{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:09:31Z","timestamp":1790392171053,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"46","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemistrySelect"],"published-print":{"date-parts":[[2022,12,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Given the rapid progression of the coronavirus disease 2019 (COVID\u201019) pandemic, an ultrafast response was urgently required to handle this major public crisis. To contain the pandemic, investments are required to develop diagnostic tests, prophylactic vaccines, and novel therapies. Lately, nucleoside analog (NA) antivirals topped the scene as top options for the treatment of COVID\u201019 caused by the severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) infections. Meanwhile, the continuous generation of new lineages of the SARS\u2010CoV\u20102 Omicron variant caused a new challenge in the persistent COVID\u201019 battle. Hitting the two crucial SARS\u2010CoV\u20102 enzymes RNA\u2010dependent RNA polymerase (RdRp) and 3\u2019\u2010to\u20105\u2019 exoribonuclease (ExoN) collectively together using only one single ligand is a very successful new approach to stop SARS\u2010CoV\u20102 multiplication and combat COVID\u201019 irrespective of the SARS\u2010CoV\u20102 variant type because RdRps and ExoNs are broadly conserved among all SARS\u2010CoV\u20102 strains. Herein, the current comprehensive study investigated most NAs libraries, searching for the most ideal drug candidates expectedly able to perfectly act through this double tactic. Gradual computational filtration gave rise to six different promising NAs, which are riboprine, forodesine, tecadenoson, nelarabine, vidarabine, and maribavir, respectively. Further biological assessment proved for the first time, using the\n                    <jats:italic>in\u2005vitro<\/jats:italic>\n                    anti\u2010RdRp\/ExoN and anti\u2010SARS\u2010CoV\u20102 bioassays, that riboprine and forodesine, among all the six tested NAs, are able to powerfully inhibit the replication of the new virulent strains of SARS\u2010CoV\u20102 with extremely minute\n                    <jats:italic>in\u2005vitro<\/jats:italic>\n                    anti\u2010RdRp and anti\u2010SARS\u2010CoV\u20102 EC\n                    <jats:sub>50<\/jats:sub>\n                    values of about 0.22 and 0.49\u2005\u03bcM for riboprine and about 0.25 and 0.73\u2005\u03bcM for forodesine, respectively, surpassing both remdesivir and the new anti\u2010COVID\u201019 drug molnupiravir. The prior\n                    <jats:italic>in\u2009silico<\/jats:italic>\n                    data supported these biochemical findings, suggesting that riboprine and forodesine molecules strongly hit the key catalytic pockets of the SARS\u2010CoV\u20102 (Omicron variant) RdRp\u2032s and ExoN\u2032s main active sites. Additionally, the ideal pharmacophoric features of riboprine and forodesine molecules render them typical dual\u2010action inhibitors of SARS\u2010CoV\u20102 replication and proofreading, with their relatively flexible structures open for diverse types of chemical derivatization. In Brief, the current important results of this comprehensive study revealed the interesting repurposing potentials of, mainly, the two nucleosides riboprine and forodesine to effectively shut down the polymerase\/exoribonuclease\u2010RNA nucleotides interactions of the SARS\u2010CoV\u20102 Omicron variant and consequently treat COVID\u201019 infections, motivating us to rapidly begin the two drugs\u2032 broad preclinical\/clinical anti\u2010COVID\u201019 bioevaluations, hoping to combine both drugs soon in the COVID\u201019 treatment protocols.\n                  <\/jats:p>","DOI":"10.1002\/slct.202201912","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T12:09:16Z","timestamp":1670501356000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A Series of Adenosine Analogs as the First Efficacious Anti\u2010SARS\u2010CoV\u20102 Drugs against the B.1.1.529.4 Lineage: A Preclinical Repurposing Research Study"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3681-114X","authenticated-orcid":false,"given":"Amgad M.","family":"Rabie","sequence":"first","affiliation":[{"name":"Dr. Amgad Rabie's Research Lab. for Drug Discovery (DARLD)  35511 Mansoura Dakahlia Governorate Egypt"},{"name":"Head of Drug Discovery &amp; Clinical Research Department Dikernis General Hospital (DGH)  Magliss El-Madina Street Dikernis 35744 Dikernis Dakahlia Governorate Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1682-5547","authenticated-orcid":false,"given":"Mohnad","family":"Abdalla","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-020-02476-9"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-020-0169-8"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2021.174233"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crphar.2021.100055"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107831"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-021-05773-w"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(21)00222-8"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n2713"},{"key":"e_1_2_8_9_1","doi-asserted-by":"crossref","unstructured":"M. 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