{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T18:37:39Z","timestamp":1787683059953,"version":"build-2784847793"},"reference-count":95,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["enviromicro-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microbial Biotechnology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The rapid global spread of SARS\u2010CoV\u20102 triggered an unprecedented effort to develop effective antivirals. Among the first approved agents was remdesivir, an injectable nucleoside analogue developed by Gilead Sciences, that led to chain termination of viral RNA synthesis and showed broad antiviral activity against RNA viruses. Early clinical results were mixed: The US ACTT\u20101 trial reported an accelerated recovery and reduced mortality in treated patients, while the WHO Solidarity and a European trial revealed no impact of remdesivir on mortality. In contrast, a US trial in outpatients demonstrated a clear clinical benefit when treatment was administered early. Molnupiravir, an orally applicable nucleoside analogue developed by Merck, induces lethal mutations in the viral genome rather than chain termination. Molnupiravir showed in\u00a0vivo antiviral activity against coronaviruses in different animals. In MOVe\u2010OUT trials, molnupiravir reduced the rate of hospitalisation in treated outpatients. In the PANORAMIC trial, molnupiravir reduced the time to recovery in outpatients but not their rate of hospitalisation. No drug effect of molnupiravir was seen in the RECOVERY trial with hospitalised COVID\u201019 patients. Using structural biology and medicinal chemistry approaches, Pfizer developed nirmatrelvir, an oral inhibitor of the major coronavirus protease. In high\u2010risk but not in standard\u2010risk COVID\u201019 patients, the combination nirmatrelvir\/ritonavir reduced the rate of hospitalisation (EPIC HR and SR trials). Retrospective cohort studies showed treatment effects in defined patient groups. This review compares the efficacy and clinical performance of different antivirals, including emerging drugs such as obeldesivir and alternative protease inhibitors (lopinavir, simnotrelvir). It further examines their roles in prophylaxis, treatment of long covid symptoms, pharmacological considerations and antiviral resistance. Particular attention is given to factors underlying variable outcome of the trials, including viral variant evolution, population immunity increases, disease severity changes and timing of therapy initiation.<\/jats:p>","DOI":"10.1111\/1751-7915.70342","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T12:25:44Z","timestamp":1774959944000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Antivirals Targeting Coronavirus\n                    <scp>RNA<\/scp>\n                    \u2010Dependent\n                    <scp>RNA<\/scp>\n                    Polymerase and Main Protease: From Mechanisms of Action to Outcomes in\n                    <scp>COVID<\/scp>\n                    \u201019 Clinical Trials"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4783-8583","authenticated-orcid":false,"given":"Harald","family":"Br\u00fcssow","sequence":"first","affiliation":[{"name":"Department of Biosystems, Laboratory of Gene Technology KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473\u20103099(22)00295\u2010X"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473\u20103099(21)00485\u20100"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473\u20103099(23)00011\u20107"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00221\u201018"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01348\u201019"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473\u20103099(24)00436\u20105"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2204919"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2100044"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaf111"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2007764"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/1751\u20107915.13916"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/1751\u20107915.13889"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(22)02597\u20101"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2301425"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2001282"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2208822"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2100043"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2206449"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201064851\u20108"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.ads6028"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564\u2010020\u201000835\u20102"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad946"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1922083117"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.7326\/M22\u20102141"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abl7430"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2023.5099"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201029104\u2010y"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2024.2007"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2015301"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.013679"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2116846"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(24)01136\u2010X"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2007016"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD014962.pub2"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad409"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2309003"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2118542"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciae551"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2309002"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2024.106339"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473\u20103099(24)00431\u20106"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2022.100735"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01063"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj\u20102024\u2010081165"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010022\u201005514\u20102"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2116044"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201042102\u2010y"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiad275"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473\u20103099(22)00644\u20102"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41586\u2010023\u201003248\u20103"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41586\u2010022\u201002939\u20107"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473\u20103099(23)00118\u20104"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201032045\u20101"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aau9242"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13732"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c00750"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac933"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac781"},{"key":"e_1_2_13_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201033825\u20105"},{"key":"e_1_2_13_61_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp2304550"},{"key":"e_1_2_13_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473\u20103099(25)00238\u20105"},{"key":"e_1_2_13_63_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl4784"},{"key":"e_1_2_13_64_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02428\u201020"},{"key":"e_1_2_13_65_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adk3295"},{"key":"e_1_2_13_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473\u20103099(25)00093\u20103"},{"key":"e_1_2_13_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD015395.pub3"},{"key":"e_1_2_13_68_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe2407575"},{"key":"e_1_2_13_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006649\u20106"},{"key":"e_1_2_13_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473\u20103099(25)00073\u20108"},{"key":"e_1_2_13_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473\u20103099(23)00493\u20100"},{"key":"e_1_2_13_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473\u20103099(25)00482\u20107"},{"key":"e_1_2_13_73_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aal3653"},{"key":"e_1_2_13_74_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abb5883"},{"key":"e_1_2_13_75_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.16349"},{"key":"e_1_2_13_76_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaf406"},{"key":"e_1_2_13_77_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.1.244\u2010254.2003"},{"key":"e_1_2_13_78_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009929"},{"key":"e_1_2_13_79_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD015381.pub2"},{"key":"e_1_2_13_80_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aax5866"},{"key":"e_1_2_13_81_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01965\u201017"},{"key":"e_1_2_13_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473\u20103099(24)00217\u20102"},{"key":"e_1_2_13_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(20)31022\u20109"},{"key":"e_1_2_13_84_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17180"},{"key":"e_1_2_13_85_1","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2025.2469648"},{"key":"e_1_2_13_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473\u20103099(25)00221\u2010X"},{"key":"e_1_2_13_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(22)00519\u20100"},{"key":"e_1_2_13_88_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2023184"},{"key":"e_1_2_13_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102423\u20105"},{"key":"e_1_2_13_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(22)01586\u20100"},{"key":"e_1_2_13_91_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403596101"},{"key":"e_1_2_13_92_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2023.0743"},{"key":"e_1_2_13_93_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj\u20102022\u2010074572"},{"key":"e_1_2_13_94_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc1560"},{"key":"e_1_2_13_95_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adl4013"},{"key":"e_1_2_13_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473\u20103099(24)00171\u20103"}],"container-title":["Microbial Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/sfamjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1751-7915.70342","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/sfamjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1751-7915.70342","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/sfamjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1751-7915.70342","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T04:27:42Z","timestamp":1778905662000},"score":1,"resource":{"primary":{"URL":"https:\/\/sfamjournals.onlinelibrary.wiley.com\/doi\/10.1111\/1751-7915.70342"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,31]]},"references-count":95,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1111\/1751-7915.70342"],"URL":"https:\/\/doi.org\/10.1111\/1751-7915.70342","archive":["Portico"],"relation":{},"ISSN":["1751-7915","1751-7915"],"issn-type":[{"value":"1751-7915","type":"print"},{"value":"1751-7915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,31]]},"assertion":[{"value":"2026-03-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70342"}}