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Dual computational and biological assessment of some promising nucleoside analogs against the COVID-19-Omicron variant

Abdalla, Mohnad ; Rabie, Amgad M.

Computational biology and chemistry, 2023-06, Vol.104, p.107768-107768, Article 107768 [Periódico revisado por pares]

England: Elsevier Ltd

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  • Título:
    Dual computational and biological assessment of some promising nucleoside analogs against the COVID-19-Omicron variant
  • Autor: Abdalla, Mohnad ; Rabie, Amgad M.
  • Assuntos: Anti-COVID-19 medication ; Anti-Omicron-BA.5 agent ; Coronaviral-2 RNA-dependent RNA polymerase (RdRp) ; Nucleic acid ligand ; Nucleos(t)ide analog ; Polymerase inhibitor ; Riboprine/Forodesine ; SARS-CoV-2 proofreading 3′-to-5′ exoribonuclease (ExoN)
  • É parte de: Computational biology and chemistry, 2023-06, Vol.104, p.107768-107768, Article 107768
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    ORCID iD: 0000-0002-1682-5547
    ORCID iD: 0000-0003-3681-114X
  • Descrição: Nucleoside analogs/derivatives (NAs/NDs) with potent antiviral activities are now deemed very convenient choices for the treatment of coronavirus disease 2019 (COVID-19) arisen by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. At the same time, the appearance of a new strain of SARS-CoV-2, the Omicron variant, necessitates multiplied efforts in fighting COVID-19. Counteracting the crucial SARS-CoV-2 enzymes RNA-dependent RNA polymerase (RdRp) and 3′-to-5′ exoribonuclease (ExoN) jointly altogether using the same inhibitor is a quite successful new plan to demultiplicate SARS-CoV-2 particles and eliminate COVID-19 whatever the SARS-CoV-2 subtype is (due to the significant conservation nature of RdRps and ExoNs in the different SARS-CoV-2 strains). Successive in silico screening of known NAs finally disclosed six different promising NAs, which are riboprine/forodesine/tecadenoson/nelarabine/vidarabine/maribavir, respectively, that predictably can act through the planned dual-action mode. Further in vitro evaluations affirmed the anti-SARS-CoV-2/anti-COVID-19 potentials of these NAs, with riboprine and forodesine being at the top. The two NAs are able to effectively antagonize the replication of the new virulent SARS-CoV-2 strains with considerably minute in vitro anti-RdRp and anti-SARS-CoV-2 EC50 values of 189 and 408 nM for riboprine and 207 and 657 nM for forodesine, respectively, surpassing both remdesivir and the new anti-COVID-19 drug molnupiravir. Furthermore, the favorable structural characteristics of the two molecules qualify them for varied types of isosteric and analogistic chemical derivatization. In one word, the present important outcomes of this comprehensive dual study revealed the anticipating repurposing potentials of some known nucleosides, led by the two NAs riboprine and forodesine, to successfully discontinue the coronaviral-2 polymerase/exoribonuclease interactions with RNA nucleotides in the SARS-CoV-2 Omicron variant (BA.5 sublineage) and accordingly alleviate COVID-19 infections, motivating us to initiate the two drugs' diverse anti-COVID-19 pharmacological evaluations to add both of them betimes in the COVID-19 therapeutic protocols. [Display omitted] •Mixed SARS-CoV-2 polymerase (RdRp) and exoribonuclease (ExoN) inhibition via nucleoside analogism is a very effective novel tactic for COVID-19 infection therapy.•Nucleoside analogs (NAs) are currently considered first choices in COVID-19 therapy.•Extensive computational investigations revealed 6 NAs with ideal anti-RdRp/ExoN features.•Riboprine and forodesine were ranked the top among the 6 NAs, with biochemical anti-RdRp EC50 values of 189 and 207 nM, respectively.•Riboprine and forodesine accordingly displayed excellent anti-SARS-CoV-2 EC50 values of 408 and 657 nM, respectively, against the Omicron variant.
  • Editor: England: Elsevier Ltd
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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