Homo-harringtonine (HHT) – A highly effective drug against coronaviruses and the potential for large-scale clinical applications

Wen, Hai-Jun; Lin, Pei; Zhong, Gong-Xun; Xu, Zhi-Chao; Shuai, Lei; Wen, Zhi-Yuan; Wang, Chong; Cao, Xue; He, Wen-Bin; Feng, Jing; Cai, Qi-Chun; Ma, Hua-Juan; Wu, Si-Jin; Wang, Guo-Dong; Lyu, Xue-Mei; Liu, Feng-Liang; Zheng, Yong-Tang; Zeng, Hui; He, Xiong-Lei; Chen, Hualan; Zhang, Fu-Jie; Wu, Chung-I

In the search for treatment schemes of COVID-19, we start by examining the general weakness of coronaviruses and then identify approved drugs attacking that weakness. The approach, if successful, should identify drugs with a specific mechanism that is at least as effective as the best drugs proposed and are ready for clinical trials. All coronaviruses translate their non-structural proteins (∼16) in concatenation, resulting in a very large super-protein. Homo-harringtonine (HHT), which has been approved for the treatment of leukemia, blocks protein elongation very effectively. Hence, HHT can repress the replication of many coronaviruses at the nano-molar concentration. In two mouse models, HHT clears SARS-CoV-2 in 3 days, especially by nasal dripping of 40 ug per day. We also use dogs to confirm the safety of HHT delivered by nebulization. The nebulization scheme could be ready for large-scale applications at the onset of the next epidemics. For the current COVID-19, a clinical trial has been approved by the Ditan hospital of Beijing but could not be implemented for want of patients. The protocol is available to qualified medical facilities.