Homoharringtonine is a plant alkaloid derived from Cephalotoxus fortunei. It exhibits anti-tumor activity by binding to the ribosomal A site to inhibit protein translation, leading to rapid loss of short-lived proteins including Mcl-1 and c-Myc that promote the survival of leukemia cells (Dong et al., 2018; Lu and Wang, 2014). Omacetaxine, a semi-synthetic form of homoharringtonine, is approved by FDA for treatment of chronic myeloid leukemia. Homoharringtonine has also been reported to exhibit potent anti-viral activity against herpesviruses (varicella-zoster virus, herpes simplex virus-1, pseudorabies virus), coronaviruses (porcine epidemic diarrhea virus and murine hepatitis virus), rhabdoviruses (VSV and rabies virus), and other viruses (hepatitis B virus, Newcastle disease virus, and echovirus 1) (Dong et al., 2018; Andersen et al., 2019). Here, we observed homoharringtonine inhibits SARS-CoV-2 with EC50 at 2.10 μM (Fig. 1C and Table 1). Previous pharmacokinetic study showed that patients treated with 1.25 mg/m2 omacetaxine every 12 h by subcutaneous injection may reach the maximal plasma concentration at 25.1 ng/mL (0.046 μM) and 36.2 ng/mL (0.066 μM) on days 1 and 11, respectively (Nemunaitis et al., 2013), which were below the EC50 against SARS-CoV-2 virus in vitro.