Antiviral drug discovery: preparing for the next pandemic
- Adamson, Catherine S, Chibale, Kelly, Goss, Rebecca J M, Jaspars, Marcel, Newman, David J, Dorrington, Rosemary A
- Authors: Adamson, Catherine S , Chibale, Kelly , Goss, Rebecca J M , Jaspars, Marcel , Newman, David J , Dorrington, Rosemary A
- Date: 2021
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/177499 , vital:42827 , DOI: 10.1039/d0cs01118e
- Description: Clinically approved antiviral drugs are currently available for only 10 of the more than 220 viruses known to infect humans. The SARS-CoV-2 outbreak has exposed the critical need for compounds that can be rapidly mobilised for the treatment of re-emerging or emerging viral diseases, while vaccine development is underway. We review the current status of antiviral therapies focusing on RNA viruses, highlighting strategies for antiviral drug discovery and discuss the challenges, solutions and options to accelerate drug discovery efforts.
- Full Text:
- Date Issued: 2021
- Authors: Adamson, Catherine S , Chibale, Kelly , Goss, Rebecca J M , Jaspars, Marcel , Newman, David J , Dorrington, Rosemary A
- Date: 2021
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/177499 , vital:42827 , DOI: 10.1039/d0cs01118e
- Description: Clinically approved antiviral drugs are currently available for only 10 of the more than 220 viruses known to infect humans. The SARS-CoV-2 outbreak has exposed the critical need for compounds that can be rapidly mobilised for the treatment of re-emerging or emerging viral diseases, while vaccine development is underway. We review the current status of antiviral therapies focusing on RNA viruses, highlighting strategies for antiviral drug discovery and discuss the challenges, solutions and options to accelerate drug discovery efforts.
- Full Text:
- Date Issued: 2021
Unlocking the Diversity of Pyrroloiminoquinones Produced by Latrunculid Sponge Species
- Kalinski, Jarmo-Charles J, Krause, Rui W M, Parker-Nance, Shirley, Waterworth, Samantha C, Dorrington, Rosemary A
- Authors: Kalinski, Jarmo-Charles J , Krause, Rui W M , Parker-Nance, Shirley , Waterworth, Samantha C , Dorrington, Rosemary A
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/191802 , vital:45165 , xlink:href="https://doi.org/10.3390/md19020068"
- Description: Sponges of the Latrunculiidae family produce bioactive pyrroloiminoquinone alkaloids including makaluvamines, discorhabdins, and tsitsikammamines. The aim of this study was to use LC-ESI-MS/MS-driven molecular networking to characterize the pyrroloiminoquinone secondary metabolites produced by six latrunculid species. These are Tsitsikamma favus, Tsitsikamma pedunculata, Cyclacanthia bellae, and Latrunculia apicalis as well as the recently discovered species, Tsitsikamma nguni and Tsitsikamma michaeli. Organic extracts of 43 sponges were analyzed, revealing distinct species-specific chemical profiles. More than 200 known and unknown putative pyrroloiminoquinones and related compounds were detected, including unprecedented makaluvamine-discorhabdin adducts and hydroxylated discorhabdin I derivatives. The chemical profiles of the new species T. nguni closely resembled those of the known T. favus (chemotype I), but with a higher abundance of tsitsikammamines vs. discorhabdins. T. michaeli sponges displayed two distinct chemical profiles, either producing mostly the same discorhabdins as T. favus (chemotype I) or non- or monobrominated, hydroxylated discorhabdins. C. bellae and L. apicalis produced similar pyrroloiminoquinone chemistry to one another, characterized by sulfur-containing discorhabdins and related adducts and oligomers. This study highlights the variability of pyrroloiminoquinone production by latrunculid species, identifies novel isolation targets, and offers fundamental insights into the collision-induced dissociation of pyrroloiminoquinones.
- Full Text:
- Date Issued: 2021
- Authors: Kalinski, Jarmo-Charles J , Krause, Rui W M , Parker-Nance, Shirley , Waterworth, Samantha C , Dorrington, Rosemary A
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/191802 , vital:45165 , xlink:href="https://doi.org/10.3390/md19020068"
- Description: Sponges of the Latrunculiidae family produce bioactive pyrroloiminoquinone alkaloids including makaluvamines, discorhabdins, and tsitsikammamines. The aim of this study was to use LC-ESI-MS/MS-driven molecular networking to characterize the pyrroloiminoquinone secondary metabolites produced by six latrunculid species. These are Tsitsikamma favus, Tsitsikamma pedunculata, Cyclacanthia bellae, and Latrunculia apicalis as well as the recently discovered species, Tsitsikamma nguni and Tsitsikamma michaeli. Organic extracts of 43 sponges were analyzed, revealing distinct species-specific chemical profiles. More than 200 known and unknown putative pyrroloiminoquinones and related compounds were detected, including unprecedented makaluvamine-discorhabdin adducts and hydroxylated discorhabdin I derivatives. The chemical profiles of the new species T. nguni closely resembled those of the known T. favus (chemotype I), but with a higher abundance of tsitsikammamines vs. discorhabdins. T. michaeli sponges displayed two distinct chemical profiles, either producing mostly the same discorhabdins as T. favus (chemotype I) or non- or monobrominated, hydroxylated discorhabdins. C. bellae and L. apicalis produced similar pyrroloiminoquinone chemistry to one another, characterized by sulfur-containing discorhabdins and related adducts and oligomers. This study highlights the variability of pyrroloiminoquinone production by latrunculid species, identifies novel isolation targets, and offers fundamental insights into the collision-induced dissociation of pyrroloiminoquinones.
- Full Text:
- Date Issued: 2021
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