Systems and Clinical Pharmacology of COVID-19 Therapeutic Candidates: A Clinical and Translational Medicine Perspective.
Systems and Clinical Pharmacology of COVID-19 Therapeutic Candidates: A Clinical and Translational Medicine Perspective.
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新冠病毒治疗候选药物的系统与临床药理学：临床与转化医学视角
DOI：
10.1016/j.xphs.2020.11.019
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发表时间：
2021-03
影响因子：
3.8
通讯作者：
Ho RJY
中科院分区：
文献类型：
--
作者：
Perazzolo S;Zhu L;Lin W;Nguyen A;Ho RJY
超过5000万人感染了SARS-CoV-2病毒，约100万人因COVID-19疾病进展而死亡。COVID-19表现出类似流感的症状，可在发病后约7-10天内升级为细胞因子风暴，导致呼吸衰竭和死亡。虽然保持社会距离可以减少传播，但COVID-19疫苗和治疗方法对于恢复社会经济正常至关重要。即使发现了有效和安全的疫苗，仍然需要药物干预来限制疾病的严重程度和死亡率。整合目前的知识和正在进行临床研究的候选药物（在ClinicalTrials.gov注册的>3000候选药物中批准重新定位的药物），我们采用系统药理学方法来预测如何对抗病毒药物和免疫调节剂的使用进行最佳评估。抗病毒药物可能仅在感染早期、暴露后不久和住院前有效，而免疫调节剂应在后期细胞因子风暴中有效。由于目前的抗病毒候选药物需要在医院进行5-7天的治疗，因此针对SARS-CoV-2生命周期多个步骤的长效组合可能会在门诊环境中提供持久的单剂量治疗。即使有了疫苗，也可能仍然需要长效疗法，因为疫苗很可能是根据50%的效力目标批准的。
Over 50 million people have been infected with the SARS-CoV-2 virus, while around 1 million have died due to COVID-19 disease progression. COVID-19 presents flu-like symptoms that can escalate, in about 7–10 days from onset, into a cytokine storm causing respiratory failure and death. Although social distancing reduces transmissibility, COVID-19 vaccines and therapeutics are essential to regain socioeconomic normalcy. Even if effective and safe vaccines are found, pharmacological interventions are still needed to limit disease severity and mortality. Integrating current knowledge and drug candidates (approved drugs for repositioning among >35 candidates) undergoing clinical studies (>3000 registered in ClinicalTrials.gov), we employed Systems Pharmacology approaches to project how antivirals and immunoregulatory agents could be optimally evaluated for use. Antivirals are likely to be effective only at the early stage of infection, soon after exposure and before hospitalization, while immunomodulatory agents should be effective in the later-stage cytokine storm. As current antiviral candidates are administered in hospitals over 5–7 days, a long-acting combination that targets multiple SARS-CoV-2 lifecycle steps may provide a long-lasting, single-dose treatment in outpatient settings. Long-acting therapeutics may still be needed even when vaccines become available as vaccines are likely to be approved based on a 50% efficacy target.
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