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Ivermectin reduces coronavirus infection in vivo: a mouse experimental model
bioRxiv - Pathology Pub Date : 2020-11-02 , DOI: 10.1101/2020.11.02.363242
AP Arévalo , R Pagotto , J Pórfido , H Daghero , M Segovia , K Yamasaki , B Varela , M Hill , JM Verdes , M Duhalde Vega , M Bollati-Fogolín , M Crispo

SARS-CoV2 is a single strand RNA virus member of the type 2 coronavirus family, responsible for causing COVID-19 disease in humans. The objective of this study was to test the ivermectin drug in a murine model of coronavirus infection using a type 2 family RNA coronavirus similar to SARS-CoV2, the mouse hepatitis virus (MHV). BALB/cJ female mice were infected with 6,000 PFU of MHV-A59 (Group Infected; n=20) and immediately treated with one single dose of 500 ug/kg of ivermectin (Group Infected + IVM; n=20), or were not infected and treated with PBS (Control group; n=16). Five days after infection/treatment, mice were euthanized to obtain different tissues to check general health status and infection levels. Overall results demonstrated that viral infection induces the typical MHV disease in infected animals, with livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while ivermectin administration showed a better health status with lower viral load (23,192 AU; p<0.05) and few livers with histopathological damage (p<0.05), not showing statistical differences with control mice (P=NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in treated mice compared to infected animals. In conclusion, ivermectin seems to be effective to diminish MHV viral load and disease in mice, being a useful model for further understanding new therapies against coronavirus diseases.

中文翻译:

伊维菌素可减少体内冠状病毒感染:小鼠实验模型

SARS-CoV2是2型冠状病毒家族的单链RNA病毒成员,负责引起人类COVID-19疾病。这项研究的目的是在小鼠冠状病毒感染模型中使用类似于SARS-CoV2小鼠肝炎病毒(MHV)的2型家族RNA冠状病毒测试伊维菌素药物。BALB / cJ雌性小鼠感染了6,000 PFU的MHV-A59(感染组; n = 20),并立即用一剂500 ug / kg的伊维菌素(感染组+ IVM; n = 20)进行单次治疗,感染并用PBS治疗(对照组; n = 16)。感染/治疗五天后,对小鼠实施安乐死以获得不同的组织,以检查总体健康状况和感染水平。总体结果表明,病毒感染会在受感染的动物中诱发典型的MHV疾病,肝脏表现出严重的肝细胞坏死,并伴有严重的淋巴细胞质炎性浸润,伴有较高的肝病毒载量(52,158 AU),而伊维菌素的给药显示出更好的健康状态,而病毒载量较低(23,192 AU; p <0.05),并且很少有组织病理学的肝脏损伤(p <0.05),与对照小鼠(P = NS)未显示统计学差异。此外,与感染动物相比,治疗小鼠的血清转氨酶水平(天冬氨酸转氨酶和丙氨酸转氨酶)显着降低。总之,伊维菌素似乎可以有效减少小鼠的MHV病毒载量和疾病,是进一步了解针对冠状病毒疾病的新疗法的有用模型。
更新日期:2020-11-03
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