{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T06:29:59Z","timestamp":1762928999108,"version":"build-2065373602"},"reference-count":121,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The COVID-19 pandemic has flared across every part of the globe and affected populations from different age groups differently. People aged from 40 to 80 years or older are at an increased risk of morbidity and mortality due to COVID-19. Therefore, there is an urgent requirement to develop therapeutics to decrease the risk of the disease in the aged population. Over the last few years, several prodrugs have demonstrated significant anti-SARS-CoV-2 effects in in vitro assays, animal models, and medical practice. Prodrugs are used to enhance drug delivery by improving pharmacokinetic parameters, decreasing toxicity, and attaining site specificity. This article discusses recently explored prodrugs such as remdesivir, molnupiravir, favipiravir, and 2-deoxy-D-glucose (2-DG) and their implications in the aged population, as well as investigating recent clinical trials.<\/jats:p>","DOI":"10.3390\/molecules28052332","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T01:43:00Z","timestamp":1677807780000},"page":"2332","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Potential Anti-SARS-CoV-2 Prodrugs Activated by Phosphorylation and Their Role in the Aged Population"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7701-8597","authenticated-orcid":false,"given":"Vivek P.","family":"Chavda","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, L. M. College of Pharmacy, Ahmedabad 380008, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Divya","family":"Teli","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, L. M. College of Pharmacy, Ahmedabad 380009, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pankti C.","family":"Balar","sequence":"additional","affiliation":[{"name":"Pharmacy Section, L. M. College of Pharmacy, Ahmedabad 380008, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dixa","family":"Vaghela","sequence":"additional","affiliation":[{"name":"Pharmacy Section, L. M. College of Pharmacy, Ahmedabad 380008, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hetvi K.","family":"Solanki","sequence":"additional","affiliation":[{"name":"Pharmacy Section, L. M. College of Pharmacy, Ahmedabad 380008, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akta","family":"Vaishnav","sequence":"additional","affiliation":[{"name":"Pharmacy Section, L. M. College of Pharmacy, Ahmedabad 380008, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8106-9066","authenticated-orcid":false,"given":"Lalitkumar","family":"Vora","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"631736","DOI":"10.3389\/fmicb.2020.631736","article-title":"Pandemics Throughout History","volume":"11","author":"Piret","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1016\/j.drudis.2021.07.021","article-title":"Intranasal Vaccines for SARS-CoV-2: From Challenges to Potential in COVID-19 Management","volume":"26","author":"Chavda","year":"2021","journal-title":"Drug Discov. Today"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chavda, V.P., Soni, S., Vora, L.K., Soni, S., Khadela, A., and Ajabiya, J. (2022). MRNA-Based Vaccines and Therapeutics for COVID-19 and Future Pandemics. Vaccines, 10.","DOI":"10.3390\/vaccines10122150"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"961198","DOI":"10.3389\/fimmu.2022.961198","article-title":"Fast-Track Development of Vaccines for SARS-CoV-2: The Shots That Saved the World","volume":"13","author":"Chavda","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_5","unstructured":"(2022, September 23). WHO Coronavirus (COVID-19) Dashboard. Available online: https:\/\/covid19.who.int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1021\/acs.oprd.0c00233","article-title":"Quest for a COVID-19 Cure by Repurposing Small-Molecule Drugs: Mechanism of Action, Clinical Development, Synthesis at Scale, and Outlook for Supply","volume":"24","author":"Hughes","year":"2020","journal-title":"Org. Process Res. Dev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41392-022-01249-8","article-title":"Small Molecules in the Treatment of COVID-19","volume":"7","author":"Lei","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3803","DOI":"10.2174\/0929867327666200721161840","article-title":"Current Trends and Future Approaches in Small-Molecule Therapeutics for COVID-19","volume":"28","author":"Laws","year":"2021","journal-title":"Curr. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1038\/s41467-022-29413-2","article-title":"Development of Optimized Drug-like Small Molecule Inhibitors of the SARS-CoV-2 3CL Protease for Treatment of COVID-19","volume":"13","author":"Liu","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"671498","DOI":"10.3389\/fphar.2021.671498","article-title":"Traditional Herbal Medicines, Bioactive Metabolites, and Plant Products Against COVID-19: Update on Clinical Trials and Mechanism of Actions","volume":"12","author":"Alam","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"599079","DOI":"10.3389\/fmolb.2020.599079","article-title":"In Silico Screening of Natural Compounds as Potential Inhibitors of SARS-CoV-2 Main Protease and Spike RBD: Targets for COVID-19","volume":"7","author":"Teli","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"100141","DOI":"10.1016\/j.metop.2021.100141","article-title":"Herbal Medicine Use for the Management of COVID-19: A Review Article","volume":"12","author":"Demeke","year":"2021","journal-title":"Metab. Open"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.2147\/IDR.S331434","article-title":"Traditional Medicine Practice in the Context of COVID-19 Pandemic: Community Claim in Jimma Zone, Oromia, Ethiopia","volume":"14","author":"Melaku","year":"2021","journal-title":"Infect. Drug Resist."},{"key":"ref_14","unstructured":"(2022, December 07). COVID-19 Vaccine Resource Center. Available online: https:\/\/www.nejm.org\/covid-vaccine."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1093\/cid\/ciab079","article-title":"The Impact of Vaccination on Coronavirus Disease 2019 (COVID-19) Outbreaks in the United States","volume":"73","author":"Moghadas","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/s41418-020-00720-9","article-title":"COVID-19 Vaccines: Where We Stand and Challenges Ahead","volume":"28","author":"Forni","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"809244","DOI":"10.3389\/fimmu.2021.809244","article-title":"SARS-CoV-2 Variants, Vaccines, and Host Immunity","volume":"12","author":"Mistry","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1056\/NEJMsr2105280","article-title":"SARS-CoV-2 Variants and Vaccines","volume":"385","author":"Krause","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/s41586-021-03777-9","article-title":"Reduced Sensitivity of SARS-CoV-2 Variant Delta to Antibody Neutralization","volume":"596","author":"Planas","year":"2021","journal-title":"Nature"},{"key":"ref_20","unstructured":"(2022, November 25). The Effects of Virus Variants on COVID-19 Vaccines. Available online: https:\/\/www.who.int\/news-room\/feature-stories\/detail\/the-effects-of-virus-variants-on-covid-19-vaccines."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Chavda, V.P., and Apostolopoulos, V. (2022). Is Booster Dose Strategy Sufficient for Omicron Variant of SARS-CoV-2?. Vaccines, 10.","DOI":"10.3390\/vaccines10030367"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1080\/14760584.2022.2044800","article-title":"Global Impact of Delta plus Variant and Vaccination","volume":"21","author":"Chavda","year":"2022","journal-title":"Expert Rev. Vaccines"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Chavda, V.P., Bezbaruah, R., Deka, K., Nongrang, L., and Kalita, T. (2022). The Delta and Omicron Variants of SARS-CoV-2: What We Know So Far. Vaccines, 10.","DOI":"10.3390\/vaccines10111926"},{"key":"ref_24","unstructured":"Mohapatra, S.S., Ranjan, S., Dasgupta, N., Mishra, R.K., and Thomas, S. (2019). Applications of Targeted Nano Drugs and Delivery Systems, Elsevier. Chapter 4."},{"key":"ref_25","unstructured":"Mohapatra, S.S., Ranjan, S., Dasgupta, N., Mishra, R.K., and Thomas, S. (2019). Applications of Targeted Nano Drugs and Delivery Systems, Elsevier. Chapter 1."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1002\/jmv.27517","article-title":"Broad-spectrum Prodrugs with Anti-SARS-CoV-2 Activities: Strategies, Benefits, and Challenges","volume":"94","author":"Wang","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nrd.2018.46","article-title":"The Expanding Role of Prodrugs in Contemporary Drug Design and Development","volume":"17","author":"Rautio","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_28","first-page":"1","article-title":"Molnupiravir, Favipiravir and Other Antiviral Drugs with Proposed Potentials for Management of COVID-19: A Concern on Antioxidant Aspect","volume":"13","author":"Yasri","year":"2022","journal-title":"Int. J. Biochem. Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"112517","DOI":"10.1016\/j.biopha.2021.112517","article-title":"RdRp Inhibitors and COVID-19: Is Molnupiravir a Good Option?","volume":"146","author":"Hashemian","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1007\/s10529-022-03259-6","article-title":"A Novel Property of Hexokinase Inhibition by Favipiravir and Proposed Advantages over Molnupiravir and 2 Deoxy d Glucose in Treating COVID-19","volume":"44","author":"Kulkarni","year":"2022","journal-title":"Biotechnol. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"899633","DOI":"10.3389\/fphar.2022.899633","article-title":"2-Deoxy-D-Glucose and Its Derivatives for the COVID-19 Treatment: An Update","volume":"13","author":"Huang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1021\/acscentsci.0c00489","article-title":"Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19","volume":"6","author":"Eastman","year":"2020","journal-title":"ACS Cent. Sci."},{"key":"ref_33","unstructured":"Center for Drug Evaluation and Research (2021). FDA\u2019s Approval of Veklury (Remdesivir) for the Treatment of COVID-19\u2014The Science of Safety and Effectiveness, FDA."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Yang, L., and Wang, Z. (2021). Natural Products, Alone or in Combination with FDA-Approved Drugs, to Treat COVID-19 and Lung Cancer. Biomedicines, 9.","DOI":"10.3390\/biomedicines9060689"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"12417","DOI":"10.1039\/D0NJ02656E","article-title":"GS-5734: A Potentially Approved Drug by FDA against SARS-Cov-2","volume":"44","author":"Wang","year":"2020","journal-title":"New J. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"113862","DOI":"10.1016\/j.ejmech.2021.113862","article-title":"Synthesis and Antiviral Activity of Fatty Acyl Conjugates of Remdesivir against Severe Acute Respiratory Syndrome Coronavirus 2 and Ebola Virus","volume":"226","author":"Jureka","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Li, Y., Liu, M., Yan, Y., Wang, Z., Dai, Q., Yang, X., Guo, X., Li, W., Chen, X., and Cao, R. (2022). Molnupiravir and Its Active Form, EIDD-1931, Show Potent Antiviral Activity against Enterovirus Infections In Vitro and In Vivo. Viruses, 14.","DOI":"10.3390\/v14061142"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.3389\/fphar.2020.01013","article-title":"Turning the Tide: Natural Products and Natural-Product-Inspired Chemicals as Potential Counters to SARS-CoV-2 Infection","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"103595","DOI":"10.1016\/j.ebiom.2021.103595","article-title":"The Combined Treatment of Molnupiravir and Favipiravir Results in a Potentiation of Antiviral Efficacy in a SARS-CoV-2 Hamster Infection Model","volume":"72","author":"Abdelnabi","year":"2021","journal-title":"EBioMedicine"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s40265-022-01684-5","article-title":"Molnupiravir: First Approval","volume":"82","author":"Syed","year":"2022","journal-title":"Drugs"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.mjafi.2020.08.004","article-title":"Favipiravir: A New and Emerging Antiviral Option in COVID-19","volume":"76","author":"Agrawal","year":"2020","journal-title":"Med. J. Armed. India"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3741","DOI":"10.1128\/JVI.02346-12","article-title":"T-705 (Favipiravir) Induces Lethal Mutagenesis in Influenza A H1N1 Viruses in Vitro","volume":"87","author":"Baranovich","year":"2013","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1016\/j.lfs.2005.07.001","article-title":"2-Deoxyglucose: An Anticancer and Antiviral Therapeutic, but Not Any More a Low Glucose Mimetic","volume":"78","author":"Kang","year":"2006","journal-title":"Life Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3548","DOI":"10.4103\/jfmpc.jfmpc_1338_21","article-title":"Role of 2-Deoxy-D-Glucose (2-DG) in COVID-19 Disease: A Potential Game-Changer","volume":"10","author":"Sahu","year":"2021","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.amsu.2020.12.030","article-title":"Protease Inhibitor GC376 for COVID-19: Lessons Learned from Feline Infectious Peritonitis","volume":"61","author":"Sharun","year":"2021","journal-title":"Ann. Med. Surg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1126\/science.abl4784","article-title":"An Oral SARS-CoV-2 Mpro Inhibitor Clinical Candidate for the Treatment of COVID-19","volume":"374","author":"Owen","year":"2021","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/s42003-022-03090-9","article-title":"Identification of SARS-CoV-2 Inhibitors Targeting Mpro and PLpro Using in-Cell-Protease Assay","volume":"5","author":"Narayanan","year":"2022","journal-title":"Commun. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1111\/hiv.13278","article-title":"RECEDE-C19 study Response to \u2018The Use of Tenofovir in Patients with COVID-19\u2019","volume":"23","author":"Lee","year":"2022","journal-title":"HIV Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/s41467-022-28113-1","article-title":"A Dual Mechanism of Action of AT-527 against SARS-CoV-2 Polymerase","volume":"13","author":"Shannon","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"107831","DOI":"10.1016\/j.intimp.2021.107831","article-title":"Cyanorona-20: The First Potent Anti-SARS-CoV-2 Agent","volume":"98","author":"Rabie","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Jornada, D.H., dos Santos Fernandes, G.F., Chiba, D.E., de Melo, T.R.F., dos Santos, J.L., and Chung, M.C. (2015). The Prodrug Approach: A Successful Tool for Improving Drug Solubility. Molecules, 21.","DOI":"10.3390\/molecules21010042"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nrd2468","article-title":"Prodrugs: Design and Clinical Applications","volume":"7","author":"Rautio","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.cbpa.2009.04.620","article-title":"Prodrugs: Bridging Pharmacodynamic\/Pharmacokinetic Gaps","volume":"13","author":"Testa","year":"2009","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1021\/acs.jmedchem.6b01594","article-title":"Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][Triazin-4-Amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses","volume":"60","author":"Siegel","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1021\/acs.oprd.1c00100","article-title":"Quest for a Cure: Potential Small-Molecule Treatments for COVID-19, Part 2","volume":"25","author":"Hughes","year":"2021","journal-title":"Org. Process Res. Dev."},{"key":"ref_56","unstructured":"Painter, G.R., Guthrie, D.B., Bluemling, G.R., and Natchus, M.G. (2016). N4-Hydroxycytidine and Derivatives and Anti-Viral Uses Related Thereto 2016. (WO2016106050A1), WO Patent."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Benkovics, T., McIntosh, J., Silverman, S., Kong, J., Maligres, P., Itoh, T., Yang, H., Huffman, M., Verma, D., and Pan, W. (2020). Evolving to an Ideal Synthesis of Molnupiravir, an Investigational Treatment for COVID-19. ChemRxiv.","DOI":"10.26434\/chemrxiv.13472373"},{"key":"ref_58","unstructured":"Furuta, Y., and Egawa, H. (2000). Nitrogenous Heterocyclic Carboxamide Derivatives or Salts Thereof and Antiviral Agents Containing Both. (WO2000010569A1), WO Patent."},{"key":"ref_59","unstructured":"Hara, T., Norimatsu, N., Kurushima, H., and Kano, T. (2014). Method for Producing Dichloropyrazine Derivative. (US8835636B2), U.S. Patent."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"8385","DOI":"10.1016\/S0040-4020(00)00691-8","article-title":"The Synthesis of 2-Deoxyglycosides: 1988\u20131999","volume":"56","author":"Marzabadi","year":"2000","journal-title":"Tetrahedron"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3706","DOI":"10.1021\/acs.jmedchem.1c01737","article-title":"A Comprehensive Biological and Synthetic Perspective on 2-Deoxy-d-Glucose (2-DG), A Sweet Molecule with Therapeutic and Diagnostic Potentials","volume":"65","author":"Wijayasinghe","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3686","DOI":"10.1055\/s-0036-1589501","article-title":"Facile Approaches to 2-Deoxy-d-Glucose and 2-Deoxy-\u03b1-d-Glucopyranonucleosides from d-Glucal","volume":"49","author":"Xu","year":"2017","journal-title":"Synthesis"},{"key":"ref_63","unstructured":"(2023, January 12). Indian Patents. 187908: \u201cAn Improved Process for Preparation of 2-Deoxy-D-glucose\u201d. Available online: https:\/\/www.allindianpatents.com\/patents\/187908-an-improved-process-for-preparation-of-2-deoxy-d-glucose."},{"key":"ref_64","unstructured":"(2022, November 26). Commissioner of the FDA Approves First Treatment for COVID-19, Available online: https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-first-treatment-covid-19."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/nature17180","article-title":"Therapeutic Efficacy of the Small Molecule GS-5734 against Ebola Virus in Rhesus Monkeys","volume":"531","author":"Warren","year":"2016","journal-title":"Nature"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1056\/NEJMoa1910993","article-title":"A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics","volume":"381","author":"Mulangu","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1126\/science.abc1560","article-title":"Structural Basis for Inhibition of the RNA-Dependent RNA Polymerase from SARS-CoV-2 by Remdesivir","volume":"368","author":"Yin","year":"2020","journal-title":"Science"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e00162-20","DOI":"10.1128\/CMR.00162-20","article-title":"Remdesivir against COVID-19 and Other Viral Diseases","volume":"34","author":"Malin","year":"2020","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"104541","DOI":"10.1016\/j.antiviral.2019.104541","article-title":"Broad Spectrum Antiviral Remdesivir Inhibits Human Endemic and Zoonotic Deltacoronaviruses with a Highly Divergent RNA Dependent RNA Polymerase","volume":"169","author":"Brown","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.cegh.2020.07.011","article-title":"Remdesivir and Its Antiviral Activity against COVID-19: A Systematic Review","volume":"9","author":"Frediansyah","year":"2021","journal-title":"Clin. Epidemiol. Glob. Health"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"104878","DOI":"10.1016\/j.antiviral.2020.104878","article-title":"In Vitro Evaluation of Antiviral Activity of Single and Combined Repurposable Drugs against SARS-CoV-2","volume":"181","author":"Pizzorno","year":"2020","journal-title":"Antivir. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1001\/jama.2020.16349","article-title":"Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial","volume":"324","author":"Spinner","year":"2020","journal-title":"JAMA"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A Pneumonia Outbreak Associated with a New Coronavirus of Probable Bat Origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1016\/S0140-6736(20)31022-9","article-title":"Remdesivir in Adults with Severe COVID-19: A Randomised, Double-Blind, Placebo-Controlled, Multicentre Trial","volume":"395","author":"Wang","year":"2020","journal-title":"Lancet"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1080\/03007995.2022.2129801","article-title":"Reduced Risk of Death in People with SARS-CoV-2 Infection Treated with Remdesivir: A Nested Case\u2013Control Study","volume":"38","author":"Poliseno","year":"2022","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_76","unstructured":"(2022, December 07). Veklury\u00ae (Remdesivir) Retains Antiviral Activity Against Omicron, Delta and Other Emergent SARS-CoV-2 Variants in Multiple In Vitro Studies. Available online: https:\/\/www.gilead.com\/news-and-press\/press-room\/press-releases\/2022\/2\/veklury-remdesivir-retains-antiviral-activity-against-omicron-delta-and-other-emergent-sarscov2-variants-in-multiple-in-vitro-studies."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Ramos-Rincon, J.-M., L\u00f3pez-Carmona, M.-D., Cobos-Palacios, L., L\u00f3pez-Sampalo, A., Rubio-Rivas, M., Mart\u00edn-Escalante, M.-D., de-Cossio-Tejido, S., Taboada-Mart\u00ednez, M.-L., Mui\u00f1o-Miguez, A., and Areses-Manrique, M. (2022). Remdesivir in Very Old Patients (\u226580 Years) Hospitalized with COVID-19: Real World Data from the SEMI-COVID-19 Registry. J. Clin. Med., 11.","DOI":"10.3390\/jcm11133769"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/all.14657","article-title":"Risk Factors for Severe and Critically Ill COVID-19 Patients: A Review","volume":"76","author":"Gao","year":"2021","journal-title":"Allergy"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","article-title":"Clinical Course and Risk Factors for Mortality of Adult Inpatients with COVID-19 in Wuhan, China: A Retrospective Cohort Study","volume":"395","author":"Zhou","year":"2020","journal-title":"Lancet"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1056\/NEJMoa2116044","article-title":"Molnupiravir for Oral Treatment of COVID-19 in Nonhospitalized Patients","volume":"386","author":"Musungaie","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Mohd, I.., Kumar Arora, M., Asdaq, S.M.B., Khan, S.A., Alaqel, S.I., Alshammari, M.K., Alshehri, M.M., Alshrari, A.S., Mateq Ali, A., and Al-shammeri, A.M. (2021). Discovery, Development, and Patent Trends on Molnupiravir: A Prospective Oral Treatment for COVID-19. Molecules, 26.","DOI":"10.3390\/molecules26195795"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"855496","DOI":"10.3389\/fimmu.2022.855496","article-title":"Molnupiravir and Its Antiviral Activity Against COVID-19","volume":"13","author":"Tian","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"100770","DOI":"10.1016\/j.jbc.2021.100770","article-title":"Molnupiravir Promotes SARS-CoV-2 Mutagenesis via the RNA Template","volume":"297","author":"Gordon","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/s41594-021-00651-0","article-title":"Mechanism of Molnupiravir-Induced SARS-CoV-2 Mutagenesis","volume":"28","author":"Kabinger","year":"2021","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"6097","DOI":"10.1038\/s41467-021-26354-0","article-title":"COVA1-18 Neutralizing Antibody Protects against SARS-CoV-2 in Three Preclinical Models","volume":"12","author":"Maisonnasse","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"eabb5883","DOI":"10.1126\/scitranslmed.abb5883","article-title":"An Orally Bioavailable Broad-Spectrum Antiviral Inhibits SARS-CoV-2 in Human Airway Epithelial Cell Cultures and Multiple Coronaviruses in Mice","volume":"12","author":"Sheahan","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1093\/infdis\/jiab362","article-title":"Letter to the Editor in Response to Zhou et Al","volume":"224","author":"Troth","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1093\/infdis\/jiab361","article-title":"Molnupiravir Inhibits Replication of the Emerging SARS-CoV-2 Variants of Concern in a Hamster Infection Model","volume":"224","author":"Abdelnabi","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1056\/NEJMc2119407","article-title":"Efficacy of Antibodies and Antiviral Drugs against COVID-19 Omicron Variant","volume":"386","author":"Takashita","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e160108","DOI":"10.1172\/jci.insight.160108","article-title":"Molnupiravir Inhibits SARS-CoV-2 Variants Including Omicron in the Hamster Model","volume":"7","author":"Rosenke","year":"2022","journal-title":"JCI Insight"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"5582","DOI":"10.1002\/jmv.28011","article-title":"Safety and Efficacy of Molnupiravir in SARS-CoV-2-infected Patients: A Real-life Experience","volume":"94","author":"Colpani","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1007\/s43440-022-00408-6","article-title":"Real-World Experience with Molnupiravir during the Period of SARS-CoV-2 Omicron Variant Dominance","volume":"74","author":"Flisiak","year":"2022","journal-title":"Pharmacol. Rep."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Gonda, K., Suzuki, K., Kono, K., and Takenoshita, S. (2022). Safety of Oral Administration of Molnupiravir for Hospitalized Elderly People Aged 80 Years Old or Older with COVID-19. Res. Sq., preprint.","DOI":"10.21203\/rs.3.rs-1815198\/v1"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.ijid.2020.10.069","article-title":"Role of Favipiravir in the Treatment of COVID-19","volume":"102","author":"Joshi","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"100086","DOI":"10.1016\/j.crphar.2022.100086","article-title":"Therapeutics for COVID-19 and Post COVID-19 Complications: An Update","volume":"3","author":"Basu","year":"2022","journal-title":"Curr. Res. Pharmacol. Drug Discov."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"11022","DOI":"10.1038\/s41598-021-90551-6","article-title":"The Efficacy and Safety of Favipiravir in Treatment of COVID-19: A Systematic Review and Meta-Analysis of Clinical Trials","volume":"11","author":"Hassanipour","year":"2021","journal-title":"Sci Rep"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/j.eng.2020.03.007","article-title":"Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study","volume":"6","author":"Cai","year":"2020","journal-title":"Engineering"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"101703","DOI":"10.1016\/j.eclinm.2022.101703","article-title":"Favipiravir in Early Symptomatic COVID-19, a Randomised Placebo-Controlled Trial","volume":"54","author":"McMahon","year":"2022","journal-title":"eClinicalMedicine"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.ijid.2020.11.142","article-title":"Efficacy and Safety of Favipiravir, an Oral RNA-Dependent RNA Polymerase Inhibitor, in Mild-to-Moderate COVID-19: A Randomized, Comparative, Open-Label, Multicenter, Phase 3 Clinical Trial","volume":"103","author":"Udwadia","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"103591","DOI":"10.1016\/j.ebiom.2021.103591","article-title":"Clinical Efficacy and Safety Evaluation of Favipiravir in Treating Patients with Severe Fever with Thrombocytopenia Syndrome","volume":"72","author":"Yuan","year":"2021","journal-title":"eBioMedicine"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1007\/s11357-022-00582-8","article-title":"Favipiravir for the Treatment of COVID-19 in Elderly Patients\u2014What Do We Know after 2 Years of COVID-19?","volume":"44","author":"Papp","year":"2022","journal-title":"GeroScience"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1093\/cid\/ciaa1176","article-title":"AVIFAVIR for Treatment of Patients With Moderate Coronavirus Disease 2019 (COVID-19): Interim Results of a Phase II\/III Multicenter Randomized Clinical Trial","volume":"73","author":"Ivashchenko","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1007\/s40121-021-00517-4","article-title":"Efficacy and Safety of Favipiravir in Moderate COVID-19 Pneumonia Patients without Oxygen Therapy: A Randomized, Phase III Clinical Trial","volume":"10","author":"Shinkai","year":"2021","journal-title":"Infect. Dis. Ther."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"300","DOI":"10.3947\/ic.2020.0149","article-title":"Association of Early Favipiravir Use with Reduced COVID-19 Fatality among Hospitalized Patients","volume":"53","author":"Karatas","year":"2021","journal-title":"Infect. Chemother."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1093\/infdis\/jiz656","article-title":"Comparative Effectiveness of Combined Favipiravir and Oseltamivir Therapy Versus Oseltamivir Monotherapy in Critically Ill Patients With Influenza Virus Infection","volume":"221","author":"Wang","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_106","unstructured":"Bureau, E.N. Russian Drug Avifavir Effective against Corona Virus Variants: ChemRar Group. Express Pharma, 2021."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S2055-6640(20)30016-9","article-title":"A Review of the Safety of Favipiravir\u2014A Potential Treatment in the COVID-19 Pandemic?","volume":"6","author":"Pilkington","year":"2020","journal-title":"J. Virus Erad."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s00280-012-2045-1","article-title":"A Phase I Dose-Escalation Trial of 2-Deoxy-D-Glucose Alone or Combined with Docetaxel in Patients with Advanced Solid Tumors","volume":"71","author":"Raez","year":"2013","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_109","first-page":"345","article-title":"Anti-Covid Drug: 2-Deoxy-D-Glucose and Its Mechanism of Action","volume":"3","author":"Samal","year":"2021","journal-title":"Biot. Res. Today"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1039\/D1CB00042J","article-title":"Reactive Oxygen Species, Proinflammatory and Immunosuppressive Mediators Induced in COVID-19: Overlapping Biology with Cancer","volume":"2","author":"Kalyanaraman","year":"2021","journal-title":"RSC Chem. Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"120411","DOI":"10.1016\/j.lfs.2022.120411","article-title":"Glycolytic Inhibitor 2-Deoxy-d-Glucose Attenuates SARS-CoV-2 Multiplication in Host Cells and Weakens the Infective Potential of Progeny Virions","volume":"295","author":"Bhatt","year":"2022","journal-title":"Life Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1099\/jgv.0.001453","article-title":"SARS-Coronavirus-2 Replication in Vero E6 Cells: Replication Kinetics, Rapid Adaptation and Cytopathology","volume":"101","author":"Ogando","year":"2020","journal-title":"J. Gen. Virol."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Balkrishna, A., Thakur, P., Singh, S., Dev, S., Jain, V., Varshney, A., and Sharma, R. (2021). Glucose Antimetabolite 2-Deoxy-D-Glucose and Its Derivative as Promising Candidates for Tackling COVID-19: Insights Derived from in Silico Docking and Molecular Simulations. Authorea, Preprint.","DOI":"10.22541\/au.158567174.40895611\/v2"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s10867-022-09617-9","article-title":"Clinical Effects of 2-DG Drug Restraining SARS-CoV-2 Infection: A Fractional Order Optimal Control Study","volume":"48","author":"Samui","year":"2022","journal-title":"J. Biol. Phys."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1080\/09553002.2020.1818865","article-title":"A Combinatorial Approach of a Polypharmacological Adjuvant 2-Deoxy-D-Glucose with Low Dose Radiation Therapy to Quell the Cytokine Storm in COVID-19 Management","volume":"96","author":"Verma","year":"2020","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_116","unstructured":"(2022, December 09). www.ETHealthworld.com. Indian Drug 2DG Can Reduce Heart Damage by Coronavirus, Find US Researchers\u2014ET HealthWorld. Available online: https:\/\/health.economictimes.indiatimes.com\/news\/pharma\/indian-drug-2dg-can-reduce-heart-damage-by-coronavirus-find-us-researchers\/95382862."},{"key":"ref_117","unstructured":"(2022, November 25). DCGI Approves Anti-COVID Drug Developed by DRDO for Emergency Use, Available online: https:\/\/pib.gov.in\/pib.gov.in\/Pressreleaseshare.aspx?PRID=1717007."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Bhatt, A.N., Shenoy, S., Munjal, S., Chinnadurai, V., Agarwal, A., Vinoth Kumar, A., Shanavas, A., Kanwar, R., and Chandna, S. (2022). 2-Deoxy-d-Glucose as an Adjunct to Standard of Care in the Medical Management of COVID-19: A Proof-of-Concept and Dose-Ranging Randomised Phase II Clinical Trial. BMC Infect. Dis., 22.","DOI":"10.1186\/s12879-022-07642-6"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1080\/1120009X.2022.2099693","article-title":"Early 3-Day Course of Remdesivir in Vaccinated Outpatients with SARS-CoV-2 Infection. A Success Story","volume":"34","author":"Panagopoulos","year":"2022","journal-title":"J. Chemother."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S1473-3099(22)00644-2","article-title":"Molnupiravir versus Placebo in Unvaccinated and Vaccinated Patients with Early SARS-CoV-2 Infection in the UK (AGILE CST-2): A Randomised, Placebo-Controlled, Double-Blind, Phase 2 Trial","volume":"23","author":"Khoo","year":"2023","journal-title":"Lancet Infect. Dis."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Herman, B., Wong, M.C., and Viwattanakulvanid, P. (2022). Vaccination Status, Favipiravir, and Micronutrient Supplementation Roles in Post-COVID Symptoms: A Longitudinal Study. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0271385"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/5\/2332\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:46:34Z","timestamp":1760121994000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/5\/2332"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,2]]},"references-count":121,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["molecules28052332"],"URL":"https:\/\/doi.org\/10.3390\/molecules28052332","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2023,3,2]]}}}