Last update 01 Nov 2024

DNA-directed RNA polymerase

Last update 01 Nov 2024

Basic Info

Synonyms-

Introduction-

Drugs associated with DNA-directed RNA polymerase

DUP-105

Target

DNA-directed RNA polymerase

Mechanism

DNA RNA polymerase inhibitors

Active Org.-

Originator Org.

Bristol Myers Squibb Co.

Active Indication-

Inactive Indication

Anaerobic bacterial infection [+1]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

RBL-1

Target

DNA-directed RNA polymerase

Mechanism

DNA RNA polymerase inhibitors

Active Org.-

Originator Org.

Cytogenix, Inc.

Active Indication-

Inactive Indication

Bacterial Infections

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

EPB-500

Target

DNA-directed RNA polymerase

Mechanism

DNA RNA polymerase inhibitors

Active Org.-

Originator Org.

Epiphany Biosciences, Inc.

Active Indication-

Inactive Indication

Hepatitis C

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with DNA-directed RNA polymerase

100 Translational Medicine associated with DNA-directed RNA polymerase

0 Patents (Medical) associated with DNA-directed RNA polymerase

Literatures (Medical) associated with DNA-directed RNA polymerase

12 Jul 2023·Animals : an open access journal from MDPI

In Silico Analysis of Honey Bee Peptides as Potential Inhibitors of Capripoxvirus DNA-Directed RNA Polymerase.

Article

Author: Mahrosh, Hafiza Salaha ; Mustafa, Ghulam ; Ahmed, Sibtain ; Arif, Rawaba ; Ebaid, Hossam ; Salman, Mahwish ; Ali, Muhammad

The genus Capripoxvirus belongs to the Poxviridae family. The sheeppox, goatpox, and lumpy skin disease viruses are three species of this genus with 96% identity in their genomes. These are financially devastating viral infections among cattle, which cause a reduction in animal products and lead to a loss in livestock industries. In the current study, the phylogenetic analysis was carried out to reveal the evolutionary relationships of Capripoxvirus species (i.e., sheeppox virus (SPPV), goatpox virus (GTPV), and lumpy skin disease virus (LSDV)) with other viruses from the Poxviridae family with >96% query coverage to find the similarity index among all members. The three viruses (i.e., SPPV, GTPV, and LSDV) joined the clade of Capripoxvirus of the Poxviridae family in the phylogenetic tree and exhibited close evolutionary relationships. The multiple sequence alignment using ClustalOmega revealed significant variations in the protein sequences of the DNA-dependent RNA polymerase of SPPV, GTPV, and LSDV. The three-dimensional structures of five selected bee peptides and DNA-directed RNA polymerase of SPPV, GTPV, and LSDV were predicted using trRosetta and I-TASSER and used for molecular docking and simulation studies. The protein-protein docking was carried out using HADDOCK server to explore the antiviral activity of peptides as honey bee proteins against SPPV, GTPV, and LSDV. In total, five peptides were docked to DNA-directed RNA polymerase of these viruses. The peptides mellitin and secapin-1 displayed the lowest binding scores (-106.9 +/- 7.2 kcal/mol and -101.4 +/- 11.3 kcal/mol, respectively) and the best patterns with stable complexes. The molecular dynamics simulation indicated that the complex of protein DNA-dependent RNA polymerase and the peptide melittin stayed firmly connected and the peptide binding to the receptor protein was stable. The findings of this study provide the evidence of bee peptides as potent antimicrobial agents against sheeppox, goatpox, and lumpy skin disease viruses with no complexity.

01 May 2023·Journal of cellular biochemistry

Drug repurposing for Mpox: Discovery of small molecules as potential inhibitors against DNA-dependent RNA polymerase using molecular modeling approach.

Article

Author: Dutt, Mansi ; Ndishimye, Pacifique ; Kelvin, Alyson A ; Kelvin, David J ; Rout, Madhusmita ; Martinez, Gustavo ; Kumar, Anuj ; Dehury, Budheswar

Mpox (formerly Monkeypox), a zoonotic illness caused by the Mpox virus, belongs to the Orthopoxvirus genus in the family Poxviridae. To design and develop effective antiviral therapeutics against DNA viruses, the DNA-dependent RNA polymerase (DdRp) of poxviruses has emerged as a promising drug target. In the present study, we modeled the three-dimensional (3D) structure of DdRp using a template-based homology approach. After modeling, virtual screening was performed to probe the molecular interactions between 1755 Food and Drug Administration-approved small molecule drugs (≤500 molecular weight) and the DdRp of Mpox. Based on the binding affinity and molecular interaction patterns, five drugs, lumacaftor (-11.7 kcal/mol), conivaptan (-11.7 kcal/mol), betulinic acid (-11.6 kcal/mol), fluspirilene (-11.3 kcal/mol), and imatinib (-11.2 kcal/mol), have been ranked as the top drug compounds interacting with Mpox DdRp. Complexes of these shortlisted drugs with DdRp were further evaluated using state-of-the-art all-atoms molecular dynamics (MD) simulations on 200 nanoseconds followed by principal component analysis (PCA). MD simulations and PCA results revealed highly stable interactions of these small drugs with DdRp. After due validation in wet-lab using available in vitro and in vivo experiments, these repurposed drugs can be further utilized for the treatment of contagious Mpox virus. The outcome of this study may establish a solid foundation to screen repurposed and natural compounds as potential antiviral therapeutics against different highly pathogenic viruses.

01 May 2022·GeneQ3 · BIOLOGY

Study on population structure of kiwifruit and GWAS for hairiness character

Q3 · BIOLOGY

Article

Author: Yu, Yuehua ; Qu, Dong ; Zhang, Yu ; Zheng, Shimao ; Wang, Yuexing ; Sun, Wang

BACKGROUNDA total of 74,936 SNPs were employed to carry out population structure and genome-wide association studies and post-GWAS for hairiness character of the fifty-six samples including thirty-six Actinidia chinensis var. deliciosa, eighteen A. chinensis var. chinensis, and two A. polygama in the light of morphological observations.RESULTSThe percentage of heterozygous sites of A. chinensis var. deliciosa is higher than that of A. chinensis var. chinensis, which could be one of the reasons for A. chinensis var. deliciosa high disease resistance. Fifty-six samples were divided into two subgroups, in which the genetic distance, ranged from 0.17 to 0.99, according to their genetic divergence. Analysis of molecular variance shows that the frequency of genetic variations within the population is 83.53% and 16.47% between populations. F_st between the two populations is 0.14, and N_m is 1.60. Set at α ≤ 0.05, a total of 327 SNPs and 260 haplotypes were related to the hairiness character. A total of 246 proteins were annotated using GO and KEGG analyses, which indicated the membrane-related genes and stress-resistant metabolic pathways are related to the hairiness character of leaves, stems, and peels of kiwifruit. Protein interaction analysis showed that DNA-directed RNA polymerase was an important node protein that interacted with many proteins.CONCLUSIONSThe genetic basic in the fifty-six genotypes was rich. The results of clustering and morphological observations are not completely consistent, indicating the hairiness character play an important role in the classification of kiwifruit, in which two A. polygama were clustered together with those of A. chinensis var. chinensis. Phylogeny and haplotype analysis showed that the evolution of A. chinensis var. chinensis is later than that of A. chinensis var. deliciosa in A. chinesis. The loss of hairiness character on leaves, stems and peels of A. chinensis var. chinensis compare with A. chinensis var. deliciosa, which is also the result of its poor resistance.

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DNA-directed RNA polymerase

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