Frontiers in Clinical Drug Research-Anti Infectives

Volume: 4

Recent Advances in the Development of Antiviral Approaches against Hemorrhagic-Fever-Causing Arenaviruses

Author(s): Viviana Castilla, Jesus E. Brunetti, Maria N. Armiento and Luis A. Scolaro

Pp: 58-92 (35)

DOI: 10.2174/9781681084879117040005

* (Excluding Mailing and Handling)

Abstract

Arenaviruses, enveloped viruses containing a bisegmented single-stranded RNA genome with ambisense coding strategy, include important hemorrhagic-fevercausing viruses representing a public health threat in endemic areas of Africa and South America. In spite of the danger of pathogenic arenaviruses and their increased emergence in recent years, no specific and safe chemotherapy for these viruses is currently available. This chapter covers recent advances in the development of antiviral strategies to face arenavirus infections. New insights in molecular aspects of virus replication and virus-host interactions have allowed the identification of viral and cellular factors as potential target for antiviral therapy. We will revise the main features of arenavirus biology and the mechanism of antiviral action of different molecules derived from natural sources, chemical synthesis and rational structure-based antiviral drug design. The advantage of targeting viral and cell host factors as complementary approaches for therapy intervention will be discussed. We will particularly discuss the use of novel inhibitory strategies and the main advances in the development of innovative screening platforms.


Keywords: Attachment, Antiviral activity, Arenavirus, Argentine hemorrhagic fever, Budding, Candid #1, Emerging viruses, Entry, Favipiravir, Guanarito virus, Hemorrhagic fevers, High-throughput screening, Interferon, Junin virus, Lassa fever, Lassa virus, Lujo virus, Machupo virus, Membrane fusion, Monoclonal antibody, Pathogenesis, Peptide, Replication, Reverse genetic, Ribavirin, Sabia virus, Small interfering RNA, Small molecule, Therapy, Uncoating.

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      • 15. middleware::check_user_access:114
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      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
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      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
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      • 14. app/Models/Subject.php:238
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      • 16. app/Models/Subject.php:255
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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
      • 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 <= 316674267 and j.to_ip >=316674267 )) and ((j.from_date <= 1740456993 and j.to_date >= 1740456993 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 11118) 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 <= 316674267 and j.to_ip >=316674267 )) and ((j.from_date <= 1740456993 and j.to_date >= 1740456993 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 11118) 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 <= 316674267 and j.to_ip >=316674267 )) and ((j.from_date <= 1740456993 and j.to_date >= 1740456993 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 11118)
      920μsalphaeurekaselec_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` = 2275 and `b`.`banner_from_date` <= 1740456993 and `b`.`banner_to_date` >= 1740456993 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.52msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 2275
      • 3: 1740456993
      • 4: 1740456993
      • 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='0dd15f82cc7c9558bae690c9ec65f391'
      280μsalphaeurekaselec_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
    30Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        yUzTUmYME2MHCPehcWUQ7BncJ32fB410W7dG1jZE
        uc_cart_id
        0dd15f82cc7c9558bae690c9ec65f391
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/chapter/11118" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/11118
        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:8 [ "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "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" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        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 => "Tue, 25 Feb 2025 04:16:33 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IitWenBJWDh3RGhhMWdMOG03NGpSYmc9PSIsInZhbHVlIjoid0hwTzhmS0xSSzNKOGpZQnljL2ZuY1FkTmxrOWo3OUE2MXFLY01ZYlZCSVVUbk9ldWtGN3JFQ2xYYlNNeXlvMVVxekREakdkSGkrRDYweDZZRXQ2YW9pbzMxWm16RDMvUWp2U0Y2ak0xem91L1l3ZkpEWlJobzZiOW1CeUpxV04iLCJtYWMiOiJlZWM3ZTI3MWJmYmM1NzczMzQzMDlkZmM1N2EzODM3NTQ1ZmJkYWRlZGY4ZTY3ZGJlZmMxY2UyODBkNjNkOTk5IiwidGFnIjoiIn0%3D; expires=Thu, 27 Feb 2025 16:16:33 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IitWenBJWDh3RGhhMWdMOG03NGpSYmc9PSIsInZhbHVlIjoid0hwTzhmS0xSSzNKOGpZQnljL2ZuY1FkTmxrOWo3OUE2MXFLY01ZYlZCSVVUbk9ldWtGN3JFQ2xYYlNNeXlvMVVxekREa" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImtaalY3dVdWK0lEZldnYU9IM3VMMmc9PSIsInZhbHVlIjoiOHg2SHdZUGFQcGQ2ZlU3NzMrUHc4eXBLejV2MVBlMVVhUW5NaENSUE9jaTNkTGt5aVZ6Q09MUUdOcE9GODFSS1gyM0RYNkprMG9CNFVzbHY1NHFQUjl2Snp2UzB1UDFzdkwyS1dsZnVkQnc4bjJWQlVadlhjcDYxeGJmS2MxUksiLCJtYWMiOiJiMTUzNjJiNzRhYjAyZTJhMTc3MGVkODgwNzlmN2FhMTljZTlmMDY3NzEzNjE2YTIzOGFlYjRiODU0MTg2ZTZhIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6ImtaalY3dVdWK0lEZldnYU9IM3VMMmc9PSIsInZhbHVlIjoiOHg2SHdZUGFQcGQ2ZlU3NzMrUHc4eXBLejV2MVBlMVVhUW5NaENSUE9jaTNkTGt5aVZ6Q09MUUd" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IitWenBJWDh3RGhhMWdMOG03NGpSYmc9PSIsInZhbHVlIjoid0hwTzhmS0xSSzNKOGpZQnljL2ZuY1FkTmxrOWo3OUE2MXFLY01ZYlZCSVVUbk9ldWtGN3JFQ2xYYlNNeXlvMVVxekREakdkSGkrRDYweDZZRXQ2YW9pbzMxWm16RDMvUWp2U0Y2ak0xem91L1l3ZkpEWlJobzZiOW1CeUpxV04iLCJtYWMiOiJlZWM3ZTI3MWJmYmM1NzczMzQzMDlkZmM1N2EzODM3NTQ1ZmJkYWRlZGY4ZTY3ZGJlZmMxY2UyODBkNjNkOTk5IiwidGFnIjoiIn0%3D; expires=Thu, 27-Feb-2025 16:16:33 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IitWenBJWDh3RGhhMWdMOG03NGpSYmc9PSIsInZhbHVlIjoid0hwTzhmS0xSSzNKOGpZQnljL2ZuY1FkTmxrOWo3OUE2MXFLY01ZYlZCSVVUbk9ldWtGN3JFQ2xYYlNNeXlvMVVxekREa" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImtaalY3dVdWK0lEZldnYU9IM3VMMmc9PSIsInZhbHVlIjoiOHg2SHdZUGFQcGQ2ZlU3NzMrUHc4eXBLejV2MVBlMVVhUW5NaENSUE9jaTNkTGt5aVZ6Q09MUUdOcE9GODFSS1gyM0RYNkprMG9CNFVzbHY1NHFQUjl2Snp2UzB1UDFzdkwyS1dsZnVkQnc4bjJWQlVadlhjcDYxeGJmS2MxUksiLCJtYWMiOiJiMTUzNjJiNzRhYjAyZTJhMTc3MGVkODgwNzlmN2FhMTljZTlmMDY3NzEzNjE2YTIzOGFlYjRiODU0MTg2ZTZhIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6ImtaalY3dVdWK0lEZldnYU9IM3VMMmc9PSIsInZhbHVlIjoiOHg2SHdZUGFQcGQ2ZlU3NzMrUHc4eXBLejV2MVBlMVVhUW5NaENSUE9jaTNkTGt5aVZ6Q09MUUd" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "yUzTUmYME2MHCPehcWUQ7BncJ32fB410W7dG1jZE" "uc_cart_id" => "0dd15f82cc7c9558bae690c9ec65f391" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/chapter/11118" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 04:16:33GET/chapter/111181121932