Frontiers in Anti-Infective Drug Discovery

Volume: 6

Recent Advances in Molecular Scaffolds towards the Identification of Novel Receptors in the Treatment of Hepatitis Diseases

Author(s): Naseem Ahmed

Pp: 335-481 (147)

DOI: 10.2174/9781681084794117060007

* (Excluding Mailing and Handling)

Abstract

Widespread outbreak of numerous infectious diseases across the globe has created awareness in chemists for the novel design and synthesis of lead molecules. Like hepatitis is one of the viral infectious disease, damages the liver function and therefore causes major complications, even leads to death in many cases. More than one third population of the world is affected by hepatitis. Different viral hepatitis are Hepatitis A (HAV), B(HBV), C(HCV), D(HDV) and E(HEV), depending upon the infecting virus type. Hepatitis A and E viruses are usually contacted after eating and drinking contaminated food and water. While, HBV, HCV and HDV are transmitted through contaminated blood. Hepatitis B and C are typically chronic, but HDV may be acute or chronic in nature. Non-viral hepatitis are also reported either due to alcohol consumption or metabolic disorder medications, which causes the liver stress or inflammation. The treatment options of hepatitis vary depending upon what form you have and what caused the infection. Until recently, the treatment of hepatitis B has been reported with interferons alone or pegylated interferons while hepatitis C with interferons only or pegylated interferon (PEG-IFN) and ribavirin in combination, both are less successful (35-40%) and have side effects. Thus, a virus-specific, efficient and drug resistant free, anti-HBV and anti-HCV therapeutics are needed. Since 2011, the use of new drugs in targeting NS3/4A protease, NS5B polymerase and NS5A enzymes have enhanced treatment rates (70-90%) but still showed some side effects. Furthermore, inhibitors are at diverse stages of clinical development for NS5B and NS5A polymerase targets. Future design and synthesis of novel drugs must address genetic difference in HBV and HCV with least drug resistance. Also, for the genetic over-expression in HCV, a number of investigational techniques have developed which led to the comprehensive analysis of different aspects of viral life-cycle and interactions between virus and host (human). Thus, a rising list of targets for therapeutic involvement has been revealed. The directly acting anti-virals (DAAs) is another therapy method which helps in exploring novel and highly developed combinations of drugs. In this chapter, we discuss the synthetic advances of receptor based anti-viral scaffolds in hepatitis, which afforded significant numbers of agents such as drugs or drug leads, their mechanisms of action (MOAs), structure-activity relationships (SARs) and future structural perspectives as drug candidates.


Keywords: Antiviral agents, Combination therapy, Direct acting anti-virals (DAAs), Drug resistance, Hepatitis, Receptor inhibitors, Structure-activity relationships (SARs).

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      • 11. app/Models/ContentAccess.php:647
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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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      • 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 <= 316567616 and j.to_ip >=316567616 )) and ((j.from_date <= 1740460246 and j.to_date >= 1740460246 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 10848) 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 <= 316567616 and j.to_ip >=316567616 )) and ((j.from_date <= 1740460246 and j.to_date >= 1740460246 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 10848) 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 <= 316567616 and j.to_ip >=316567616 )) and ((j.from_date <= 1740460246 and j.to_date >= 1740460246 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 10848)
      580μsalphaeurekaselec_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` = 2254 and `b`.`banner_from_date` <= 1740460246 and `b`.`banner_to_date` >= 1740460246 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.02msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 2254
      • 3: 1740460246
      • 4: 1740460246
      • 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='f5a50918204bf71c7f4598599ee56b34'
      190μsalphaeurekaselec_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
    7Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        M83jJlOf663DoTQEcl45ByiCRYynwvtO9Ag2K5aQ
        uc_cart_id
        f5a50918204bf71c7f4598599ee56b34
        _previous
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        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
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        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
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        request_cookies
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        response_headers
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 05:10:46GET/chapter/10848112199