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. 2022 Feb;40(3):1101-1108.
doi: 10.1080/07391102.2020.1822209. Epub 2020 Sep 18.

A computational approach to drug repurposing against SARS-CoV-2 RNA dependent RNA polymerase (RdRp)

Giovanni Ribaudo  1 , Alberto Ongaro  1 , Erika Oselladore  2 , Giuseppe Zagotto  2 , Maurizio Memo  1 , Alessandra Gianoncelli  1
Affiliations

A computational approach to drug repurposing against SARS-CoV-2 RNA dependent RNA polymerase (RdRp)

Giovanni Ribaudo et al. J Biomol Struct Dyn. 2022 Feb.

Abstract

The spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a worldwide outbreak of coronavirus disease 19 (COVID-19), which rapidly evolved as a global concern. The efforts of the scientific community are pointed towards the identification of promptly available therapeutic options. RNA-dependent RNA polymerase (RdRp) is a promising target for developing small molecules to contrast SARS-CoV-2 replication. Modern computational tools can boost identification and repurposing of known drugs targeting RdRp. We here report the results regarding the screening of a database containing more than 8800 molecules, including approved, experimental, nutraceutical, illicit, withdrawn and investigational compounds. The molecules were docked against the cryo-electron microscopy structure of SARS-CoV-2 RdRp, optimized by means of molecular dynamics (MD) simulations. The adopted three-stage ensemble docking study underline that compounds formerly developed as kinase inhibitors may interact with RdRp.Communicated by Ramaswamy H. Sarma.

Keywords: RdRp; SARS-CoV-2; molecular modelling; remdesivir; repurposing.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Gaussian plot representing the distribution of the docking values obtained with the MM-GBSA protocol applied to the poses resulting from the XP docking stage.
Figure 2.
Figure 2.
Best scoring compounds according to MM-GBSA screening.
Figure 3.
Figure 3.
Docked pose of the ligands bedoradrine (a, b) and palbociclib (c, d) in RdRp showing the main interactions of the complex and two-dimensional interaction maps.
See this image and copyright information in PMC

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References

    1. Abedi, F., Rezaee, R., & Karimi, G. (2020). Plausibility of therapeutic effects of Rho kinase inhibitors against severe acute respiratory syndrome Coronavirus 2 (COVID-19). Pharmacological Research, 156, 104808. 10.1016/j.phrs.2020.104808 - DOI - PMC - PubMed
    1. Beigel, J. H., Tomashek, K. M., Dodd, L. E., Mehta, A. K., Zingman, B. S., Kalil, A. C., Hohmann, E., Chu, H. Y., Luetkemeyer, A., Kline, S., Lopez de Castilla, D., Finberg, R. W., Dierberg, K., Tapson V., Hsieh, L., Patterson, T. F., Paredes, R., Sweeney, D. A., Short, W. R., … Lane, H. C. (2020). Remdesivir for the treatment of Covid-19—Preliminary Report. New England Journal of Medicine. 10.1056/NEJMoa2007764 - DOI - PubMed
    1. Bettiol, A., Marconi, E., Lombardi, N., Crescioli, G., Gherlinzoni, F., Walley, T., Vannacci, A., Chinellato, A., & Giusti, P. (2018). Pattern of use and long-term safety of tyrosine kinase inhibitors: A decade of real-world management of chronic myeloid leukemia. Clinical Drug Investigation, 38(9), 837–844. 10.1007/s40261-018-0676-7 - DOI - PubMed
    1. Bhardwaj, V. K., Singh, R., Sharma, J., Das, P., & Purohit, R. (2020). Structural based study to identify new potential inhibitors for dual specificity tyrosine-phosphorylation- regulated kinase. Computer Methods and Programs in Biomedicine, 194, 105494. 10.1016/j.cmpb.2020.105494 - DOI - PubMed
    1. Bhardwaj, V. K., Singh, R., Sharma, J., Rajendran, V., Purohit, R., & Kumar, S. (2020). Identification of bioactive molecules from tea plant as SARS-CoV-2 main protease inhibitors. Journal of Biomolecular Structure and Dynamics, 1–10. 10.1080/07391102.2020.1766572 - DOI - PMC - PubMed

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