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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.
  • Abdalla M; Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Cultural West Road, Shandong Province 250012, PR China. Electronic address: mohnadabdalla200@gmail.com.
  • Rabie AM; Dr. Amgad Rabie's Research Lab. for Drug Discovery (DARLD), Mansoura City 35511, Mansoura, Dakahlia Governorate, Egypt; Head of Drug Discovery & Clinical Research Department, Dikernis General Hospital (DGH), Magliss El-Madina Street, Dikernis City 35744, Dikernis, Dakahlia Governorate, Egypt. Electronic address: dr.amgadrabie@gmail.com.
Comput Biol Chem ; 104: 107768, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2307075
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Experimental Studies / Prognostic study Topics: Variants Limits: Humans Language: English Journal: Comput Biol Chem Journal subject: Biology / Medical Informatics / Chemistry Year: 2023 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Experimental Studies / Prognostic study Topics: Variants Limits: Humans Language: English Journal: Comput Biol Chem Journal subject: Biology / Medical Informatics / Chemistry Year: 2023 Document Type: Article