在這篇回顧裡,Dr. Martinez整理了可能用於武漢肺炎感染的治療藥物。

目前最具前景的藥物是remdesivir,為一種核苷酸類似物的前體藥物(經人體代謝轉化後才具藥理作用的化合物),原用於治療伊波拉病毒感染。Remedsivir在細胞培養中可抑制SARS及MERS病毒的複製,在非人類的動物模型中具有療效。此外,HIV-1蛋白酶抑制劑的組合物lopinavir/ritonavir及interferon beta (LPV/RTV-INFb)在SARS病人亦有療效,在動物試驗中亦可改善MERS感染的臨床症狀。在MERS感染的動物模型中,remdesivir的療效似乎較LPV/RTV-INFb為佳。免疫反應似乎也是SARS、MERS、及武漢肺炎患者高死亡率的原因之一,目前尚不清楚免疫反應藥物是否有效,僅針對冠狀病毒的療法可能無法復原這些高致病性的感染。

(財團法人國家衛生研究院 莊淑鈞博士摘要整理)

Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV–IFN-β) was shown to be effective in patients infected with SARS-CoV. LPV/RTV–IFN-β also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV–IFN-β against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections.

Author:Miguel Angel Martinez
原文連結: https://is.gd/V2fPI6