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

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 in vitro 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.