Homo-harringtonine (HHT) is highly effective against SARS-CoV-2-A potential first-line defense in future coronavirus epidemics

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 in large scale by nasal spray, is based on Homo-harringtonine (HHT) that has been approved for treating other diseases. HHT blocked protein elongation and repressed in vitro replication of all 4 coronaviruses (including SARS-CoV-2) tested at the nano-molar concentration, demonstrating its potential of broad effectiveness against coronaviruses. In animal models, HHT cleared SARS-CoV-2 in all treated mice in 3 days by daily nasal dripping of a small dose (40 ug). 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 3/4 six 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 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.