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Analysis of institutional authors

Sáez-álvarez YAuthorDel Aguila C.AuthorAgudo RCorresponding Author

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April 23, 2019
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Development of a fluorescence-based method for the rapid determination of Zika virus polymerase activity and the screening of antiviral drugs

Publicated to: Scientific Reports. 9 (5397): 5397- - 2019-12-01 9(5397), DOI: 10.1038/s41598-019-41998-1

Authors: Saez-Alvarez, Yanira; Arias, Armando; del Aguila, Carmen; Agudo, Ruben

Affiliations

Tech Univ Denmark, Life Sci & Bioengn Bldg, DK-2800 Lyngby, Denmark - Author
Univ San Pablo CEU, CEU Univ, Fac Farm, Madrid 28668, Spain - Author

Abstract

Zika virus (ZIKV) is an emerging pathogen that has been associated with large numbers of cases of severe neurologic disease, including Guillain-Barre syndrome and microcephaly. Despite its recent establishment as a serious global public health concern there are no licensed therapeutics to control this virus. Accordingly, there is an urgent need to develop methods for the high-throughput screening of antiviral agents. We describe here a fluorescence-based method to monitor the real-time polymerization activity of Zika virus RNA-dependent RNA polymerase (RdRp). By using homopolymeric RNA template molecules, de novo RNA synthesis can be detected with a fluorescent dye, which permits the specific quantification and kinetics of double-strand RNA formation. ZIKV RdRp activity detected using this fluorescence-based assay positively correlated with traditional assays measuring the incorporation of radiolabeled nucleotides. We also validated this method as a suitable assay for the identification of ZIKV inhibitors targeting the viral polymerase using known broad-spectrum inhibitors. The assay was also successfully adapted to detect RNA polymerization activity by different RdRps, illustrated here using purified RdRps from hepatitis C virus and foot-and-mouth disease virus. The potential of fluorescence-based approaches for the enzymatic characterization of viral polymerases, as well as for high-throughput screening of antiviral drugs, are discussed.

Keywords

AnimalsAntiviral agentsBiologyCell-cultureChain-reactionDependent rna-polymeraseDrug discoveryError catastropheFluorescenceGuillain-barre syndromeHepatitis-c virusHigh-throughput screening assaysHumansIdentificationMicrocephalyNs5 proteinNucleoside inhibitorsRibavirinRna-dependent rna polymeraseVirus replicationZika virusZika virus infection

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Scientific Reports due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2019, it was in position 17/71, thus managing to position itself as a Q1 (Primer Cuartil), in the category Multidisciplinary Sciences.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.42. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 13, 2025)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 1.17 (source consulted: FECYT Mar 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-12-05, the following number of citations:

  • WoS: 35
  • Scopus: 39
  • Europe PMC: 35

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-12-05:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 115.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 114 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 11.
  • The number of mentions on the social network X (formerly Twitter): 3 (Altmetric).
  • The number of mentions in news outlets: 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Denmark.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Sáez Álvarez, Yanira) and Last Author (Agudo Torres, Ruben).

the author responsible for correspondence tasks has been Agudo Torres, Ruben.

Awards linked to the item

We would like to thank to laboratory of Professor Esteban Domingo (Centro de Biologia Molecular Severo Ochoa, Madrid) for providing plasmids pET-28a3Dpol, pET-28aD338A, Jc1FLAG2(p7-nsGluc2a) and Jc1FLAG2(p7-nsGluc2a)/GNN, and Professor Luis Blanco (Centro de Biologia Molecular Severo Ochoa, Madrid) for allowing the use of his laboratory to perform the polymerization experiments in the presence of radiolabeled nucleotides. This work was supported by grants RYC-2015-17280 and BIO2017-85124-R from Ministerio de Economia, Industria y Competitividad. Y S-A. is the recipient of an FPI-predoctoral fellowship from Universidad CEU San Pablo. AA is the recipient of a Research project-1 grant from Independent Research Fund Denmark (Technology and Production Sciences, DFF-FTP), application number 6111-00104B.