A phase 2a clinical trial of molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus.
A phase 2a clinical trial of molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus.
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DOI：
10.1126/scitranslmed.abl7430
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发表时间：
2022-01-19
影响因子：
17.1
通讯作者：
中科院分区：
文献类型：
--
作者：
迫切需要一种有效的口服直接作用疗法来阻止严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的传播并防止进展为严重的 2019 冠状病毒病 (COVID-19)。在一项 2a 期双盲、安慰剂对照、随机、多中心临床试验中，我们评估了核苷类似物 molnupiravir 在 202 名未接种疫苗的受试者中的安全性、耐受性和抗病毒功效，这些受试者确诊为 SARS-CoV-2 感染且症状持续时间<7 天。参与者按 1:1 的比例随机分配接受莫努匹拉韦（200 毫克）或安慰剂，然后按 3:1 的比例随机接受莫努匹拉韦（400 或 800 毫克）或安慰剂，每天口服两次，持续 5 天。通过逆转录酶聚合酶链反应 (RT-PCR) 评估鼻咽拭子中 SARS-CoV-2 RNA 的抗病毒活性。通过用鼻咽拭子样本接种培养的 Vero 细胞来评估感染性病毒，并通过 RT-PCR 进行检测。与安慰剂组（中位 15 天）相比，800 mg molnupiravir 组（中位 14 天）的病毒 RNA 清除时间（主要终点）缩短（对数秩 P 值 = 0.013）。截至研究结束（4 周），接受 800 毫克 molnupiravir 的参与者中，92.5% 的患者实现了病毒 RNA 清除，而安慰剂接受者的这一比例为 80.3%。在治疗第 3 天，800 mg molnupiravir 组中 1.9% 的拭子中检测到传染性病毒（次要终点），而安慰剂组中这一比例为 16.7%（P = 0.016）。在治疗第 5 天，接受 400 或 800 mg molnupiravir 的任何参与者均未分离出传染性病毒，而安慰剂接受者的这一比例为 11.1%（P 分别为 0.034 和 0.027）。莫努匹拉韦在所有剂量下均具有良好的耐受性。与安慰剂相比，Molnupiravir（800 毫克剂量）可加速 COVID-19 患者的 SARS-CoV-2 RNA 清除。尽管已经有了安全有效的疫苗，但 SARS-CoV-2 仍在全球范围内传播，导致高发病率和死亡率。当前的治疗在全球范围内提供在后勤上具有挑战性，这增加了对安全有效的口服疗法的需求。在一项针对患有 COVID-19 的成人门诊患者的莫尔努匹拉韦药物的随机、对照、双盲、多剂量研究中，800 毫克剂量比安慰剂更快地减少病毒 RNA，并消除鼻咽拭子中的传染性病毒（Fischer 等）。莫努匹拉韦是安全且耐受性良好的。快速消灭传染性病毒对于预防 SARS-CoV-2 传播具有重要意义。
There is an urgent need for an effective, oral, direct-acting therapeutic to block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent progression to severe coronavirus disease 2019 (COVID-19). In a phase 2a double-blind, placebo-controlled, randomized, multicenter clinical trial, we evaluated the safety, tolerability, and antiviral efficacy of the nucleoside analog molnupiravir in 202 unvaccinated participants with confirmed SARS-CoV-2 infection and symptom duration <7 days. Participants were randomized 1:1 to receive molnupiravir (200 mg) or placebo and then 3:1 to receive molnupiravir (400 or 800 mg) or placebo, orally twice daily for 5 days. Antiviral activity was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 RNA in nasopharyngeal swabs. Infectious virus was assessed by inoculation of cultured Vero cells with samples from nasopharyngeal swabs and was detected by RT-PCR. Time to viral RNA clearance (primary endpoint) was decreased in the 800-mg molnupiravir group (median 14 days) compared to the placebo group (median 15 days) (log rank P value = 0.013). Of participants receiving 800 mg of molnupiravir, 92.5% achieved viral RNA clearance compared with 80.3% of placebo recipients by study end (4 weeks). Infectious virus (secondary endpoint) was detected in swabs from 1.9% of the 800-mg molnupiravir group compared with 16.7% of the placebo group at day 3 of treatment (P = 0.016). At day 5 of treatment, infectious virus was not isolated from any participants receiving 400 or 800 mg of molnupiravir compared with 11.1% of placebo recipients (P = 0.034 and 0.027, respectively). Molnupiravir was well tolerated across all doses. Molnupiravir (800-mg dose) accelerated SARS-CoV-2 RNA clearance in patients with COVID-19 compared to placebo. Despite the availability of safe and effective vaccines, SARS-CoV-2 continues to spread globally, contributing to high morbidity and mortality. Current treatments are logistically challenging to provide on a global scale, increasing the need for safe and effective oral therapies. In a randomized, controlled, double-blind, multidose study of the drug molnupiravir in adult outpatients with COVID-19, an 800-mg dose reduced viral RNA more rapidly than placebo and eliminated infectious virus in nasopharyngeal swabs (Fischer et al.). Molnupiravir was safe and well tolerated. The rapid elimination of infectious virus has important implications for the prevention of SARS-CoV-2 transmission.
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影响因子：
19
作者：
Singanayagam, Anika;Patel, Monika;Gopal, Robin
通讯作者：
Gopal, Robin
DOI：
10.1056/nejmoa2029849
发表时间：
2021-01-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Chen P;Nirula A;Heller B;Gottlieb RL;Boscia J;Morris J;Huhn G;Cardona J;Mocherla B;Stosor V;Shawa I;Adams AC;Van Naarden J;Custer KL;Shen L;Durante M;Oakley G;Schade AE;Sabo J;Patel DR;Klekotka P;Skovronsky DM;BLAZE-1 Investigators
通讯作者：
BLAZE-1 Investigators
DOI：
10.1016/j.cmi.2021.02.014
发表时间：
2021-06
期刊：
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
影响因子：
--
作者：
Folgueira MD;Luczkowiak J;Lasala F;Pérez-Rivilla A;Delgado R
通讯作者：
Delgado R
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：
11.8
作者：
Bullard, Jared;Dust, Kerry;Poliquin, Guillaume
通讯作者：
Poliquin, Guillaume