Exploring new antiviral targets for influenza and COVID-19: Mapping promising hot spots in viral RNA polymerases.

Autor: Figueiredo-Nunes I; Host-Pathogen Interaction Unit, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003, Lisbon, Portugal., Trigueiro-Louro J; Host-Pathogen Interaction Unit, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003, Lisbon, Portugal; Antiviral Resistance Lab, Research & Development Unit, Infectious Diseases Department, Instituto Nacional de Saúde Doutor Ricardo Jorge, IP, Av. Padre Cruz, 1649-016, Lisbon, Portugal. Electronic address: joao.louro@insa.min-saude.pt., Rebelo-de-Andrade H; Host-Pathogen Interaction Unit, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003, Lisbon, Portugal; Antiviral Resistance Lab, Research & Development Unit, Infectious Diseases Department, Instituto Nacional de Saúde Doutor Ricardo Jorge, IP, Av. Padre Cruz, 1649-016, Lisbon, Portugal. Electronic address: h.rebelo.andrade@insa.min-saude.pt.
Jazyk: angličtina
Zdroj: Virology [Virology] 2023 Jan; Vol. 578, pp. 45-60. Date of Electronic Publication: 2022 Nov 18.
DOI: 10.1016/j.virol.2022.11.001
Abstrakt: Influenza and COVID-19 are infectious respiratory diseases that represent a major concern to public health with social and economic impact worldwide, for which the available therapeutic options are not satisfactory. The RdRp has a central role in viral replication and thus represents a major target for the development of antiviral approaches. In this study, we focused on Influenza A virus PB1 polymerase protein and the betacoronaviruses nsp12 polymerase protein, considering their functional and structural similarities. We have performed conservation and druggability analysis to map conserved druggable regions, that may have functional or structural importance in these proteins. We disclosed the most promising and new targeting regions for the discovery of new potential polymerase inhibitors. Conserved druggable regions of putative interaction with favipiravir and molnupiravir were also mapped. We have also compared and integrated the current findings with previous research.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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