tetano
Editor, Senior Moderator
Virus Res
. 2024 Mar 16:343:199356.
doi: 10.1016/j.virusres.2024.199356. Online ahead of print. Drug repurposing screen to identify inhibitors of the RNA polymerase (nsp12) and helicase (nsp13) from SARS-CoV-2 replication and transcription complex
Maria Kuzikov[SUP] 1 [/SUP], Jeanette Reinshagen[SUP] 2 [/SUP], Krzysztof Wycisk[SUP] 3 [/SUP], Angela Corona[SUP] 4 [/SUP], Francesca Esposito[SUP] 4 [/SUP], Paolo Malune[SUP] 4 [/SUP], Candida Manelfi[SUP] 5 [/SUP], Daniela Iaconis[SUP] 5 [/SUP], Andrea Beccari[SUP] 5 [/SUP], Enzo Tramontano[SUP] 4 [/SUP], Marcin Nowotny[SUP] 3 [/SUP], Björn Windshügel[SUP] 6 [/SUP], Philip Gribbon[SUP] 2 [/SUP], Andrea Zaliani[SUP] 2 [/SUP]
Affiliations
Coronaviruses contain one of the largest genomes among the RNA viruses, coding for 14-16 non-structural proteins (nsp) that are involved in proteolytic processing, genome replication and transcription, and four structural proteins that build the core of the mature virion. Due to conservation across coronaviruses, nsps form a group of promising drug targets as their inhibition directly affects viral replication and, therefore, progression of infection. A minimal but fully functional replication and transcription complex was shown to be formed by one RNA-dependent RNA polymerase (nsp12), one nsp7, two nsp8 accessory subunits, and two helicase (nsp13) enzymes. Our approach involved, targeting nsp12 and nsp13 to allow multiple starting point to interfere with virus infection progression. Here we report a combined in-vitro repurposing screening approach, identifying new and confirming reported SARS-CoV-2 nsp12 and nsp13 inhibitors.
Keywords: Drug repurposing; Helicase; RNA-dependent RNA polymerase; SARS-CoV-2; Screening.
. 2024 Mar 16:343:199356.
doi: 10.1016/j.virusres.2024.199356. Online ahead of print. Drug repurposing screen to identify inhibitors of the RNA polymerase (nsp12) and helicase (nsp13) from SARS-CoV-2 replication and transcription complex
Maria Kuzikov[SUP] 1 [/SUP], Jeanette Reinshagen[SUP] 2 [/SUP], Krzysztof Wycisk[SUP] 3 [/SUP], Angela Corona[SUP] 4 [/SUP], Francesca Esposito[SUP] 4 [/SUP], Paolo Malune[SUP] 4 [/SUP], Candida Manelfi[SUP] 5 [/SUP], Daniela Iaconis[SUP] 5 [/SUP], Andrea Beccari[SUP] 5 [/SUP], Enzo Tramontano[SUP] 4 [/SUP], Marcin Nowotny[SUP] 3 [/SUP], Björn Windshügel[SUP] 6 [/SUP], Philip Gribbon[SUP] 2 [/SUP], Andrea Zaliani[SUP] 2 [/SUP]
Affiliations
- PMID: 38490582
- DOI: 10.1016/j.virusres.2024.199356
Coronaviruses contain one of the largest genomes among the RNA viruses, coding for 14-16 non-structural proteins (nsp) that are involved in proteolytic processing, genome replication and transcription, and four structural proteins that build the core of the mature virion. Due to conservation across coronaviruses, nsps form a group of promising drug targets as their inhibition directly affects viral replication and, therefore, progression of infection. A minimal but fully functional replication and transcription complex was shown to be formed by one RNA-dependent RNA polymerase (nsp12), one nsp7, two nsp8 accessory subunits, and two helicase (nsp13) enzymes. Our approach involved, targeting nsp12 and nsp13 to allow multiple starting point to interfere with virus infection progression. Here we report a combined in-vitro repurposing screening approach, identifying new and confirming reported SARS-CoV-2 nsp12 and nsp13 inhibitors.
Keywords: Drug repurposing; Helicase; RNA-dependent RNA polymerase; SARS-CoV-2; Screening.