دورية أكاديمية
Evaluation of anticoagulant agents for the treatment of human metapneumovirus infection in mice.
| العنوان: | Evaluation of anticoagulant agents for the treatment of human metapneumovirus infection in mice. |
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| المؤلفون: | Lê BV; 1Infectious Disease Research Centre, Laval University, Quebec City, Quebec, Canada., Jandrot-Perrus M; 2INSERM UMR_S1148, Paris Diderot University, Paris, France., Couture C; 3Quebec Heart and Lung Institute, Laval University, Quebec City, Quebec, Canada., Checkmahomed L; 1Infectious Disease Research Centre, Laval University, Quebec City, Quebec, Canada., Venable MC; 1Infectious Disease Research Centre, Laval University, Quebec City, Quebec, Canada., Hamelin MÈ; 1Infectious Disease Research Centre, Laval University, Quebec City, Quebec, Canada., Boivin G; 1Infectious Disease Research Centre, Laval University, Quebec City, Quebec, Canada. |
| المصدر: | The Journal of general virology [J Gen Virol] 2018 Oct; Vol. 99 (10), pp. 1367-1380. Date of Electronic Publication: 2018 Aug 10. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Microbiology Society Country of Publication: England NLM ID: 0077340 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1465-2099 (Electronic) Linking ISSN: 00221317 NLM ISO Abbreviation: J Gen Virol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2015- : London : Microbiology Society Original Publication: London, Cambridge Univ. Press for the Society for General Microbiology. |
| مواضيع طبية MeSH: | Anticoagulants/*administration & dosage , Heparin/*administration & dosage , Paramyxoviridae Infections/*drug therapy , Warfarin/*administration & dosage, Animals ; Arginine/analogs & derivatives ; Disease Models, Animal ; Metapneumovirus/drug effects ; Metapneumovirus/isolation & purification ; Mice ; Paramyxoviridae Infections/pathology ; Paramyxoviridae Infections/virology ; Pipecolic Acids/administration & dosage ; Sulfonamides ; Survival Analysis ; Treatment Outcome ; Viral Load ; Virus Replication/drug effects |
| مستخلص: | Thrombin has been demonstrated to be involved in several viral diseases including human metapneumovirus (hMPV) infections. We previously showed that immediate administration of thrombin inhibitor argatroban post-infection protected mice against hMPV disease. This current work aims at determining whether warfarin and heparin, two other anticoagulants inhibiting thrombin formation and activities, may also be used for treatment against hMPV in vivo. We found that immediate injections of argatroban, warfarin or heparin after virus challenge protected mice against hMPV infection, as evidenced by decreased or no mortality, less weight loss, reduced viral load and attenuated inflammation. However, delayed treatments starting 1 day post-infection with argatroban or warfarin almost did not impact the survival whereas delayed treatment with heparin induced an increased mortality during infection. Moreover, these treatments also did not reduce weight loss, viral replication and inflammation. In agreement with these results, thrombin generation was decreased upon immediate anticoagulant treatments but was unaltered upon delayed treatments. Thus, thrombin generation occurs at the onset of hMPV infection and thrombin inhibition may be only useful for the treatment of this disease when initiated in the early stage. In this case, heparin is not recommended because of its reduced efficacy on mortality in infected mice whereas argatroban and warfarin appear as safe and effective drugs for the treatment of hMPV disease. The antiviral and anti-inflammatory effects of argatroban occur via thrombin-dependent pathways whereas the mechanisms by which warfarin exerts its beneficial effects against hMPV infection were not elucidated and need to be further studied. |
| معلومات مُعتمدة: | 273261 Canada CIHR |
| فهرسة مساهمة: | Keywords: PAR1; argatroban; hMPV; heparin; thrombin; warfarin |
| المشرفين على المادة: | 0 (Anticoagulants) 0 (Pipecolic Acids) 0 (Sulfonamides) 5Q7ZVV76EI (Warfarin) 9005-49-6 (Heparin) 94ZLA3W45F (Arginine) IY90U61Z3S (argatroban) |
| تواريخ الأحداث: | Date Created: 20180814 Date Completed: 20190904 Latest Revision: 20201209 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1099/jgv.0.001135 |
| PMID: | 30102144 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1465-2099 |
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| DOI: | 10.1099/jgv.0.001135 |