{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:55:47Z","timestamp":1793159747305,"version":"4.5.0"},"reference-count":51,"publisher":"National Academy of Sciences","issue":"38","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"LIFE-GREENAPI","award":["101114152"],"award-info":[{"award-number":["101114152"]}]},{"name":"National innovation and Enterpreneurship training program for undergraduate","award":["345"],"award-info":[{"award-number":["345"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,9,23]]},"abstract":"<jats:p>\n                    This study presents a comparative cradle-to-gate environmental and economic evaluation of nine synthetic routes for Molnupiravir (EIDD-2801), a broad-spectrum antiviral drug. Integrating Life Cycle Assessment (LCA) with Life Cycle Costing (LCC), we quantified the environmental impacts alongside capital and operational costs, net present costs, and break-even prices of each route. The results reveal significant variation across the schemes, with\n                    <jats:italic toggle=\"yes\">Schemes #1<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">#2<\/jats:italic>\n                    exhibiting the highest impacts and costs due to intensive use of chloroform and diethyl ether, while\n                    <jats:italic toggle=\"yes\">Scheme #8<\/jats:italic>\n                    demonstrated the lowest impacts and costs, benefitting from higher batch output, greener solvents, and process intensification. Scenario analyses showed that solvent recovery improves sustainability only when high recovery rates are combined with clean electricity; otherwise, the additional energy demand may offset benefits. Scale-up analysis confirmed that higher production scales substantially reduce per-gram impacts and costs, supporting economies of scale. These findings highlight the critical role of solvent management, energy sourcing, the use of sustainability assessment at the earliest stages of innovation, and process design in aligning green chemistry with economic viability. The proposed integrated LCA-LCC framework provides transferable insights to guide sustainable pharmaceutical manufacturing and supports the development of evidence-based policy for greener antiviral drug production.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2502336122","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T17:53:16Z","timestamp":1758217996000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Divergent sustainability profiles of molnupiravir synthesis routes are governed by solvent use and process design"],"prefix":"10.1073","volume":"122","author":[{"given":"Zhengyun","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Engineering, China Pharmaceutical University","place":["Nanjing, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0254-4516","authenticated-orcid":false,"given":"Justin Z.","family":"Lian","sequence":"additional","affiliation":[{"name":"Department of Industrial Ecology, Institute of Environmental Science\u2013Industrial Ecology, Leiden University","place":["Leiden, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haozhou","family":"Huang","sequence":"additional","affiliation":[{"name":"Courant Institute of Mathematical Sciences, New York University","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengyi","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Pharmacy, China Pharmaceutical University","place":["Nanjing, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda Thubelihle","family":"Kanye","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, China Pharmaceutical University","place":["Nanjing, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateng","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, China Pharmaceutical University","place":["Nanjing, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihao","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, China Pharmaceutical University","place":["Nanjing, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boxin","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, China Pharmaceutical University","place":["Nanjing, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3534-9299","authenticated-orcid":false,"given":"Jiawei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Aeronautics, Imperial College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajaz","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of California","place":["Los Angeles"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0519-6968","authenticated-orcid":false,"given":"Valerio","family":"Barbarossa","sequence":"additional","affiliation":[{"name":"Department of Industrial Ecology, Institute of Environmental Science\u2013Industrial Ecology, Leiden University","place":["Leiden, The Netherlands"]},{"name":"PBL Netherlands Environmental Assessment Agency","place":["The Hague, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Cucurachi","sequence":"additional","affiliation":[{"name":"Department of Industrial Ecology, Institute of Environmental Science\u2013Industrial Ecology, Leiden University","place":["Leiden, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, China Pharmaceutical University","place":["Nanjing, People\u2019s Republic of China"]},{"name":"Engineering Research Center for Smart Pharmaceutical Manufacturing Technologies, Ministry of Education, China Pharmaceutical University","place":["Nanjing, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms12030600"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00766-18"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1039\/D0CC05944G"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.1585"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2016.81"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.20225"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2019.12.002"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00291-21"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13395"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-021-05538-5"},{"key":"e_1_3_4_11_2","unstructured":"Merck and Ridgeback Biotherapeutics Merck and Ridgeback\u2019s Molnupiravir an oral COVID-19 antiviral medicine receives first authorization in the world. Merck & Co. Inc. news release; November 4 2021. https:\/\/www.merck.com\/news\/merck-and-ridgebacks-molnupiravir-an-oral-covid-19-antiviral-medicine-receives-first-authorization-in-the-world\/. Accessed 15 November 2024."},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1039\/D2RA05064A"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1055\/a-1275-2848"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.1c04550"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coche.2019.01.003"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/acssuschemeng.9b00480"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11367-020-01856-z"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coche.2019.09.009"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/acssuschemeng.8b05473"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2020.05.001"},{"key":"e_1_3_4_21_2","unstructured":"ecoinvent Association ecoinvent database. Technoparkstrasse 1 Zurich Switzerland. https:\/\/www.ecoinvent.org. Accessed 12 September 2024."},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11367-010-0151-z"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/acssuschemeng.2c06681"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.7b00923"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11367-020-01857-y"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11367-022-02064-7"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15162-7"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1139(03)00105-2"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.3390\/su14063161"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jobe.2018.03.015"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/acssuschemeng.0c02211"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.oprd.8b00237"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclepro.2020.121204"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1039\/c003666h"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10098-017-1444-8"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclepro.2024.142550"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11367-016-1228-0"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.simpa.2019.100012"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclepro.2017.08.109"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joule.2024.09.007"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.3390\/su11010208"},{"key":"e_1_3_4_42_2","first-page":"859","article-title":"Policy innovation of life cycle management of industrial land supply in China","volume":"11","author":"Luo Y.","year":"2022","unstructured":"Y. Luo, C. Li, J. Zhi, Q. Wu, J. Yao, Policy innovation of life cycle management of industrial land supply in China. Land (Basel) 11, 859 (2022).","journal-title":"Land (Basel)"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-29928-8"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/open.201900015"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclepro.2016.06.164"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.oprd.6b00275"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2323"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/bbb.1949"},{"key":"e_1_3_4_49_2","doi-asserted-by":"crossref","unstructured":"A. Shah C. R. C. Mat A. Ibrahim Y. Zhang S. Muzammil \u201cCurrent practices in industrial ecology\u201d in Industrial Ecology (Springer Singapore 2024) pp. 21\u201334.","DOI":"10.1007\/978-981-97-3619-5_2"},{"key":"e_1_3_4_50_2","unstructured":"ISO 14040 \u201cEnvironmental management-life cycle assessment-principles and framework\u201d (International Organization for Standardization Geneva Switzerland 2006)."},{"key":"e_1_3_4_51_2","unstructured":"A. Damodaran Cost of capital by sector. NYU Stern School of Business. https:\/\/pages.stern.nyu.edu\/~adamodar\/New_Home_Page\/datafile\/wacc.htm. Accessed 1 January 2025."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2502336122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T17:53:57Z","timestamp":1758218037000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2502336122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,18]]},"references-count":51,"journal-issue":{"issue":"38","published-print":{"date-parts":[[2025,9,23]]}},"alternative-id":["10.1073\/pnas.2502336122"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2502336122","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,18]]},"assertion":[{"value":"2025-01-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2502336122"}}