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Coronaviruses

Editor-in-Chief

ISSN (Print): 2666-7967
ISSN (Online): 2666-7975

Research Article

Virtual Screening of Potential Therapeutic Inhibitors Against Spike, Helicase, and Polymerase of SARS-CoV-2 (COVID-19)

Author(s): Ayesha Tazeen, Farah Deeba, Aftab Alam, Rafat Ali, Romana Ishrat, Anwar Ahmed, Sher Ali and Shama Parveen*

Volume 2, Issue 1, 2021

Published on: 26 August, 2020

Page: [89 - 105] Pages: 17

DOI: 10.2174/2666796701999200826114306

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected around 13 million people and has caused more than 5.7 lakh deaths worldwide since December 2019. In the absence of FDA approved drugs for its treatment, only symptomatic management is done.

Methods: We attempted to uncover potential therapeutic targets of spike, helicase, and RNA dependent RNA polymerase (RdRp) proteins of the SARS-CoV-2 employing a computational approach. The PDB structure of spike and RdRp and predicted structure of helicase proteins were docked with 100 approved anti-viral drugs, natural compounds, and some other chemical compounds.

Results: The anti-SARS ligands EK1 and CID 23631927, and NCGC00029283 are potential entry inhibitors as they showed affinity with immunogenic Receptor Binding Domain (RBD) of the spike protein. This RBD interacts with Angiotensin Converting Enzyme (ACE2) receptor, facilitating the entry of virion in the host cells. The FDA approved drugs, including Nelfinavir, Saquinavir, Tipranavir, Setrobuvir, Indinavir, and Atazanavir, showed potential inhibitory activity against targeted domains and thus, may act as entry or replication inhibitor or both. Furthermore, several anti-HCoV natural compounds, including Amentoflavone, Rutin, and Tannin, are also potential entry and replication inhibitors as they showed affinity with RBD, P-loop containing nucleoside triphosphate hydrolase, and the catalytic domain of the respective protein. Dithymoquinone showed significant inhibitory potential against the fusion peptide of S2 domain. Importantly, Tannin, Dithymoquinone, and Rutin can be extracted from Nigella sativa seeds and thus, may prove to be one of the most potential anti-SARS-CoV-2 inhibitors.

Conclusion: Several potential ligands were identified with already known anti-HCoVs activities. Furthermore, as this study showed that some of the ligands acted as both entry and replication inhibitors against SARS-CoV-2, it is envisaged that a combination of either inhibitor with a dual mode of action would prove to be a much desired therapeutic option against this viral infection.

Keywords: SARS-CoV-2, spike, helicase, RdRp, virtual screening, potential inhibitors, drug repurposing, natural compounds


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      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
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      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
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      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 190 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      4.77msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 190 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      2.26msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 109494 limit 1
      730μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 109494
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 109494 and content_type = 'article' order by status desc limit 1
      1.47msalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid article_nid,a.title article_title,j.title journal_title from content_by_diseases cd inner join article a on a.article_id=cd.content_id inner join journal j on j.journal_id=a.journal_id where cd.pid = 622 and cd.sub_disease_id = 623 and content_id!=109494 and cd.content_type = 'article' order by rand() limit 20
      8.26msalphaeurekaselec_live_10_06_2022Article.php#769
      Backtrace
      • 11. app/Models/Article.php:769
      • 12. app/Http/Controllers/ArticleController.php:2098
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 185335 limit 1
      230μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 185335
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      230μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'COVID' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      280μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: COVID
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '109494' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      400μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '10381' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      320μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '3027' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      350μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '89' and is_uploaded = 1 and issue_id = 10381 order by cast(first_page as SIGNED) desc limit 1
      570μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 89
      Backtrace
      • 14. app/Models/Article.php:1819
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '105' and is_uploaded = 1 and issue_id = 10381 order by cast(first_page as SIGNED) asc limit 1
      530μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 105
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      190μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      240μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 109494 limit 1
      2.38msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 109494
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 190 and `b`.`banner_from_date` <= 1740347609 and `b`.`banner_to_date` >= 1740347609 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.14msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 190
      • 3: 1740347609
      • 4: 1740347609
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 190 and `b`.`banner_from_date` <= 1740347609 and `b`.`banner_to_date` >= 1740347609 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.14msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 190
      • 3: 1740347609
      • 4: 1740347609
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='66845600ea6b88f118b4e942afc198ca'
      250μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        h8gXxGLQcLaksteDGigEsuPg9ewVZVkC3slMiL8E
        uc_cart_id
        66845600ea6b88f118b4e942afc198ca
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        array:1 [ "url" => "http://alpha.eurekaselect.com/article/109494" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
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        []
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        200
        
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-23 21:53:29GET/article/109494413341