{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T20:41:45Z","timestamp":1791837705953,"version":"4.3.4"},"reference-count":46,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T00:00:00Z","timestamp":1643760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI127639"],"award-info":[{"award-number":["R21AI127639"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Onchocerciasis and lymphatic filariasis are neglected tropical diseases caused by infection with filarial worms. Annual or biannual mass drug administration with microfilaricidal drugs that kill the microfilarial stages of the parasites has helped reduce infection rates and thus prevent transmission of both infections. However, success depends on high population coverage that is maintained for the duration of the adult worm\u2019s lifespan. Given that these filarial worms can live up to 14 years in their human hosts, a macrofilaricidal drug would vastly accelerate elimination efforts. Here, we have evaluated the repurposed drug pyrvinium pamoate as well as newly synthesized analogs of pyrvinium for their efficacy against filarial worms in vitro and in vivo. We found that pyrvinium pamoate, tetrahydropyrvinium and one of the analogs were highly potent in inhibiting worms in in vitro whole-worm screening assays, and that all three compounds reduced female worm fecundity and inhibited embryogenesis in the Brugia pahangi-gerbil in vivo model of infection.<\/jats:p>","DOI":"10.3390\/ph15020189","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T05:42:33Z","timestamp":1643866953000},"page":"189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Pyrvinium Pamoate and Structural Analogs Are Early Macrofilaricide Leads"],"prefix":"10.3390","volume":"15","author":[{"given":"Emma L.","family":"Gunderson","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford","family":"Bryant","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina A.","family":"Bulman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Vogel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kee-Chong","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shabnam","family":"Jawahar","sequence":"additional","affiliation":[{"name":"Molecular Parasitology, New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Tricoche","sequence":"additional","affiliation":[{"name":"Molecular Parasitology, New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Voronin","sequence":"additional","affiliation":[{"name":"Molecular Parasitology, New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Corbo","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Wagner College, Staten Island, NY 10301, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene B.","family":"Ayiseh","sequence":"additional","affiliation":[{"name":"ANDI Centre of Excellence for Onchocerciasis Drug Research, Biotechnology Unit, Faculty of Science, University of Buea, Buea P.O. Box 63, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faustin P. T.","family":"Manfo","sequence":"additional","affiliation":[{"name":"ANDI Centre of Excellence for Onchocerciasis Drug Research, Biotechnology Unit, Faculty of Science, University of Buea, Buea P.O. Box 63, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glory E.","family":"Mbah","sequence":"additional","affiliation":[{"name":"ANDI Centre of Excellence for Onchocerciasis Drug Research, Biotechnology Unit, Faculty of Science, University of Buea, Buea P.O. Box 63, Cameroon"},{"name":"Higher Teacher Training College (HTTC), The University of Bamenda, Bamenda P.O. Box 39, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fidelis","family":"Cho-Ngwa","sequence":"additional","affiliation":[{"name":"ANDI Centre of Excellence for Onchocerciasis Drug Research, Biotechnology Unit, Faculty of Science, University of Buea, Buea P.O. Box 63, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Beerntsen","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, University of Missouri-Columbia, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam R.","family":"Renslo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2389-6113","authenticated-orcid":false,"given":"Sara","family":"Lustigman","sequence":"additional","affiliation":[{"name":"Molecular Parasitology, New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy A.","family":"Sakanari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,2]]},"reference":[{"key":"ref_1","unstructured":"GBD 2017 Disease and Injury Incidence and Prevalence Collaborators (2018). Global, Regional, and National Incidence, Prevalence, and Years Lived with Disability for 354 Diseases and Injuries for 195 Countries and Territories, 1990\u20132017: A Systematic Analysis for the Global Burden of Disease Study 2017. Lancet, 392, 1789\u20131858."},{"key":"ref_2","first-page":"164","article-title":"An Overview of Lymphatic Filariasis Lymphedema","volume":"50","author":"Rajasekaran","year":"2017","journal-title":"Lymphology"},{"key":"ref_3","unstructured":"WHO (2016). Global Programme to Eliminate Lymphatic Filariasis: Progress Report, 2015. Relev. Epidemiol. Hebd., 91, 441\u2013455."},{"key":"ref_4","unstructured":"Ryan, E.T., Hill, D.R., Solomon, T., Aronson, N.E., and Endy, T.P. (2020). 27\u2014Neglected Tropical Diseases: Public Health Control Programs and Mass Drug Administration. Hunter\u2019s Tropical Medicine and Emerging Infectious Diseases, Elsevier. [10th ed.]."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1023\/A:1026546719091","article-title":"Longevity and Ageing in Parasitic and Free-Living Nematodes","volume":"1","author":"Gems","year":"2000","journal-title":"Biogerontology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/S0140-6736(96)11094-1","article-title":"Serious Reactions after Mass Treatment of Onchocerciasis with Ivermectin in an Area Endemic for Loa loa Infection","volume":"350","author":"Gardon","year":"1997","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1186\/1475-2883-2-S1-S4","article-title":"Clinical Picture, Epidemiology and Outcome of Loa-Associated Serious Adverse Events Related to Mass Ivermectin Treatment of Onchocerciasis in Cameroon","volume":"2","author":"Boussinesq","year":"2003","journal-title":"Filaria J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1186\/1756-3305-7-363","article-title":"Multidimensional Complexities of Filariasis Control in an Era of Large-Scale Mass Drug Administration Programmes: A Can of Worms","volume":"7","author":"Molyneux","year":"2014","journal-title":"Parasite Vectors"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.12688\/gatesopenres.13065.1","article-title":"The Roadmap towards Elimination of Lymphatic Filariasis by 2030: Insights from Quantitative and Mathematical Modelling","volume":"3","author":"Davis","year":"2019","journal-title":"Gates Open Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.12688\/gatesopenres.13067.1","article-title":"The World Health Organization 2030 Goals for Onchocerciasis: Insights and Perspectives from Mathematical Modelling","volume":"3","author":"Walker","year":"2019","journal-title":"Gates Open Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Tyagi, R., Bulman, C.A., Cho-Ngwa, F., Fischer, C., Marcellino, C., Arkin, M.R., McKerrow, J.H., McNamara, C.W., Mahoney, M., and Tricoche, N. (2021). An Integrated Approach to Identify New Anti-Filarial Leads to Treat River Blindness, a Neglected Tropical Disease. Pathogens, 10.","DOI":"10.3390\/pathogens10010071"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1002\/cpt1976196802","article-title":"Absorption of Pyrvinium Pamoate","volume":"19","author":"Smith","year":"1976","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7150\/oncm.20563","article-title":"Repurposing of Anthelminthics as Anticancer Drugs","volume":"3","author":"Hamilton","year":"2017","journal-title":"Oncomedicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7233","DOI":"10.1073\/pnas.0807282106","article-title":"Non-Competitive Androgen Receptor Inhibition in vitro and In Vivo","volume":"106","author":"Jones","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","unstructured":"Diamond, M.I., Jones, J.O., and Renslo, A.R. (2013). Small-Molecule Inhibitors of the Androgen Receptor. (8,580,773 B2), U.S. Patent."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"349","DOI":"10.4269\/ajtmh.1959.8.349","article-title":"The Treatment of Pinworm Infections in Humans (Enterobiasis) with Pyrvinium Cloride and Pyrvinium Pamoate","volume":"8","author":"Beck","year":"1959","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1001\/jama.1964.03070060121016","article-title":"Treatment of Pinworm Infections with Reduced Single Dose of Pyrvinium Pamoate","volume":"189","author":"Beck","year":"1964","journal-title":"JAMA J. Am. Med. Assoc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1001\/jama.1965.03090100093040","article-title":"Strongyloidiasis Treated with Pyrvinium Pamoate","volume":"193","author":"Wang","year":"1965","journal-title":"J. Am. Med. Assoc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1002\/j.1552-4604.1965.tb00229.x","article-title":"The Therapy of Trichuriasis with a Combination of Thiabendazole and Pyrvinium Pamoate","volume":"5","author":"Zucas","year":"1965","journal-title":"J. New Drugs"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.1128\/AAC.00207-08","article-title":"Efficacy of Pyrvinium Pamoate against Cryptosporidium parvum Infection in vitro and in a Neonatal Mouse Model","volume":"52","author":"Downey","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1093\/jac\/dkp296","article-title":"in vitro Activity of Pyrvinium Pamoate against Entamoeba histolytica and Giardia intestinalis Using Radiolabelled Thymidine Incorporation and an SYBR Green I-Based Fluorescence Assay","volume":"64","author":"Downey","year":"2009","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"127037","DOI":"10.1016\/j.bmcl.2020.127037","article-title":"Synthesis and Efficacy of Pyrvinium-Inspired Analogs against Tuberculosis and Malaria Pathogens","volume":"30","author":"Gaikwad","year":"2020","journal-title":"Biooroganic. Med. Chem. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"576975","DOI":"10.3389\/fcimb.2020.576975","article-title":"In Vitro and In Vivo Study of Antifungal Effect of Pyrvinium Pamoate Alone and in Combination with Azoles Against Exophiala dermatitidis","volume":"10","author":"Sun","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.cell.2015.01.026","article-title":"Targeting the Adaptability of Heterogeneous Aneuploids","volume":"160","author":"Chen","year":"2015","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Jawahar, S., Tricoche, N., Bulman, C.A., Sakanari, J., and Lustigman, S. (2021). Drugs That Target Early Stages of Onchocerca volvulus: A Revisited Means to Facilitate the Elimination Goals for Onchocerciasis. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009064"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1056\/NEJMoa1705026","article-title":"Test-and-Not-Treat Strategy for Onchocerciasis in Loa loa-Endemic Areas","volume":"377","author":"Kamgno","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_27","unstructured":"(2021, December 18). Drugs for Neglected Diseases Initiative (DNDi). Available online: https:\/\/dndi.org\/research-development\/portfolio\/."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"778724","DOI":"10.3389\/fitd.2021.778724","article-title":"Advances in Preclinical Platforms of Loa loa for Filarial Neglected Tropical Disease Drug and Diagnostics Research","volume":"2","author":"Wanji","year":"2021","journal-title":"Front. Trop. Dis."},{"key":"ref_29","unstructured":"DNDi (2021, December 18). Target Product Profile for River Blindness. Available online: https:\/\/dndi.org\/diseases\/filaria-river-blindness\/target-product-profile\/."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1172\/JCI4768","article-title":"Tetracycline Therapy Targets Intracellular Bacteria in the Filarial Nematode Litomosoides sigmodontis and Results in Filarial Infertility","volume":"103","author":"Hoerauf","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s00430-002-0174-6","article-title":"Doxycycline as a Novel Strategy against Bancroftian Filariasis\u2014Depletion of Wolbachia Endosymbionts from Wuchereria bancrofti and Stop of Microfilaria Production","volume":"192","author":"Hoerauf","year":"2003","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/s41598-017-00322-5","article-title":"Short-Course, High-Dose Rifampicin Achieves Wolbachia Depletion Predictive of Curative Outcomes in Preclinical Models of Lymphatic Filariasis and Onchocerciasis","volume":"7","author":"Aljayyoussi","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1016\/S0140-6736(05)66591-9","article-title":"Macrofilaricidal Activity after Doxycycline Treatment of Wuchereria bancrofti: A Double-Blind, Randomised Placebo-Controlled Trial","volume":"365","author":"Taylor","year":"2005","journal-title":"Lancet"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1111\/j.1365-3156.2007.01949.x","article-title":"Macrofilaricidal Effect of 4 Weeks of Treatment with Doxycycline on Wuchereria bancrofti","volume":"12","author":"Debrah","year":"2007","journal-title":"Trop. Med. Int. Health"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s00430-007-0072-z","article-title":"Wolbachia Endobacteria Depletion by Doxycycline as Antifilarial Therapy Has Macrofilaricidal Activity in Onchocerciasis: A Randomized Placebo-Controlled Study","volume":"197","author":"Hoerauf","year":"2008","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s00436-008-1217-8","article-title":"Efficacy of 5-Week Doxycycline Treatment on Adult Onchocerca volvulus","volume":"104","author":"Hoerauf","year":"2009","journal-title":"Parasitol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1007\/s00436-008-1133-y","article-title":"Efficacy of 2- and 4-Week Rifampicin Treatment on the Wolbachia of Onchocerca volvulus","volume":"103","author":"Specht","year":"2008","journal-title":"Parasitol. Res."},{"key":"ref_38","first-page":"841","article-title":"Susceptibility of Wolbachia, an Endosymbiont of Brugia malayi Microfilariae, to Doxycycline Determined by Quantitative PCR Assay","volume":"43","author":"Sungpradit","year":"2012","journal-title":"Southeast. Asian J. Trop. Med. Public Health"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1093\/cid\/civ363","article-title":"Doxycycline Leads to Sterility and Enhanced Killing of Female Onchocerca volvulus Worms in an Area with Persistent Microfilaridermia After Repeated Ivermectin Treatment: A Randomized, Placebo-Controlled, Double-Blind Trial","volume":"61","author":"Debrah","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3389\/fonc.2012.00137","article-title":"Reprofiling a Classical Anthelmintic, Pyrvinium Pamoate, as an Anti-Cancer Drug Targeting Mitochondrial Respiration","volume":"2","author":"Ishii","year":"2012","journal-title":"Front. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Xu, W., Lacerda, L., Debeb, B.G., Atkinson, R.L., Solley, T.N., Li, L., Orton, D., McMurray, J.S., Hang, B.I., and Lee, E. (2013). The Antihelmintic Drug Pyrvinium Pamoate Targets Aggressive Breast Cancer. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071508"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1002\/jcp.26006","article-title":"The Novel Role of Pyrvinium in Cancer Therapy","volume":"233","author":"Abdollahi","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1080\/22221751.2020.1720527","article-title":"Identification of Pyrvinium Pamoate as an Anti-Tuberculosis Agent in vitro and In Vivo by SOSA Approach amongst Known Drugs","volume":"9","author":"Guan","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Bulman, C.A., Bidlow, C.M., Lustigman, S., Cho-Ngwa, F., Williams, D., Rascon, A.A., Tricoche, N., Samje, M., Bell, A., and Suzuki, B. (2015). Repurposing Auranofin as a Lead Candidate for Treatment of Lymphatic Filariasis and Onchocerciasis. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003534"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Voronin, D., Tricoche, N., Jawahar, S., Shlossman, M., Bulman, C.A., Fischer, C., Suderman, M.T., Sakanari, J.A., and Lustigman, S. (2019). Development of a Preliminary In Vitro Drug Screening Assay Based on a Newly Established Culturing System for Pre-Adult Fifth-Stage Onchocerca volvulus Worms. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007108"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Gunderson, E.L., Vogel, I., Chappell, L., Bulman, C.A., Lim, K.C., Luo, M., Whitman, J.D., Franklin, C., Choi, Y.-J., and Lefoulon, E. (2020). The Endosymbiont Wolbachia Rebounds Following Antibiotic Treatment. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008623"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/2\/189\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:13:13Z","timestamp":1760134393000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/2\/189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,2]]},"references-count":46,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ph15020189"],"URL":"https:\/\/doi.org\/10.3390\/ph15020189","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,2]]}}}