Frontiers in Anti-Infective Drug Discovery

Volume: 8

Drug Discovery Strategies Against Emerging Coronaviruses: A Global Threat

Author(s): Paulo Fernando da Silva Santos-Junior, Igor Jose dos Santos Nascimento, Thiago Mendonca de Aquino, Joao Xavier de Araujo-Junior and Edeildo Ferreira da Silva-Junior

Pp: 35-90 (56)

DOI: 10.2174/9789811412387120080004

* (Excluding Mailing and Handling)

Abstract

After the discovery of the infectious bronchitis virus (IBV) in 1932, Coronaviridae emerged as a family of viruses constituted of a positive-sense singlestranded RNA ((+)ssRNA) genome. Recently, the Coronavirus disease-2019 (COVID- 19), which is caused by a new virus called SARS-CoV-2 (provisionally titled 2019- nCoV), was declared pandemic since it reached global levels of infection. In comparison, this disease spread globally more quickly than previously reported SARS and MERS-CoV outbreaks. The impacts on global health systems (as well as the world economy, estimated to cost US$ 1 trillion) highlighted the urgent need to search for efficient pharmacotherapy targeting potential macromolecules from SARS-CoV-2 since there are no licensed vaccines or approved drugs until today. In this chapter, we will demonstrate all strategies that have been used to discover and design bioactive molecules against this viral infection, compiling from classical to computer-aided drug design, including also the drug repurposing. This last, it is based on analogs produced for past outbreaks related to SARS- and MERS-CoV. Finally, we aim to provide valuable information that could be applied for designing new safe, low cost, and selective lead-compounds against these emerging viruses.


Keywords: Coronaviruses, Drug Design, MERS-CoV, SARS-CoV, SARS-CoV- 2, HCoV.

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      • 15. middleware::check_user_access:114
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      • 14. app/Models/Subject.php:238
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      • 16. app/Models/Subject.php:255
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      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1465
      • 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
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      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1478
      • 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
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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 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 j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51727266 and j.to_ip >=51727266 )) and ((j.from_date <= 1740344794 and j.to_date >= 1740344794 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 14064) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51727266 and j.to_ip >=51727266 )) and ((j.from_date <= 1740344794 and j.to_date >= 1740344794 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 14064) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51727266 and j.to_ip >=51727266 )) and ((j.from_date <= 1740344794 and j.to_date >= 1740344794 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 14064)
      550μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 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 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` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 2661 and `b`.`banner_from_date` <= 1740344794 and `b`.`banner_to_date` >= 1740344794 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.07msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 2661
      • 3: 1740344794
      • 4: 1740344794
      • 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='764551e0fdda9d346f61af16ddcd8803'
      240μsalphaeurekaselec_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\Keywords
    6Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        xsc0WgwlGt5sY4zpLcBAQtzppwiP1hrZI90jEzbY
        uc_cart_id
        764551e0fdda9d346f61af16ddcd8803
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/14064" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/14064
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:16 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        []
        
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Sun, 23 Feb 2025 21:06:34 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkFpWFRFSzJCMVVkUi9weUNoblB5MHc9PSIsInZhbHVlIjoiSWRkNEtVb3BrTXltdnY4K1c5REl4VWlCR2IweUtFSHBoZkxvME5lRDFITkUwV1E0cGxyTEFtV1EwclBqcXVGWVR5bmRkTjN4UytkSVlVTVRHc3ZIemYvL0tWSldLR0hUWG1sa0Z4ZFc3R2cyaTlRaWpjQm96TUtYdTlWTEpRMkwiLCJtYWMiOiI4NWU4YmIwOWU0OGFhNzViYTUyM2E0ZTZhYjI0ZDgyMTBjZTJmOTUzYzBlNjRjYmZjZDc4MWM3YTU3Mzc2YzRmIiwidGFnIjoiIn0%3D; expires=Wed, 26 Feb 2025 09:06:34 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IkFpWFRFSzJCMVVkUi9weUNoblB5MHc9PSIsInZhbHVlIjoiSWRkNEtVb3BrTXltdnY4K1c5REl4VWlCR2IweUtFSHBoZkxvME5lRDFITkUwV1E0cGxyTEFtV1EwclBqcXVGWVR5bmRkT" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImtTVGpWMEVDMFFiSDIxaFVmT0tLbHc9PSIsInZhbHVlIjoiZmhVZEtudGh1YnVEVlNDd0pKZ2VFTWs5Njk1RG43cFpzTm9zUW5FTkY0Y0VSTkNNZ29RUm9zcU5vTmpnaDFRSW5IOVRSVnhDRGhBTHhnN1g5UFUzQ2xuM0JDcTEyMTdFVzNMUXZZbVNuSEJTNjI5STdSSitNS3ZVYXA1b3NwbnAiLCJtYWMiOiI5YzViN2U1YjY4MGU4ZmE4ZjZjNWNmZWM1NjNjNjg4ZDYwZWMzNjQ3YWNjZGE4ZGU1MzAxMTUxNTVmZmY0NzAxIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6ImtTVGpWMEVDMFFiSDIxaFVmT0tLbHc9PSIsInZhbHVlIjoiZmhVZEtudGh1YnVEVlNDd0pKZ2VFTWs5Njk1RG43cFpzTm9zUW5FTkY0Y0VSTkNNZ29RUm9zcU5" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkFpWFRFSzJCMVVkUi9weUNoblB5MHc9PSIsInZhbHVlIjoiSWRkNEtVb3BrTXltdnY4K1c5REl4VWlCR2IweUtFSHBoZkxvME5lRDFITkUwV1E0cGxyTEFtV1EwclBqcXVGWVR5bmRkTjN4UytkSVlVTVRHc3ZIemYvL0tWSldLR0hUWG1sa0Z4ZFc3R2cyaTlRaWpjQm96TUtYdTlWTEpRMkwiLCJtYWMiOiI4NWU4YmIwOWU0OGFhNzViYTUyM2E0ZTZhYjI0ZDgyMTBjZTJmOTUzYzBlNjRjYmZjZDc4MWM3YTU3Mzc2YzRmIiwidGFnIjoiIn0%3D; expires=Wed, 26-Feb-2025 09:06:34 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IkFpWFRFSzJCMVVkUi9weUNoblB5MHc9PSIsInZhbHVlIjoiSWRkNEtVb3BrTXltdnY4K1c5REl4VWlCR2IweUtFSHBoZkxvME5lRDFITkUwV1E0cGxyTEFtV1EwclBqcXVGWVR5bmRkT" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImtTVGpWMEVDMFFiSDIxaFVmT0tLbHc9PSIsInZhbHVlIjoiZmhVZEtudGh1YnVEVlNDd0pKZ2VFTWs5Njk1RG43cFpzTm9zUW5FTkY0Y0VSTkNNZ29RUm9zcU5vTmpnaDFRSW5IOVRSVnhDRGhBTHhnN1g5UFUzQ2xuM0JDcTEyMTdFVzNMUXZZbVNuSEJTNjI5STdSSitNS3ZVYXA1b3NwbnAiLCJtYWMiOiI5YzViN2U1YjY4MGU4ZmE4ZjZjNWNmZWM1NjNjNjg4ZDYwZWMzNjQ3YWNjZGE4ZGU1MzAxMTUxNTVmZmY0NzAxIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6ImtTVGpWMEVDMFFiSDIxaFVmT0tLbHc9PSIsInZhbHVlIjoiZmhVZEtudGh1YnVEVlNDd0pKZ2VFTWs5Njk1RG43cFpzTm9zUW5FTkY0Y0VSTkNNZ29RUm9zcU5" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "xsc0WgwlGt5sY4zpLcBAQtzppwiP1hrZI90jEzbY" "uc_cart_id" => "764551e0fdda9d346f61af16ddcd8803" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/14064" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-23 21:06:34GET/chapter/14064112198