{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:53:41Z","timestamp":1790636021407,"version":"4.1.0"},"reference-count":75,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T00:00:00Z","timestamp":1612828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Nature Science Foundation of China","award":["31871324,81730064, 31571368"],"award-info":[{"award-number":["31871324,81730064, 31571368"]}]},{"name":"the Natural Science Foundation of Hunan Province","award":["2018JJ3713"],"award-info":[{"award-number":["2018JJ3713"]}]},{"name":"the Hunan Youth Elite Project","award":["2018RS3006"],"award-info":[{"award-number":["2018RS3006"]}]},{"name":"the National Science and Technology Major Project","award":["2018ZX10715004"],"award-info":[{"award-number":["2018ZX10715004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Nucleoside and nucleotide analogues are essential antivirals in the treatment of infectious diseases such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus (HSV), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV). To celebrate the 80th birthday of Prof. Dr. Erik De Clercq on 28 March 2021, this review provides an overview of his contributions to eight approved nucleos(t)ide drugs: (i) three adenosine nucleotide analogues, namely tenofovir disoproxil fumarate (Viread\u00ae) and tenofovir alafenamide (Vemlidy\u00ae) against HIV and HBV infections and adefovir dipivoxil (Hepsera\u00ae) against HBV infections; (ii) two thymidine nucleoside analogues, namely brivudine (Zostex\u00ae) against HSV-1 and VZV infections and stavudine (Zerit\u00ae) against HIV infections; (iii) two guanosine analogues, namely valacyclovir (Valtrex\u00ae, Zelitrex\u00ae) against HSV and VZV and rabacfosadine (Tanovea\u00ae-CA1) for the treatment of lymphoma in dogs; and (iv) one cytidine nucleotide analogue, namely cidofovir (Vistide\u00ae) for the treatment of HCMV retinitis in AIDS patients. Although adefovir dipivoxil, stavudine, and cidofovir are virtually discontinued for clinical use, tenofovir disoproxil fumarate and tenofovir alafenamide remain the most important antivirals against HIV and HBV infections worldwide. Overall, the broad-spectrum antiviral potential of nucleos(t)ide analogues supports their development to treat or prevent current and emerging infectious diseases worldwide.<\/jats:p>","DOI":"10.3390\/molecules26040923","type":"journal-article","created":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T02:08:12Z","timestamp":1613268492000},"page":"923","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Drug Discovery of Nucleos(t)ide Antiviral Agents: Dedicated to Prof. Dr. Erik De Clercq on Occasion of His 80th Birthday"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8852-034X","authenticated-orcid":false,"given":"Guangdi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011, China"},{"name":"Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha 410078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2868-0787","authenticated-orcid":false,"given":"Tingting","family":"Yue","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha 410078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha 410078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3706-7404","authenticated-orcid":false,"given":"Weijie","family":"Gu","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry, Rega Institute for Medicinal Research, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8889-3621","authenticated-orcid":false,"given":"Ling-Jie","family":"Gao","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry, Rega Institute for Medicinal Research, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Seley-Radtke, K. (2020). Discovery, Design, Synthesis, and Application of Nucleoside\/Nucleotides. Molecules, 25.","DOI":"10.3390\/molecules25071526"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Khandazhinskaya, A.L., Matyugina, E.S., Solyev, P.N., Wilkinson, M., Buckheit, K.W., Buckheit, R.W., Chernousova, L.N., Smirnova, T.G., Andreevskaya, S.N., and Alzahrani, K.J. (2019). Investigation of 5\u2032-Norcarbocyclic Nucleoside Analogues as Antiprotozoal and Antibacterial Agents. Molecules, 24.","DOI":"10.3390\/molecules24193433"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1128\/CMR.00102-15","article-title":"Approved Antiviral Drugs over the Past 50 Years","volume":"29","author":"Li","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/nrd4010","article-title":"Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases","volume":"12","author":"Jordheim","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.antiviral.2018.04.004","article-title":"The evolution of nucleoside analogue antivirals: A review for chemists and non-chemists. Part 1: Early structural modifications to the nucleoside scaffold","volume":"154","author":"Yates","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.antiviral.2018.11.016","article-title":"The evolution of antiviral nucleoside analogues: A review for chemists and non-chemists. Part II: Complex modifications to the nucleoside scaffold","volume":"162","author":"Yates","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Yates, M.K., Chatterjee, P., Flint, M., Arefeayne, Y., Makuc, D., Plavec, J., Spiropoulou, C.F., and Seley-Radtke, K.L. (2019). Probing the Effects of Pyrimidine Functional Group Switches on Acyclic Fleximer Analogues for Antiviral Activity. Molecules, 24.","DOI":"10.3390\/molecules24173184"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Venkatesham, A., Pillalamarri, S.R., De Wit, F., Lescrinier, E., Debyser, Z., and Van Aerschot, A. (2019). Propargylated Purine Deoxynucleosides: New Tools for Fluorescence Imaging Strategies. Molecules, 24.","DOI":"10.3390\/molecules24030468"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Dentmon, Z.W., Kaiser, T.M., and Liotta, D.C. (2020). Synthesis and Antiviral Activity of a Series of 2\u2032-C-Methyl-4\u2032-thionucleoside Monophosphate Prodrugs. Molecules, 25.","DOI":"10.3390\/molecules25215165"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Geant, P.Y., Uttaro, J.P., P\u00e9rigaud, C., and Math\u00e9, C. (2020). Synthesis and Antiviral Evaluation of 3\u2032-Fluoro-5\u2032-norcarbocyclic Nucleoside Phosphonates Bearing Uracil and Cytosine as Potential Antiviral Agents. Molecules, 25.","DOI":"10.3390\/molecules25163708"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kasthuri, M., Li, C., Verma, K., Russell, O.O., Dickson, L., McCormick, L., Bassit, L., Amblard, F., and Schinazi, R.F. (2020). Synthesis of 4\u2032-Substituted-2\u2032-Deoxy-2\u2032-\u03b1-Fluoro Nucleoside Analogs as Potential Antiviral Agents. Molecules, 25.","DOI":"10.3390\/molecules25061258"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Maslova, A.A., Matyugina, E.S., Snoeck, R., Andrei, G., Kochetkov, S.N., Khandazhinskaya, A.L., and Novikov, M.S. (2020). Uracil-Containing Heterodimers of a New Type: Synthesis and Study of Their Anti-Viral Properties. Molecules, 25.","DOI":"10.3390\/molecules25153350"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bassetto, M., Cima, C.M., Basso, M., Salerno, M., Schwarze, F., Friese, D., Bugert, J.J., and Brancale, A. (2020). Novel Nucleoside Analogues as Effective Antiviral Agents for Zika Virus Infections. Molecules, 25.","DOI":"10.3390\/molecules25204813"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Papadakis, G., Gerasi, M., Snoeck, R., Marakos, P., Andrei, G., Lougiakis, N., and Pouli, N. (2020). Synthesis of New Imidazopyridine Nucleoside Derivatives Designed as Maribavir Analogues. Molecules, 25.","DOI":"10.3390\/molecules25194531"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1021\/acs.jmedchem.5b01157","article-title":"C-Nucleosides to Be Revisited","volume":"59","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_16","first-page":"1","article-title":"Mozobil\u00ae (Plerixafor, AMD3100), 10 years after its approval by the US Food and Drug Administration","volume":"27","year":"2019","journal-title":"Antivir. Chem. Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"De Clercq, E. (2015). AMD3100\/CXCR4 Inhibitor. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00276"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1080\/17425255.2020.1711884","article-title":"Clinical significance of chemokine receptor antagonists","volume":"16","author":"Miao","year":"2020","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1016\/j.bcp.2008.12.014","article-title":"The AMD3100 story: The path to the discovery of a stem cell mobilizer (Mozobil)","volume":"77","year":"2009","journal-title":"Biochem. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1021\/jm900932g","article-title":"Highlights in the discovery of antiviral drugs: A personal retrospective","volume":"53","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1002\/med.21340","article-title":"Curious discoveries in antiviral drug development: The role of serendipity","volume":"35","year":"2015","journal-title":"Med. Res. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/d41573-020-00016-0","article-title":"Therapeutic options for the 2019 novel coronavirus (2019-nCoV)","volume":"19","author":"Li","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Parang, K., El-Sayed, N.S., Kazeminy, A.J., and Tiwari, R.K. (2020). Comparative Antiviral Activity of Remdesivir and Anti-HIV Nucleoside Analogs Against Human Coronavirus 229E (HCoV-229E). Molecules, 25.","DOI":"10.3390\/molecules25102343"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.2147\/DDDT.S254754","article-title":"Danoprevir for the Treatment of Hepatitis C Virus Infection: Design, Development, and Place in Therapy","volume":"14","author":"Miao","year":"2020","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1007\/s12072-020-10015-3","article-title":"Rapidly decreased HBV RNA predicts responses of pegylated interferons in HBeAg-positive patients: A longitudinal cohort study","volume":"14","author":"Zhang","year":"2020","journal-title":"Hepatol. Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1128\/AAC.37.2.332","article-title":"Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: Potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine","volume":"37","author":"Balzarini","year":"1993","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1126\/science.270.5239.1197","article-title":"Prevention of SIV infection in macaques by (R)-9-(2-phosphonylmethoxypropyl)adenine","volume":"270","author":"Tsai","year":"1995","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bcp.2016.04.015","article-title":"Tenofovir alafenamide (TAF) as the successor of tenofovir disoproxil fumarate (TDF)","volume":"119","year":"2016","journal-title":"Biochem. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1080\/17425255.2019.1673367","article-title":"Current and emerging non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV-1 treatment","volume":"15","author":"Wang","year":"2019","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.bcp.2017.11.023","article-title":"Role of tenofovir alafenamide (TAF) in the treatment and prophylaxis of HIV and HBV infections","volume":"153","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1097\/QAI.0000000000000225","article-title":"Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: A randomized phase 2 study","volume":"67","author":"Sax","year":"2014","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1056\/NEJMoa1011205","article-title":"Preexposure chemoprophylaxis for HIV prevention in men who have sex with men","volume":"363","author":"Grant","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.jhep.2020.07.038","article-title":"Similar risk of hepatocellular carcinoma during long-term entecavir or tenofovir therapy in Caucasian patients with chronic hepatitis B","volume":"74","author":"Wen","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/S2468-1253(16)30107-8","article-title":"GS-US-320-0108 Investigators, Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: A randomised, double-blind, phase 3, non-inferiority trial","volume":"1","author":"Buti","year":"2016","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.jhep.2017.11.039","article-title":"Investigators, 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection","volume":"68","author":"Agarwal","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e01064","DOI":"10.1128\/AAC.01064-18","article-title":"No Resistance to Tenofovir Alafenamide Detected through 96 Weeks of Treatment in Patients with Chronic Hepatitis B Infection","volume":"62","author":"Cathcart","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1007\/s00535-020-01680-0","article-title":"Adverse events of nucleos(t)ide analogues for chronic hepatitis B: A systematic review","volume":"55","author":"Mendes","year":"2020","journal-title":"J. Gastroenterol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/rmv.624","article-title":"The history of antiretrovirals: Key discoveries over the past 25 years","volume":"19","year":"2009","journal-title":"Rev. Med. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1056\/NEJMoa021812","article-title":"Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B","volume":"348","author":"Hadziyannis","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1056\/NEJMoa020681","article-title":"Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B","volume":"348","author":"Marcellin","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1056\/NEJMoa0802878","article-title":"Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B","volume":"359","author":"Marcellin","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/S0140-6736(12)61425-1","article-title":"Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: A 5-year open-label follow-up study","volume":"381","author":"Marcellin","year":"2013","journal-title":"Lancet"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2017). EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J. Hepatol., 67, 370\u2013398.","DOI":"10.1016\/j.jhep.2017.03.021"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1002\/hep.29800","article-title":"Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance","volume":"67","author":"Terrault","year":"2018","journal-title":"Hepatology"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Higashi-Kuwata, N., Hayashi, S., Kumamoto, H., Ogata-Aoki, H., Das, D., Venzon, D., Hattori, S.I., Bulut, H., Hashimoto, M., and Otagiri, M. (2020). Identification of a novel long-acting 4\u2032-modified nucleoside reverse transcriptase inhibitor against HBV. J. Hepatol.","DOI":"10.1016\/j.jhep.2020.12.006"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Eyer, L., Svoboda, P., Balvan, J., Vi\u010dar, T., Raudenska, M., \u0160tef\u00e1nik, M., Haviernik, J., Huvarova, I., Strakova, P., and Rudolf, I. (2021). Broad-Spectrum Antiviral Activity of 3\u2032-Deoxy-3\u2032-Fluoroadenosine against Emerging Flaviviruses. Antimicrob. Agents Chemother., 65.","DOI":"10.1128\/AAC.01522-20"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Tanase, C.I., Draghici, C., Hanganu, A., Pintilie, L., Maganu, M., Volobueva, A., Sinegubova, E., Zarubaev, V.V., Neyts, J., and Jochmans, D. (2019). New HSV-1 Anti-Viral 1\u2032-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Fragment as a Glycoside Moiety. Molecules, 24.","DOI":"10.3390\/ecsoc-24-08367"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-pharmtox-010510-100228","article-title":"A 40-year journey in search of selective antiviral chemotherapy","volume":"51","year":"2011","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.apsb.2015.09.001","article-title":"An Odyssey in antiviral drug development-50 years at the Rega Institute: 1964\u20132014","volume":"5","year":"2015","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1073\/pnas.76.6.2947","article-title":"(E)-5-(2-Bromovinyl)-2\u2032-deoxyuridine: A potent and selective anti-herpes agent","volume":"76","author":"Descamps","year":"1979","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"De Clercq, E., Degreef, H., Wildiers, J., De Jonge, G., Drochmans, A., Descamps, J., and De Somer, P. (1980). Oral (E)-5-(2-bromovinyl)-2\u2032-deoxyuridine in severe herpes zoster. Br. Med. J., 281.","DOI":"10.1136\/bmj.281.6249.1178"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1128\/AAC.49.3.1081-1086.2005","article-title":"Susceptibilities of several clinical varicella-zoster virus (VZV) isolates and drug-resistant VZV strains to bicyclic furano pyrimidine nucleosides","volume":"49","author":"Andrei","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/0006-291X(87)90460-8","article-title":"Both 2\u2032,3\u2032-dideoxythymidine and its 2\u2032,3\u2032-unsaturated derivative (2\u2032,3\u2032-dideoxythymidinene) are potent and selective inhibitors of human immunodeficiency virus replication in vitro","volume":"142","author":"Baba","year":"1987","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Bertoletti, N., Chan, A.H., Schinazi, R.F., and Anderson, K.S. (2020). Post-Catalytic Complexes with Emtricitabine or Stavudine and HIV-1 Reverse Transcriptase Reveal New Mechanistic Insights for Nucleotide Incorporation and Drug Resistance. Molecules, 25.","DOI":"10.3390\/molecules25204868"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1021\/jm00358a029","article-title":"Synthesis and antiviral activity of water-soluble esters of acyclovir [9-[(2-hydroxyethoxy)methyl]guanine]","volume":"26","author":"Colla","year":"1983","journal-title":"J. Med. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1002\/med.20128","article-title":"The discovery of antiviral agents: Ten different compounds, ten different stories","volume":"28","year":"2008","journal-title":"Med. Res. Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1001\/archopht.1984.01040030118049","article-title":"Topical treatment of experimental herpes simplex keratouveitis with 2\u2032-O-glycylacyclovir. A water-soluble ester of acyclovir","volume":"102","author":"Maudgal","year":"1984","journal-title":"Arch. Ophthalmol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"S40","DOI":"10.1086\/342966","article-title":"Valacyclovir for herpes simplex virus infection: Long-term safety and sustained efficacy after 20 years\u2019 experience with acyclovir","volume":"186","author":"Tyring","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1097\/QCO.0000000000000368","article-title":"Congenital cytomegalovirus infection: Management update","volume":"30","author":"Khalil","year":"2017","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1111\/tri.13085","article-title":"Impact of antiviral prophylaxis in adults Epstein-Barr Virus-seronegative kidney recipients on early and late post-transplantation lymphoproliferative disorder onset: A retrospective cohort study","volume":"31","author":"Ville","year":"2018","journal-title":"Transpl. Int."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0166-3542(87)80004-9","article-title":"Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines","volume":"8","author":"Sakuma","year":"1987","journal-title":"Antiviral. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"21966","DOI":"10.1074\/jbc.273.34.21966","article-title":"Incorporation and excision of 9-(2-phosphonylmethoxyethyl)guanine (PMEG) by DNA polymerase delta and epsilon in vitro","volume":"273","author":"Kramata","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_63","first-page":"195","article-title":"9-(2-phosphonylmethoxyethyl)-N6-cyclopropyl-2,6-diaminopurine: A novel prodrug of 9-(2-phosphonylmethoxyethyl)guanine with improved antitumor efficacy and selectivity in choriocarcinoma-bearing rats","volume":"11","author":"Naesens","year":"1999","journal-title":"Oncol. Res. Featur. Preclin. Clin. Cancer Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.bcp.2018.05.010","article-title":"Tanovea(R) for the treatment of lymphoma in dogs","volume":"154","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.1158\/1078-0432.CCR-07-2061","article-title":"GS-9219\u2014A novel acyclic nucleotide analogue with potent antineoplastic activity in dogs with spontaneous non-Hodgkin\u2019s lymphoma","volume":"14","author":"Reiser","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.bcp.2011.03.027","article-title":"The clinical potential of the acyclic (and cyclic) nucleoside phosphonates: The magic of the phosphonate bond","volume":"82","year":"2011","journal-title":"Biochem. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.bcp.2012.03.024","article-title":"Where rilpivirine meets with tenofovir, the start of a new anti-HIV drug combination era","volume":"84","year":"2012","journal-title":"Biochem. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Andrei, G., Trompet, E., and Snoeck, R. (2019). Novel Therapeutics for Epstein\u2014Barr Virus. Molecules, 24.","DOI":"10.3390\/molecules24050997"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1002\/jmv.21165","article-title":"Treatment of locally recurrent Epstein-Barr virus-associated nasopharyngeal carcinoma using the anti-viral agent cidofovir","volume":"80","author":"Yoshizaki","year":"2008","journal-title":"J. Med. Virol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Malin, J.J., Su\u00e1rez, I., Priesner, V., Fatkenheuer, G., and Rybniker, J. (2021). Remdesivir against COVID-19 and Other Viral Diseases. Clin. Microbiol. Rev., 34.","DOI":"10.1128\/CMR.00162-20"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"11296","DOI":"10.18632\/aging.103535","article-title":"Clinical characteristics of older and younger patients infected with SARS-CoV-2","volume":"12","author":"Zhou","year":"2020","journal-title":"Aging"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Jiang, C., Wang, Y., Hu, M., Wen, L., Wen, C., Wang, Y., Zhu, W., Tai, S., Jiang, Z., and Xiao, K. (2020). Antibody seroconversion in asymptomatic and symptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin. Transl. Immunol., 9.","DOI":"10.1002\/cti2.1182"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"27","DOI":"10.18632\/aging.202456","article-title":"Mortality risk of COVID-19 in elderly males with comorbidities: A multi-country study","volume":"13","author":"Li","year":"2020","journal-title":"Aging"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Yousefi, H., Mashouri, L., Okpechi, S.C., Alahari, N., and Alahari, S.K. (2021). Repurposing existing drugs for the treatment of COVID-19\/SARS-CoV-2 infection: A review describing drug mechanisms of action. Biochem. Pharmacol., 183.","DOI":"10.1016\/j.bcp.2020.114296"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/2040206618758524","article-title":"Addressing the selectivity and toxicity of antiviral nucleosides","volume":"26","author":"Feng","year":"2018","journal-title":"Antivir. Chem. Chemother."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/4\/923\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:22:08Z","timestamp":1760160128000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/4\/923"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,9]]},"references-count":75,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["molecules26040923"],"URL":"https:\/\/doi.org\/10.3390\/molecules26040923","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,9]]}}}