Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets.
Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets.
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DOI：
10.1038/s41564-020-00835-2
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发表时间：
2021-01
影响因子：
28.3
通讯作者：
Plemper RK
中科院分区：
文献类型：
--
作者：
Cox RM;Wolf JD;Plemper RK
2019冠状病毒病（COVID-19）大流行对人类健康造成灾难性影响1。广泛的社区传播引发了严格的隔离措施，造成了严重的社会经济后果。控制大流行将取决于阻断传播链，直到疫苗诱导或自然获得的保护性群体免疫出现。然而，批准的抗病毒治疗，如瑞德西韦和恢复血清不能口服2，3，使他们不适合传播控制。我们先前报道了一种口服有效的流感病毒核糖核苷类似物抑制剂MK-4482/EIDD-2801的开发（参考文献10）。4，5），该药物被重新用于对抗严重急性呼吸综合征冠状病毒2（SARS-CoV-2），目前正在进行II/III期临床试验（NCT 04405570和NCT 04405739）。在这里，我们探索了MK-4482/EIDD-2801治疗性给药在雪貂模型中减轻SARS-CoV-2感染和阻断传播的有效性，因为雪貂和黄鼠狼属的相关成员有效地传播病毒，临床症状最小6，7，8，9，这类似于在人类成年人群中的传播。我们证明了鼻组织和分泌物中SARS-CoV-2的高负荷，这与通过直接接触的有效传播相吻合。每天两次用MK-4482/EIDD-2801治疗感染动物，显著降低了上呼吸道中的SARS-CoV-2负荷，并完全抑制了向未治疗接触动物的传播。这项研究确定了口服MK-4482/EIDD-2801作为一种有前途的抗病毒对策，以打破SARS-CoV-2社区传播链。
The coronavirus disease 2019 (COVID-19) pandemic is having a catastrophic impact on human health 1. Widespread community transmission has triggered stringent distancing measures with severe socio-economic consequences. Gaining control of the pandemic will depend on the interruption of transmission chains until vaccine-induced or naturally acquired protective herd immunity arises. However, approved antiviral treatments such as remdesivir and reconvalescent serum cannot be delivered orally 2, 3, making them poorly suitable for transmission control. We previously reported the development of an orally efficacious ribonucleoside analogue inhibitor of influenza viruses, MK-4482/EIDD-2801 (refs. 4, 5), that was repurposed for use against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is currently in phase II/III clinical trials (NCT04405570 and NCT04405739). Here, we explored the efficacy of therapeutically administered MK-4482/EIDD-2801 to mitigate SARS-CoV-2 infection and block transmission in the ferret model, given that ferrets and related members of the weasel genus transmit the virus efficiently with minimal clinical signs 6, 7, 8, 9, which resembles the spread in the human young-adult population. We demonstrate high SARS-CoV-2 burden in nasal tissues and secretions, which coincided with efficient transmission through direct contact. Therapeutic treatment of infected animals with MK-4482/EIDD-2801 twice a day significantly reduced the SARS-CoV-2 load in the upper respiratory tract and completely suppressed spread to untreated contact animals. This study identified oral MK-4482/EIDD-2801 as a promising antiviral countermeasure to break SARS-CoV-2 community transmission chains.
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影响因子：
7.4
作者：
Salajegheh Tazerji S;Magalhães Duarte P;Rahimi P;Shahabinejad F;Dhakal S;Singh Malik Y;Shehata AA;Lama J;Klein J;Safdar M;Rahman MT;Filipiak KJ;Rodríguez-Morales AJ;Sobur MA;Kabir F;Vazir B;Mboera L;Caporale M;Islam MS;Amuasi JH;Gharieb R;Roncada P;Musaad S;Tilocca B;Koohi MK;Taghipour A;Sait A;Subbaram K;Jahandideh A;Mortazavi P;Abedini MA;Hokey DA;Hogan U;Shaheen MNF;Elaswad A;Elhaig MM;Fawzy M
通讯作者：
Fawzy M
SARS-COV-2在人类和貂皮之间的貂皮农场上传播，然后回到人类。
DOI：
10.1126/science.abe5901
发表时间：
2021-01-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Oude Munnink BB;Sikkema RS;Nieuwenhuijse DF;Molenaar RJ;Munger E;Molenkamp R;van der Spek A;Tolsma P;Rietveld A;Brouwer M;Bouwmeester-Vincken N;Harders F;Hakze-van der Honing R;Wegdam-Blans MCA;Bouwstra RJ;GeurtsvanKessel C;van der Eijk AA;Velkers FC;Smit LAM;Stegeman A;van der Poel WHM;Koopmans MPG
通讯作者：
Koopmans MPG
DOI：
10.1016/j.trsl.2019.12.002
发表时间：
2020-04
期刊：
Translational research : the journal of laboratory and clinical medicine
影响因子：
--
作者：
Toots M;Yoon JJ;Hart M;Natchus MG;Painter GR;Plemper RK
通讯作者：
Plemper RK
影响因子：
7.6
作者：
Painter, George R.;Bowen, Richard A.;Kolykhalov, Alexander A.
通讯作者：
Kolykhalov, Alexander A.
影响因子：
4.9
作者：
Yoon, Jeong-Joong;Toots, Mart;Plemper, Richard K.
通讯作者：
Plemper, Richard K.