The Texas A&M Drug Discovery Laboratory, Department of Chemistry, Texas A&M University, College Station, TX, 77843, USA.
Chembiochem. 2020 Mar 2;21(5):730-738. doi: 10.1002/cbic.202000047. Epub 2020 Feb 25.
With the current trajectory of the 2019-nCoV outbreak unknown, public health and medicinal measures will both be needed to contain spreading of the virus and to optimize patient outcomes. Although little is known about the virus, an examination of the genome sequence shows strong homology with its better-studied cousin, SARS-CoV. The spike protein used for host cell infection shows key nonsynonymous mutations that might hamper the efficacy of previously developed therapeutics but remains a viable target for the development of biologics and macrocyclic peptides. Other key drug targets, including RNA-dependent RNA polymerase and coronavirus main proteinase (3CLpro), share a strikingly high (>95 %) homology to SARS-CoV. Herein, we suggest four potential drug candidates (an ACE2-based peptide, remdesivir, 3CLpro-1 and a novel vinylsulfone protease inhibitor) that could be used to treat patients suffering with the 2019-nCoV. We also summarize previous efforts into drugging these targets and hope to help in the development of broad-spectrum anti-coronaviral agents for future epidemics.
由于目前 2019-nCoV 爆发的轨迹未知,公共卫生和医疗措施都将需要用来控制病毒的传播并优化患者的预后。尽管人们对该病毒知之甚少,但对其基因组序列的检查表明,它与其研究得更好的表亲 SARS-CoV 具有很强的同源性。用于宿主细胞感染的刺突蛋白显示出关键的非同义突变,这可能会影响以前开发的治疗药物的疗效,但仍然是生物制剂和大环肽的可行靶标。其他关键的药物靶点,包括 RNA 依赖性 RNA 聚合酶和冠状病毒主要蛋白酶(3CLpro),与 SARS-CoV 的同源性高达 95%以上。在此,我们提出了四种可能的药物候选物(基于 ACE2 的肽、瑞德西韦、3CLpro-1 和新型乙烯砜蛋白酶抑制剂),可用于治疗感染 2019-nCoV 的患者。我们还总结了以前针对这些靶点的药物研发工作,并希望有助于开发针对未来流行的广谱抗冠状病毒药物。