Homoharringtonine is highly effective against SARS-CoV-2: a potential first-line defense in future coronavirus epidemics

As COVID-19 is the third coronavirus epidemic in this century, it would be desirable to have a treatment scheme in anticipation of a fourth one. We here present a scheme that could clear SARS-CoV-2 in 2-4 days post-infection from the upper respiratory tract (URT), where the virions are initially concentrated. The scheme, applicable on a large scale by nasal spray, is based on homoharringtonine (HHT), which has been approved for treating other diseases. HHT blocked protein elongation and repressed <i>in vitro</i> replication of all four coronaviruses (including SARS-CoV-2) that were tested at the nano-molar concentration, demonstrating its potential for broad effectiveness against coronaviruses. In animal models, HHT cleared SARS-CoV-2 in all treated mice within 3 days by daily nasal dripping of a small dose (40 μg). In December 2022, HHT was administered to 26 cancer patients by nebulization at 1 mg/day. On average, the viral load in the URT was reduced by three-quarters 6 hours after the nebulization. In the wavelet of May 2023, 11 patients without other medical conditions were administered HHT by repeated liquid nasal spray at the low total daily dose of 0.2 mg. Ten of the 11 patients were cleared of the virus in 2-4 days. In comparison, in large-cohort studies of participants in China during the same wave, most patients need 7-9 days to turn negative. No adverse effects were detected in any patient in the two clinical trials. A short review of drugs approved for treating COVID-19 shows the many advantages of HHT. With continual development, it could become a first-line defense at the onset of future coronavirus epidemics.

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Journal
National Science Review
Published
2024-10-25
DOI
https://doi.org/10.1093/nsr/nwae382
Primary Topic
Synthesis and biological activity
Type
article
Field-Weighted Citation Impact
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article

Homoharringtonine is highly effective against SARS-CoV-2: a potential first-line defense in future coronavirus epidemics

Guang-An Lu, Xue Cao, Hui Zeng, XingQian Lai et al.
National Science Review
Synthesis and biological activity
article

Homoharringtonine is highly effective against SARS-CoV-2: a potential first-line defense in future coronavirus epidemics

Guang-An Lu, Xue Cao, Hui Zeng, XingQian Lai, Xue Liu, Manli Wang, Fujie Zhang, Miles E Tracy, Sijin Wu, Tian‐Zhang Song, Xionglei He, Xue-Mei Lyu, Ao Ding, Hualan Chen, Gongxun Zhong, Feng‐Liang Liu, Wenbin He, Jian Li, Guodong Wang, Jiao Guo, Jiasheng Li, Zhìhóng Hú, Jing Feng, Wen Zeng, Zhichao Xu, Chung-I Wu, Changhao Shi, Yongjie Yao, Ge Zhang, Hua-Juan Ma, Haijun Wen, Qi-Chun Cai, Wei Chen, Xi Wang
article en

Abstract

As COVID-19 is the third coronavirus epidemic in this century, it would be desirable to have a treatment scheme in anticipation of a fourth one. We here present a scheme that could clear SARS-CoV-2 in 2-4 days post-infection from the upper respiratory tract (URT), where the virions are initially concentrated. The scheme, applicable on a large scale by nasal spray, is based on homoharringtonine (HHT), which has been approved for treating other diseases. HHT blocked protein elongation and repressed <i>in vitro</i> replication of all four coronaviruses (including SARS-CoV-2) that were tested at the nano-molar concentration, demonstrating its potential for broad effectiveness against coronaviruses. In animal models, HHT cleared SARS-CoV-2 in all treated mice within 3 days by daily nasal dripping of a small dose (40 μg). In December 2022, HHT was administered to 26 cancer patients by nebulization at 1 mg/day. On average, the viral load in the URT was reduced by three-quarters 6 hours after the nebulization. In the wavelet of May 2023, 11 patients without other medical conditions were administered HHT by repeated liquid nasal spray at the low total daily dose of 0.2 mg. Ten of the 11 patients were cleared of the virus in 2-4 days. In comparison, in large-cohort studies of participants in China during the same wave, most patients need 7-9 days to turn negative. No adverse effects were detected in any patient in the two clinical trials. A short review of drugs approved for treating COVID-19 shows the many advantages of HHT. With continual development, it could become a first-line defense at the onset of future coronavirus epidemics.

National Science ReviewVol. 12(11)
Sun Yat-sen University (CN), Jinan University (CN), Capital Medical University (CN), Kunming Institute of Zoology (CN), Biocon (Switzerland) (CH), Chinese Academy of Sciences (CN), Kunming Medical University (CN), Fuda Cancer Hospital (CN), Southern University of Science and Technology (CN), Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) (CN), Wuhan Institute of Virology (CN), Chinese Academy of Agricultural Sciences (CN), Southern Medical University Shenzhen Hospital (CN), Beijing Ditan Hospital (CN), Hangzhou Special Equipment Inspection and Research Institute (CN), Shenzhen Second People's Hospital (CN), Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai) (CN), Xi’an Jiaotong-Liverpool University (CN), Harbin Veterinary Research Institute (CN)
National Natural Science Foundation of China, University of Ruhuna
Good health and well-being
Openalex Percentile: Top 86%
Synthesis and biological activity
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