Drug repurposing screen to identify inhibitors of the RNA polymerase (nsp12) and helicase (nsp13) from SARS-CoV-2 replication and transcription complex

被引：8

作者：

Kuzikov, Maria ^{[1
,2
,3
,4
]}

Reinshagen, Jeanette ^{[1
,2
,3
]}

Wycisk, Krzysztof ^{[5
]}

Corona, Angela ^{[6
]}

Esposito, Francesca ^{[6
]}

Malune, Paolo ^{[6
]}

Manelfi, Candida ^{[7
]}

Iaconis, Daniela ^{[7
]}

Beccari, Andrea ^{[7
]}

Tramontano, Enzo ^{[6
]}

Nowotny, Marcin ^{[5
]}

Windshuegel, Bjorn ^{[4
]}

Gribbon, Philip ^{[1
,2
,3
]}

Zaliani, Andrea ^{[1
,2
,3
]}

机构：

[1] Fraunhofer Inst Translat Med & Pharmacol ITMP, Schnackenburgallee 114, D-22525 Hamburg, Germany

[2] Fraunhofer Cluster Excellence Immune Mediated Dis, Schnackenburgallee 114, D-22525 Hamburg, Germany

[3] Theodor Stern Kai 7, D-60590 Frankfurt, Germany

[4] Constructor Univ, Sch Sci, Campus Ring 1, D-28759 Bremen, Germany

[5] Int Inst Mol & Cell Biol, Lab Prot Struct, 4 Ks Trojdena St, PL-02109 Warsaw, Poland

[6] Cittadella Univ Monserrato, Dipartimento Sci & Ambiente, SS 554, Cagliari, Monserrato, Italy

[7] Dompe Farmaceut SpA, EXSCALATE, Via Tommaso De Amics,95, I-80131 Naples, Italy

来源：

VIRUS RESEARCH | 2024年 / 343卷

基金：

欧盟地平线“2020”;

关键词：

SARS-CoV-2; Helicase; RNA-dependent RNA polymerase; Screening; Drug repurposing; ACUTE RESPIRATORY SYNDROME; SARS-CORONAVIRUS NSP12; HEPATITIS; COMPOUND;

D O I：

10.1016/j.virusres.2024.199356

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页数：11

共 55 条

[41] Biochemical analysis of SARS-CoV-2 Nsp13 helicase implicated in COVID-19 and factors that regulate its catalytic functions [J].