Comparing molnupiravir and nirmatrelvir/ritonavir efficacy and the effects on SARS-CoV-2 transmission in animal models.
Comparing molnupiravir and nirmatrelvir/ritonavir efficacy and the effects on SARS-CoV-2 transmission in animal models.
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DOI：
10.1038/s41467-023-40556-8
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发表时间：
2023-08-07
影响因子：
16.6
通讯作者：
Plemper, Richard K.
中科院分区：
文献类型：
--
作者：
Cox, Robert M.;Lieber, Carolin M.;Wolf, Josef D.;Karimi, Amirhossein;Lieberman, Nicole A. P.;Sticher, Zachary M.;Roychoudhury, Pavitra;Andrews, Meghan K.;Krueger, Rebecca E.;Natchus, Michael G.;Painter, George R.;Kolykhalov, Alexander A.;Greninger, Alexander L.;Plemper, Richard K.
针对SARS-CoV-2的治疗选择未得到充分利用。两种口服药物，莫努匹拉韦和帕昔洛韦（nirmatrelvir/ritonavir），已获得紧急使用许可。最初的试验表明，paxlovid的疗效更好，但最近的研究表明，在老年人中的效力相当。在这里，我们在两种动物模型中比较了这两种药物; Roborovski侏儒仓鼠严重COVID-19样肺部感染模型和雪貂SARS-CoV-2传播模型。用任一种药物治疗的侏儒仓鼠在VOC微粒子感染后存活，肺滴度降低相当。每日两次接受1.25 mg/kg莫努匹韦的雌性雪貂的上呼吸道中的病毒RNA拷贝没有显著降低，但感染滴度降低了>2个对数级，并且停止了直接接触传播。每日两次给予20或100 mg/kg Nirmatrelvir/利托那韦的雌性雪貂显示病毒RNA拷贝和感染滴度降低1-2个对数级，这与鼻甲中的低Nirmatrelvir暴露相关。病毒复制在Nirmatrelvir/利托那韦治疗结束时重新出现，病毒有效传播（20 mg/kg组）或部分传播（100 mg/kg组）。用20 mg/kg的Nirmatrelvir/利托那韦进行预防性治疗不能防止感染雪貂的传播，但预防性5 mg/kg的Molnupiravir或100 mg/kg的Nirmatrelvir/利托那韦阻断了生产性传播。这些数据证实了在老年人中类似疗效的报道，并提供了抗病毒治疗可能的流行病学益处。关于SARS-CoV-2抗病毒药物在疗效和阻断传播方面的比较数据有限。在这里，作者用莫努匹拉韦或帕昔洛韦治疗侏儒仓鼠和雪貂，发现对严重的COVID-19样疾病的疗效相当，并完全阻断了莫努匹拉韦的传播。
Therapeutic options against SARS-CoV-2 are underutilized. Two oral drugs, molnupiravir and paxlovid (nirmatrelvir/ritonavir), have received emergency use authorization. Initial trials suggested greater efficacy of paxlovid, but recent studies indicated comparable potency in older adults. Here, we compare both drugs in two animal models; the Roborovski dwarf hamster model for severe COVID-19-like lung infection and the ferret SARS-CoV-2 transmission model. Dwarf hamsters treated with either drug survive VOC omicron infection with equivalent lung titer reduction. Viral RNA copies in the upper respiratory tract of female ferrets receiving 1.25 mg/kg molnupiravir twice-daily are not significantly reduced, but infectious titers are lowered by >2 log orders and direct-contact transmission is stopped. Female ferrets dosed with 20 or 100 mg/kg nirmatrelvir/ritonavir twice-daily show 1–2 log order reduction of viral RNA copies and infectious titers, which correlates with low nirmatrelvir exposure in nasal turbinates. Virus replication resurges towards nirmatrelvir/ritonavir treatment end and virus transmits efficiently (20 mg/kg group) or partially (100 mg/kg group). Prophylactic treatment with 20 mg/kg nirmatrelvir/ritonavir does not prevent spread from infected ferrets, but prophylactic 5 mg/kg molnupiravir or 100 mg/kg nirmatrelvir/ritonavir block productive transmission. These data confirm reports of similar efficacy in older adults and inform on possible epidemiologic benefit of antiviral treatment. There is limited data on how SARS-CoV-2 antivirals compare regarding efficacy and blocking transmission. Here, treating dwarf hamsters and ferrets with either molnupiravir or paxlovid the authors find comparable efficacy against severe COVID-19-like disease and complete block of transmission by molnupiravir.
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影响因子：
17.1
作者：
通讯作者：
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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：
10.1056/nejmoa2118542
发表时间：
2022-04-14
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hammond J;Leister-Tebbe H;Gardner A;Abreu P;Bao W;Wisemandle W;Baniecki M;Hendrick VM;Damle B;Simón-Campos A;Pypstra R;Rusnak JM;EPIC-HR Investigators
通讯作者：
EPIC-HR Investigators
DOI：
10.1016/s0140-6736(22)02597-1
发表时间：
2023-01-28
期刊：
Lancet (London, England)
影响因子：
--
作者：
通讯作者：
--
影响因子：
30.3
作者：
Kim, Young-Il;Kim, Seong-Gyu;Choi, Young Ki
通讯作者：
Choi, Young Ki