دورية أكاديمية
The new generation hdhodh inhibitor meds433 hinders the in vitro replication of sars-cov-2 and other human coronaviruses
| العنوان: | The new generation hdhodh inhibitor meds433 hinders the in vitro replication of sars-cov-2 and other human coronaviruses |
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| المؤلفون: | Calistri, Arianna, Montserrat Pulido, Núria, Mirazimi, Ali, Lolli, Marco Lucio, Parolin, Cristina, Luganini, Anna, Mognetti, Barbara, Elder, Elizabeth, Sibille, Giulia, Conciatori, Valeria, Vecchio, Claudia del, Sainas, Stefano, Boschi, Donatella |
| المصدر: | Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC)) |
| بيانات النشر: | MDPI AG |
| سنة النشر: | 2021 |
| المجموعة: | Dipòsit Digital de la Universitat de Barcelona |
| مصطلحات موضوعية: | Betacoronavirus, Antiretrovirals, Antiretroviral agents |
| الوصف: | Although coronaviruses (CoVs) have long been predicted to cause zoonotic diseases and pandemics with high probability, the lack of effective anti-pan-CoVs drugs rapidly usable against the emerging SARS-CoV-2 actually prevented a promptly therapeutic intervention for COVID-19. Development of host-targeting antivirals could be an alternative strategy for the control of emerging CoVs infections, as they could be quickly repositioned from one pandemic event to another. To contribute to these pandemic preparedness efforts, here we report on the broad-spectrum CoVs antiviral activity of MEDS433, a new inhibitor of the human dihydroorotate dehydrogenase (hDHODH), a key cellular enzyme of the de novo pyrimidine biosynthesis pathway. MEDS433 in-hibited the in vitro replication of hCoV-OC43 and hCoV-229E, as well as of SARS-CoV-2, at low nanomolar range. Notably, the anti-SARS-CoV-2 activity of MEDS433 against SARS-CoV-2 was also observed in kidney organoids generated from human embryonic stem cells. Then, the antiviral activity of MEDS433 was reversed by the addition of exogenous uridine or the product of hDHODH, the orotate, thus confirming hDHODH as the specific target of MEDS433 in hCoVs-infected cells. Taken together, these findings suggest MEDS433 as a potential candidate to develop novel drugs for COVID-19, as well as broad-spectrum antiviral agents exploitable for future CoVs threats. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 16 p.; application/pdf |
| اللغة: | English |
| تدمد: | 2076-2607 |
| العلاقة: | Reproducció del document publicat a: https://doi.org/10.3390/microorganisms9081731Test; Microorganisms, 2021, vol 9, num 8; https://doi.org/10.3390/microorganisms9081731Test; info:eu-repo/grantAgreement/EC/H2020/871029/EU//EVA-GLOBAL; http://hdl.handle.net/2445/184453Test; 6524904 |
| الإتاحة: | https://doi.org/10.3390/microorganisms9081731Test http://hdl.handle.net/2445/184453Test |
| حقوق: | cc by (c) Calistri, Arianna et al, 2021 ; http://creativecommons.org/licenses/by/3.0/esTest/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.A2360572 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20762607 |
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