Treatment With Lopinavir/Ritonavir or Interferon-β1b Improves Outcome of MERS-CoV Infection in a Nonhuman Primate Model of Common Marmoset
By J. Chan, Yanfeng Yao, M. Yeung, Wei Deng, L. Bao, L. Jia, Feng-di Li, C. Xiao, Hong Gao, Pin Yu and 6 more. Journal of Infectious Diseases, 2015
647 citations recorded by the source corpus.
Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe disease in human with an overall case-fatality rate of >35%. Effective antivirals are crucial for improving the clinical outcome of MERS. Although a number of repurposed drugs, convalescent-phase plasma, antiviral peptides, and neutralizing antibodies exhibit anti-MERS-CoV activity in vitro, most are not readily available or have not been evaluated in nonhuman primates. We assessed 3 repurposed drugs with potent in vitro anti-MERS-CoV activity (mycophenolate mofetil [MMF], lopinavir/ritonavir, and interferon-β1b) in common marmosets with severe disease resembling MERS in humans. The lopinavir/ritonavir-treated and interferon-β1b-treated animals had better outcome than the untreated animals, with improved clinical (mean clinical scores ↓50.9%–95.0% and ↓weight loss than the untreated animals), radiological (minimal pulmonary infiltrates), and pathological (mild bronchointerstitial pneumonia) findings, and lower mean viral loads in necropsied lung (↓0.59–1.06 log10 copies/glyceraldehyde 3-phosphate dehydrogenase [GAPDH]; P < .050) and extrapulmonary (↓0.11–1.29 log10 copies/GAPDH; P < .050 in kidney) tissues. In contrast, all MMF-treated animals developed severe and/or fatal disease with higher mean viral loads (↑0.15–0.54 log10 copies/GAPDH) than the untreated animals. The mortality rate at 36 hours postinoculation was 67% (untreated and MMF-treated) versus 0–33% (lopinavir/ritonavir-treated and interferon-β1b-treated). Lopinavir/ritonavir and interferon-β1b alone or in combination should be evaluated in clinical trials. MMF alone may worsen MERS and should not be used.
Subfields: Animal Science and Zoology, Infectious Diseases
View Paper: https://www.semanticscholar.org/paper/e305232d5d27febe713580b020ad5cfa9d47a4dc
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Citations in the corpus
- From SARS to MERS, Thrusting Coronaviruses into the Spotlight (2019, background): “Host protease inhibitors Effective in mouse models [138] In vitro inhibition [138] Viral protease inhibitors In vitro inhibition [139] In vitro inhibition [140] Monoclonal and polyclonal antibodies Effective in mouse, ferrets, golden Syrian hamster [124, 141, 142] and non-human primate models [143, ”
- SARS-CoV-2 Vaccines: Status Report (2020, background): “Effectiveness of the combination was limited in mice but appreciable in NHP models of MERS-CoV (Chan et al., 2015; Sheahan et al., 2020).”
- SARS and MERS: recent insights into emerging coronaviruses (2016, positive): “However, lopinavir and ritonavir improve the outcome in common marmosets when treatment is initiated 6 hours after infection with MERS-CoV 105 .”
- Therapeutic options for the 2019 novel coronavirus (2019-nCoV) (2020, background): “2019-nCoV; MERS-CoV, SARS-CoV; HCoV-229E; HIV, HPV 3CLpro Lopinavir Inhibits 3CLpro • Approved for HIV • Phase 3 for 2019-nCoV (NCT04252274, NCT04251871, NCT04255017, ChiCTR2000029539) • Phase 2/3 for MERS (NCT02845843) [11, 18-21]”
- Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses (2017, background): “Very few small molecules have been assessed in CoV animal models of viral pathogenesis, and some have even been shown to exacerbate disease (for example, ribavirin and mycophenolic acid) (31, 32).”
- Coronavirus Infections in Children Including COVID-19 (2020, background): “154, 161 However, as previously mentioned, these results are considered inconclusive because of potential selection bias.”
- A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version) (2020, neutral): “1 抗病毒药物 (1)目前尚无来自RCTs的证据支持特异的抗2019-nCoV治疗疑似或确诊病例的药物;(2)可考虑试用 α-干扰素雾化吸入(成人500万U/次,加入灭菌注射用水,2次/d)(弱推荐);可考虑洛匹那韦/利托那韦口 服,2粒/次,2次/d(弱推荐)。 证据级别较低的研究如回顾性队列研究、历史对照研究、病例报告或系列案例报道证实单用洛匹那韦/ 利托那韦或与抗病毒药物联合使用在治疗SARS和MERS感染时有一定优势,如降低了ARDS的发生率或死 亡率([26-29])。一篇最新发表的系统评价显示,洛匹那韦/利托那韦的抗冠状病毒效果主要显现于早期应用, 可降低患者病死率和减少糖皮质激素”
- Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19 (2022, background): “Lopinavir-ritonavir or interferon beta-1b has been shown to reduce viral load of MERS-CoV and improve lung pathology in a nonhuman primate model of common marmoset [42].”