Frontiers in Medicinal Chemistry

Volume: 6

The Efficacy of Viral Capsid Inhibitors in Human Enterovirus Infection and Associated Diseases

Author(s): Shin-Ru Shih, Gary Brewer, Peng-Nien Huang, Kuo-Feng Weng, Chin Li, Hongtao Wang, Tzu-Chun Chen and Mei-Ling Li

Pp: 22-40 (19)

DOI: 10.2174/9781608054640113060004

* (Excluding Mailing and Handling)

Abstract

Enteroviruses are members of picornavirus family which causes diverse and severe diseases in humans and animals. Clinical manifestations of enterovirus infections include fever, hand, foot, and mouth disease, and herpangina. Enteroviruses also cause potentially severe and life-threatening infections such as meningitis, encephalitis, myocarditis, polio-like syndrome, and neonatal sepsis. With the emergence of enterovirus all over the world as the major causative agent of HFMD fatalities in recent years and in the absence of any effective anti-enteroviral therapy, there is clearly a need to find a specific antiviral therapy. Steps such as viral attachment, uncoating, viral RNA replication, and protein synthesis in the replication cycle can serve as potential targets for antiviral agents. Agents targeted at viral protein 1 (VP1), a relatively conserved capsid structure mediating viral adsorption and uncoating process, is of great potential to be anti-enterovirus drugs.

Recently, considerable efforts have been made in the development of antiviral compounds targeting the capsid protein of enterovirus. This review summarizes the development of small molecules targeting enteroviral capsid protein as effective antiviral therapy.


Keywords: Enterovirus, capsid protein, antiviral therapy.

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      • 15. middleware::check_user_access:114
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      • 19. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
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      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
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      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
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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
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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
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      Backtrace
      • 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 <= 51592399 and j.to_ip >=51592399 )) and ((j.from_date <= 1739834413 and j.to_date >= 1739834413 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 4710) 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 <= 51592399 and j.to_ip >=51592399 )) and ((j.from_date <= 1739834413 and j.to_date >= 1739834413 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 4710) 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 <= 51592399 and j.to_ip >=51592399 )) and ((j.from_date <= 1739834413 and j.to_date >= 1739834413 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 4710)
      800μsalphaeurekaselec_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` = 1146 and `b`.`banner_from_date` <= 1739834413 and `b`.`banner_to_date` >= 1739834413 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.47msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 1146
      • 3: 1739834413
      • 4: 1739834413
      • 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='cbfd2aa8bfd31ffbf9b56a1a18c48bbd'
      260μsalphaeurekaselec_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
    3Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        Bs9X3CK9J8kh5UVcKY35yw5wQemLBepxapqwedXS
        uc_cart_id
        cbfd2aa8bfd31ffbf9b56a1a18c48bbd
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/4710" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/4710
        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:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6ImVydzZvRlBqbTBndlF6eVRuWmVMMlE9PSIsInZhbHVlIjoiVWw3QXpXd21mTXMxRnpNM1lXUmFRVThHZkxjbFZvenZ4Z0toMWtwNUQ2VT0iLCJtYWMiOiIxZjA5MzA0MWNmMzZkZThhZjI1YjUzMDIwOTUxODBiMjViMjdkNjM4OGJmMTgyZDA1ZTYyZTI5OGE0NGY5MTAxIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6ImVydzZvRlBqbTBndlF6eVRuWmVMMlE9PSIsInZhbHVlIjoiVWw3QXpXd21mTXMxRnpNM1lXUmFRVThHZkxjbFZvenZ4Z0toMWtwNUQ2VT0iLCJtYWMiOiIxZjA5MzA0MWNmMzZk" ] "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
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        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 => "Mon, 17 Feb 2025 23:20:13 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6Im5rSVVjZHlkbkl5OXN0YTlmWHJ3Wnc9PSIsInZhbHVlIjoiTDJ2d2hrbGlDemNicjFCTWxzMDA3R0ZqM0lsSVJKUGcrVXUzRzNQWGNMOXFFRWpGL2x3OUhrb210V1FJYTJaN1h2YmtOS0dlVGdJaEZiRWdVREx0SkFCQ3dLaFhkYkFUcGdxdXVCeXh4VFdMVjI5UlhuVmg5ckpIb0JueWZMQUwiLCJtYWMiOiJiN2RhYzc2OGRmOWZiOTQxNTY1MjEwM2Y2YWEyNzM2YThmNTk1MWQ0ZmU5MTc5ZWMwOWQwYTI0ZWMwNTkzZjFmIiwidGFnIjoiIn0%3D; expires=Thu, 20 Feb 2025 11:20:13 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6Im5rSVVjZHlkbkl5OXN0YTlmWHJ3Wnc9PSIsInZhbHVlIjoiTDJ2d2hrbGlDemNicjFCTWxzMDA3R0ZqM0lsSVJKUGcrVXUzRzNQWGNMOXFFRWpGL2x3OUhrb210V1FJYTJaN1h2YmtOS" 1 => "alphaeurekaselectnet_session=eyJpdiI6Im5kUTN6SGZPTXBiMlRaQzJ6R2VxcUE9PSIsInZhbHVlIjoiOXRZWTl3eFgvRWt3QjhYVU0zT2grSXB0TjlMOE92aVV5RVJGb2U3bnNGMFRCaHNKbkJEdnVtRk0zMGt1YW9aYWIxeEtKME5pMFJ0SEVQY3FmMjJzZ1lhSlI4K3FoQ3grMWtNTlREOXJvb0pDODlhOFVqNHlWeTFLQXVUc2EyNzciLCJtYWMiOiIxZDVhZjIzMjYyMTZhOGM3NWYyN2Y2NDI3ZGU3MTgwNzBhZTIyYmRhNjUxNDU1NjgyODgzNTI2OTVkNGQzZTJjIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6Im5kUTN6SGZPTXBiMlRaQzJ6R2VxcUE9PSIsInZhbHVlIjoiOXRZWTl3eFgvRWt3QjhYVU0zT2grSXB0TjlMOE92aVV5RVJGb2U3bnNGMFRCaHNKbkJEdnVtRk0" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6Im5rSVVjZHlkbkl5OXN0YTlmWHJ3Wnc9PSIsInZhbHVlIjoiTDJ2d2hrbGlDemNicjFCTWxzMDA3R0ZqM0lsSVJKUGcrVXUzRzNQWGNMOXFFRWpGL2x3OUhrb210V1FJYTJaN1h2YmtOS0dlVGdJaEZiRWdVREx0SkFCQ3dLaFhkYkFUcGdxdXVCeXh4VFdMVjI5UlhuVmg5ckpIb0JueWZMQUwiLCJtYWMiOiJiN2RhYzc2OGRmOWZiOTQxNTY1MjEwM2Y2YWEyNzM2YThmNTk1MWQ0ZmU5MTc5ZWMwOWQwYTI0ZWMwNTkzZjFmIiwidGFnIjoiIn0%3D; expires=Thu, 20-Feb-2025 11:20:13 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6Im5rSVVjZHlkbkl5OXN0YTlmWHJ3Wnc9PSIsInZhbHVlIjoiTDJ2d2hrbGlDemNicjFCTWxzMDA3R0ZqM0lsSVJKUGcrVXUzRzNQWGNMOXFFRWpGL2x3OUhrb210V1FJYTJaN1h2YmtOS" 1 => "alphaeurekaselectnet_session=eyJpdiI6Im5kUTN6SGZPTXBiMlRaQzJ6R2VxcUE9PSIsInZhbHVlIjoiOXRZWTl3eFgvRWt3QjhYVU0zT2grSXB0TjlMOE92aVV5RVJGb2U3bnNGMFRCaHNKbkJEdnVtRk0zMGt1YW9aYWIxeEtKME5pMFJ0SEVQY3FmMjJzZ1lhSlI4K3FoQ3grMWtNTlREOXJvb0pDODlhOFVqNHlWeTFLQXVUc2EyNzciLCJtYWMiOiIxZDVhZjIzMjYyMTZhOGM3NWYyN2Y2NDI3ZGU3MTgwNzBhZTIyYmRhNjUxNDU1NjgyODgzNTI2OTVkNGQzZTJjIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6Im5kUTN6SGZPTXBiMlRaQzJ6R2VxcUE9PSIsInZhbHVlIjoiOXRZWTl3eFgvRWt3QjhYVU0zT2grSXB0TjlMOE92aVV5RVJGb2U3bnNGMFRCaHNKbkJEdnVtRk0" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "Bs9X3CK9J8kh5UVcKY35yw5wQemLBepxapqwedXS" "uc_cart_id" => "cbfd2aa8bfd31ffbf9b56a1a18c48bbd" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/4710" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-17 23:20:13GET/chapter/4710112195