
| doi_str_mv | 10.1007/s12539-020-00381-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7332347</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2431014327</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-428485f6a8cd3b9ae50e6e3b2a204f10abe473e8da5922b6101ae9e9c0337e0b3</originalsourceid><addsrcrecordid>eNp9kUtvEzEUhS1ERUvoH2CBLLE22L6e1wYpSnlUqkrUQreWZ-ZO4mpiB9tTlC2_HLdJC2xY2dY99ztHPoS8Fvyd4Lx6H4UsoGFccsY51II1z8iJqMuKCVXK5_neCGCyKsQxeRnjLeelqoG_IMcgS1HVRXFCfi3Xu9Gv0GGyHZ07M-6ijdS4nl6nMHVpCmakSwxxi12ydxipH-jV5Zyd4RZdjy49vJZ-3G0wmIj03K1ta5P1jg7Bb-j1_Cqyhb9hkv60aU0vzQEafJ8N4ityNJgx4unhnJHvnz5-W3xhF18_ny_mF6xTlUpMyVrVxVCauuuhbQwWHEuEVhrJ1SC4aVFVgHVvikbKthRcGGyw6ThAhbyFGfmw526ndoN9l6PnGHob7MaEnfbG6n8nzq71yt_pCkBCZs_I2wMg-B8TxqRv_RTyl0UtFWQ_BfJeJfeqLvgYAw5PDoLr-970vjede9MPvekmL735O9vTymNRWQB7Qcwjt8Lwx_s_2N8YsaV8</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2431014327</pqid></control><display><type>article</type><title>Phylogenetic Analysis and Structural Perspectives of RNA-Dependent RNA-Polymerase Inhibition from SARs-CoV-2 with Natural Products</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Khan, Abbas ; Khan, Mazhar ; Saleem, Shoaib ; Babar, Zainib ; Ali, Arif ; Khan, Abdul Aziz ; Sardar, Zain ; Hamayun, Fahad ; Ali, Syed Shujait ; Wei, Dong-Qing</creator><creatorcontrib>Khan, Abbas ; Khan, Mazhar ; Saleem, Shoaib ; Babar, Zainib ; Ali, Arif ; Khan, Abdul Aziz ; Sardar, Zain ; Hamayun, Fahad ; Ali, Syed Shujait ; Wei, Dong-Qing</creatorcontrib><description>Most recently, an outbreak of severe pneumonia caused by the infection of SARS-CoV-2, a novel coronavirus first identified in Wuhan, China, imposes serious threats to public health. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Therefore, the role and inhibition of nsp12 are indispensable. A cryo-EM structure of RdRp from SARs-CoV-2 was used to identify novel drugs from Northern South African medicinal compounds database (NANPDB) by using computational virtual screening and molecular docking approaches. Considering Remdesivir as the control, 42 compounds were shortlisted to have docking score better than Remdesivir. The top 5 hits were validated by using molecular dynamics simulation approach and free energy calculations possess strong inhibitory properties than the Remdesivir. Thus, this study paved a way for designing novel drugs by decoding the architecture of an important enzyme and its inhibition with compounds from natural resources. This disclosing of necessary knowledge regarding the screening and the identification of top hits could help to design effective therapeutic candidates against the coronaviruses and design robust preventive measurements.
Graphic abstract</description><identifier>ISSN: 1913-2751</identifier><identifier>EISSN: 1867-1462</identifier><identifier>DOI: 10.1007/s12539-020-00381-9</identifier><identifier>PMID: 32617855</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adenosine Monophosphate - analogs & derivatives ; Adenosine Monophosphate - chemistry ; Adenosine Monophosphate - pharmacology ; Alanine - analogs & derivatives ; Alanine - chemistry ; Alanine - pharmacology ; Antiviral Agents - chemistry ; Antiviral Agents - pharmacology ; Betacoronavirus - drug effects ; Betacoronavirus - enzymology ; Betacoronavirus - genetics ; Biological Products - chemistry ; Biological Products - pharmacology ; Biomedical and Life Sciences ; Catalytic Domain - genetics ; Computational Biology/Bioinformatics ; Computational Science and Engineering ; Computer Appl. in Life Sciences ; Computer applications ; Computer Simulation ; Coronaviridae ; Coronavirus Infections - epidemiology ; Coronavirus Infections - virology ; Coronavirus RNA-Dependent RNA Polymerase ; Coronaviruses ; COVID-19 ; Databases, Pharmaceutical ; DNA-directed RNA polymerase ; Drug Evaluation, Preclinical ; Drugs ; Free energy ; Genome, Viral ; Genomes ; Health Sciences ; Host Microbial Interactions - drug effects ; Humans ; Life Sciences ; Ligands ; Mathematical and Computational Physics ; Medicine ; Molecular docking ; Molecular Docking Simulation ; Molecular dynamics ; Natural products ; Natural resources ; Original ; Original Research Article ; Pandemics ; Phylogeny ; Pneumonia, Viral - epidemiology ; Pneumonia, Viral - virology ; Public health ; Ribonucleic acid ; RNA ; RNA-Dependent RNA Polymerase - antagonists & inhibitors ; RNA-Dependent RNA Polymerase - chemistry ; RNA-Dependent RNA Polymerase - genetics ; SARS-CoV-2 ; Screening ; Severe acute respiratory syndrome coronavirus 2 ; Statistics for Life Sciences ; Structural proteins ; Theoretical ; Theoretical and Computational Chemistry ; Transcription ; Viral diseases ; Viral Nonstructural Proteins - antagonists & inhibitors ; Viral Nonstructural Proteins - chemistry ; Viral Nonstructural Proteins - genetics</subject><ispartof>Interdisciplinary sciences : computational life sciences, 2020-09, Vol.12 (3), p.335-348</ispartof><rights>International Association of Scientists in the Interdisciplinary Areas 2020</rights><rights>International Association of Scientists in the Interdisciplinary Areas 2020.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-428485f6a8cd3b9ae50e6e3b2a204f10abe473e8da5922b6101ae9e9c0337e0b3</citedby><cites>FETCH-LOGICAL-c474t-428485f6a8cd3b9ae50e6e3b2a204f10abe473e8da5922b6101ae9e9c0337e0b3</cites><orcidid>0000-0003-4200-7502</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/s12539-020-00381-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12539-020-00381-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32617855$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Khan, Abbas</creatorcontrib><creatorcontrib>Khan, Mazhar</creatorcontrib><creatorcontrib>Saleem, Shoaib</creatorcontrib><creatorcontrib>Babar, Zainib</creatorcontrib><creatorcontrib>Ali, Arif</creatorcontrib><creatorcontrib>Khan, Abdul Aziz</creatorcontrib><creatorcontrib>Sardar, Zain</creatorcontrib><creatorcontrib>Hamayun, Fahad</creatorcontrib><creatorcontrib>Ali, Syed Shujait</creatorcontrib><creatorcontrib>Wei, Dong-Qing</creatorcontrib><title>Phylogenetic Analysis and Structural Perspectives of RNA-Dependent RNA-Polymerase Inhibition from SARs-CoV-2 with Natural Products</title><title>Interdisciplinary sciences : computational life sciences</title><addtitle>Interdiscip Sci Comput Life Sci</addtitle><addtitle>Interdiscip Sci</addtitle><description>Most recently, an outbreak of severe pneumonia caused by the infection of SARS-CoV-2, a novel coronavirus first identified in Wuhan, China, imposes serious threats to public health. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Therefore, the role and inhibition of nsp12 are indispensable. A cryo-EM structure of RdRp from SARs-CoV-2 was used to identify novel drugs from Northern South African medicinal compounds database (NANPDB) by using computational virtual screening and molecular docking approaches. Considering Remdesivir as the control, 42 compounds were shortlisted to have docking score better than Remdesivir. The top 5 hits were validated by using molecular dynamics simulation approach and free energy calculations possess strong inhibitory properties than the Remdesivir. Thus, this study paved a way for designing novel drugs by decoding the architecture of an important enzyme and its inhibition with compounds from natural resources. This disclosing of necessary knowledge regarding the screening and the identification of top hits could help to design effective therapeutic candidates against the coronaviruses and design robust preventive measurements.
Graphic abstract</description><subject>Adenosine Monophosphate - analogs & derivatives</subject><subject>Adenosine Monophosphate - chemistry</subject><subject>Adenosine Monophosphate - pharmacology</subject><subject>Alanine - analogs & derivatives</subject><subject>Alanine - chemistry</subject><subject>Alanine - pharmacology</subject><subject>Antiviral Agents - chemistry</subject><subject>Antiviral Agents - pharmacology</subject><subject>Betacoronavirus - drug effects</subject><subject>Betacoronavirus - enzymology</subject><subject>Betacoronavirus - genetics</subject><subject>Biological Products - chemistry</subject><subject>Biological Products - pharmacology</subject><subject>Biomedical and Life Sciences</subject><subject>Catalytic Domain - genetics</subject><subject>Computational Biology/Bioinformatics</subject><subject>Computational Science and Engineering</subject><subject>Computer Appl. in Life Sciences</subject><subject>Computer applications</subject><subject>Computer Simulation</subject><subject>Coronaviridae</subject><subject>Coronavirus Infections - epidemiology</subject><subject>Coronavirus Infections - virology</subject><subject>Coronavirus RNA-Dependent RNA Polymerase</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>Databases, Pharmaceutical</subject><subject>DNA-directed RNA polymerase</subject><subject>Drug Evaluation, Preclinical</subject><subject>Drugs</subject><subject>Free energy</subject><subject>Genome, Viral</subject><subject>Genomes</subject><subject>Health Sciences</subject><subject>Host Microbial Interactions - drug effects</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Ligands</subject><subject>Mathematical and Computational Physics</subject><subject>Medicine</subject><subject>Molecular docking</subject><subject>Molecular Docking Simulation</subject><subject>Molecular dynamics</subject><subject>Natural products</subject><subject>Natural resources</subject><subject>Original</subject><subject>Original Research Article</subject><subject>Pandemics</subject><subject>Phylogeny</subject><subject>Pneumonia, Viral - epidemiology</subject><subject>Pneumonia, Viral - virology</subject><subject>Public health</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA-Dependent RNA Polymerase - antagonists & inhibitors</subject><subject>RNA-Dependent RNA Polymerase - chemistry</subject><subject>RNA-Dependent RNA Polymerase - genetics</subject><subject>SARS-CoV-2</subject><subject>Screening</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Statistics for Life Sciences</subject><subject>Structural proteins</subject><subject>Theoretical</subject><subject>Theoretical and Computational Chemistry</subject><subject>Transcription</subject><subject>Viral diseases</subject><subject>Viral Nonstructural Proteins - antagonists & inhibitors</subject><subject>Viral Nonstructural Proteins - chemistry</subject><subject>Viral Nonstructural Proteins - genetics</subject><issn>1913-2751</issn><issn>1867-1462</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtvEzEUhS1ERUvoH2CBLLE22L6e1wYpSnlUqkrUQreWZ-ZO4mpiB9tTlC2_HLdJC2xY2dY99ztHPoS8Fvyd4Lx6H4UsoGFccsY51II1z8iJqMuKCVXK5_neCGCyKsQxeRnjLeelqoG_IMcgS1HVRXFCfi3Xu9Gv0GGyHZ07M-6ijdS4nl6nMHVpCmakSwxxi12ydxipH-jV5Zyd4RZdjy49vJZ-3G0wmIj03K1ta5P1jg7Bb-j1_Cqyhb9hkv60aU0vzQEafJ8N4ityNJgx4unhnJHvnz5-W3xhF18_ny_mF6xTlUpMyVrVxVCauuuhbQwWHEuEVhrJ1SC4aVFVgHVvikbKthRcGGyw6ThAhbyFGfmw526ndoN9l6PnGHob7MaEnfbG6n8nzq71yt_pCkBCZs_I2wMg-B8TxqRv_RTyl0UtFWQ_BfJeJfeqLvgYAw5PDoLr-970vjede9MPvekmL735O9vTymNRWQB7Qcwjt8Lwx_s_2N8YsaV8</recordid><startdate>20200901</startdate><enddate>20200901</enddate><creator>Khan, Abbas</creator><creator>Khan, Mazhar</creator><creator>Saleem, Shoaib</creator><creator>Babar, Zainib</creator><creator>Ali, Arif</creator><creator>Khan, Abdul Aziz</creator><creator>Sardar, Zain</creator><creator>Hamayun, Fahad</creator><creator>Ali, Syed Shujait</creator><creator>Wei, Dong-Qing</creator><general>Springer Berlin Heidelberg</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>7QO</scope><scope>7SC</scope><scope>8FD</scope><scope>FR3</scope><scope>JQ2</scope><scope>K9.</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4200-7502</orcidid></search><sort><creationdate>20200901</creationdate><title>Phylogenetic Analysis and Structural Perspectives of RNA-Dependent RNA-Polymerase Inhibition from SARs-CoV-2 with Natural Products</title><author>Khan, Abbas ; Khan, Mazhar ; Saleem, Shoaib ; Babar, Zainib ; Ali, Arif ; Khan, Abdul Aziz ; Sardar, Zain ; Hamayun, Fahad ; Ali, Syed Shujait ; Wei, Dong-Qing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-428485f6a8cd3b9ae50e6e3b2a204f10abe473e8da5922b6101ae9e9c0337e0b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adenosine Monophosphate - analogs & derivatives</topic><topic>Adenosine Monophosphate - chemistry</topic><topic>Adenosine Monophosphate - pharmacology</topic><topic>Alanine - analogs & derivatives</topic><topic>Alanine - chemistry</topic><topic>Alanine - pharmacology</topic><topic>Antiviral Agents - chemistry</topic><topic>Antiviral Agents - pharmacology</topic><topic>Betacoronavirus - drug effects</topic><topic>Betacoronavirus - enzymology</topic><topic>Betacoronavirus - genetics</topic><topic>Biological Products - chemistry</topic><topic>Biological Products - pharmacology</topic><topic>Biomedical and Life Sciences</topic><topic>Catalytic Domain - genetics</topic><topic>Computational Biology/Bioinformatics</topic><topic>Computational Science and Engineering</topic><topic>Computer Appl. in Life Sciences</topic><topic>Computer applications</topic><topic>Computer Simulation</topic><topic>Coronaviridae</topic><topic>Coronavirus Infections - epidemiology</topic><topic>Coronavirus Infections - virology</topic><topic>Coronavirus RNA-Dependent RNA Polymerase</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>Databases, Pharmaceutical</topic><topic>DNA-directed RNA polymerase</topic><topic>Drug Evaluation, Preclinical</topic><topic>Drugs</topic><topic>Free energy</topic><topic>Genome, Viral</topic><topic>Genomes</topic><topic>Health Sciences</topic><topic>Host Microbial Interactions - drug effects</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Ligands</topic><topic>Mathematical and Computational Physics</topic><topic>Medicine</topic><topic>Molecular docking</topic><topic>Molecular Docking Simulation</topic><topic>Molecular dynamics</topic><topic>Natural products</topic><topic>Natural resources</topic><topic>Original</topic><topic>Original Research Article</topic><topic>Pandemics</topic><topic>Phylogeny</topic><topic>Pneumonia, Viral - epidemiology</topic><topic>Pneumonia, Viral - virology</topic><topic>Public health</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA-Dependent RNA Polymerase - antagonists & inhibitors</topic><topic>RNA-Dependent RNA Polymerase - chemistry</topic><topic>RNA-Dependent RNA Polymerase - genetics</topic><topic>SARS-CoV-2</topic><topic>Screening</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Statistics for Life Sciences</topic><topic>Structural proteins</topic><topic>Theoretical</topic><topic>Theoretical and Computational Chemistry</topic><topic>Transcription</topic><topic>Viral diseases</topic><topic>Viral Nonstructural Proteins - antagonists & inhibitors</topic><topic>Viral Nonstructural Proteins - chemistry</topic><topic>Viral Nonstructural Proteins - genetics</topic><toplevel>online_resources</toplevel><creatorcontrib>Khan, Abbas</creatorcontrib><creatorcontrib>Khan, Mazhar</creatorcontrib><creatorcontrib>Saleem, Shoaib</creatorcontrib><creatorcontrib>Babar, Zainib</creatorcontrib><creatorcontrib>Ali, Arif</creatorcontrib><creatorcontrib>Khan, Abdul Aziz</creatorcontrib><creatorcontrib>Sardar, Zain</creatorcontrib><creatorcontrib>Hamayun, Fahad</creatorcontrib><creatorcontrib>Ali, Syed Shujait</creatorcontrib><creatorcontrib>Wei, Dong-Qing</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Interdisciplinary sciences : computational life sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khan, Abbas</au><au>Khan, Mazhar</au><au>Saleem, Shoaib</au><au>Babar, Zainib</au><au>Ali, Arif</au><au>Khan, Abdul Aziz</au><au>Sardar, Zain</au><au>Hamayun, Fahad</au><au>Ali, Syed Shujait</au><au>Wei, Dong-Qing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phylogenetic Analysis and Structural Perspectives of RNA-Dependent RNA-Polymerase Inhibition from SARs-CoV-2 with Natural Products</atitle><jtitle>Interdisciplinary sciences : computational life sciences</jtitle><stitle>Interdiscip Sci Comput Life Sci</stitle><addtitle>Interdiscip Sci</addtitle><date>2020-09-01</date><risdate>2020</risdate><volume>12</volume><issue>3</issue><spage>335</spage><epage>348</epage><pages>335-348</pages><issn>1913-2751</issn><eissn>1867-1462</eissn><abstract>Most recently, an outbreak of severe pneumonia caused by the infection of SARS-CoV-2, a novel coronavirus first identified in Wuhan, China, imposes serious threats to public health. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Therefore, the role and inhibition of nsp12 are indispensable. A cryo-EM structure of RdRp from SARs-CoV-2 was used to identify novel drugs from Northern South African medicinal compounds database (NANPDB) by using computational virtual screening and molecular docking approaches. Considering Remdesivir as the control, 42 compounds were shortlisted to have docking score better than Remdesivir. The top 5 hits were validated by using molecular dynamics simulation approach and free energy calculations possess strong inhibitory properties than the Remdesivir. Thus, this study paved a way for designing novel drugs by decoding the architecture of an important enzyme and its inhibition with compounds from natural resources. This disclosing of necessary knowledge regarding the screening and the identification of top hits could help to design effective therapeutic candidates against the coronaviruses and design robust preventive measurements.
Graphic abstract</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>32617855</pmid><doi>10.1007/s12539-020-00381-9</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-4200-7502</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1913-2751 |
| ispartof | Interdisciplinary sciences : computational life sciences, 2020-09, Vol.12 (3), p.335-348 |
| issn | 1913-2751 1867-1462 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7332347 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Adenosine Monophosphate - analogs & derivatives Adenosine Monophosphate - chemistry Adenosine Monophosphate - pharmacology Alanine - analogs & derivatives Alanine - chemistry Alanine - pharmacology Antiviral Agents - chemistry Antiviral Agents - pharmacology Betacoronavirus - drug effects Betacoronavirus - enzymology Betacoronavirus - genetics Biological Products - chemistry Biological Products - pharmacology Biomedical and Life Sciences Catalytic Domain - genetics Computational Biology/Bioinformatics Computational Science and Engineering Computer Appl. in Life Sciences Computer applications Computer Simulation Coronaviridae Coronavirus Infections - epidemiology Coronavirus Infections - virology Coronavirus RNA-Dependent RNA Polymerase Coronaviruses COVID-19 Databases, Pharmaceutical DNA-directed RNA polymerase Drug Evaluation, Preclinical Drugs Free energy Genome, Viral Genomes Health Sciences Host Microbial Interactions - drug effects Humans Life Sciences Ligands Mathematical and Computational Physics Medicine Molecular docking Molecular Docking Simulation Molecular dynamics Natural products Natural resources Original Original Research Article Pandemics Phylogeny Pneumonia, Viral - epidemiology Pneumonia, Viral - virology Public health Ribonucleic acid RNA RNA-Dependent RNA Polymerase - antagonists & inhibitors RNA-Dependent RNA Polymerase - chemistry RNA-Dependent RNA Polymerase - genetics SARS-CoV-2 Screening Severe acute respiratory syndrome coronavirus 2 Statistics for Life Sciences Structural proteins Theoretical Theoretical and Computational Chemistry Transcription Viral diseases Viral Nonstructural Proteins - antagonists & inhibitors Viral Nonstructural Proteins - chemistry Viral Nonstructural Proteins - genetics |
| title | Phylogenetic Analysis and Structural Perspectives of RNA-Dependent RNA-Polymerase Inhibition from SARs-CoV-2 with Natural Products |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T20%3A46%3A02IST&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=Phylogenetic%20Analysis%20and%20Structural%20Perspectives%20of%20RNA-Dependent%20RNA-Polymerase%20Inhibition%20from%20SARs-CoV-2%20with%20Natural%20Products&rft.jtitle=Interdisciplinary%20sciences%20:%20computational%20life%20sciences&rft.au=Khan,%20Abbas&rft.date=2020-09-01&rft.volume=12&rft.issue=3&rft.spage=335&rft.epage=348&rft.pages=335-348&rft.issn=1913-2751&rft.eissn=1867-1462&rft_id=info:doi/10.1007/s12539-020-00381-9&rft_dat=%3Cproquest_pubme%3E2431014327%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=2431014327&rft_id=info:pmid/32617855&rfr_iscdi=true |