A proposal for clinical trials of COVID-19 treatment using homo-harringtonine

A scheme for treating COVID-19 was published in NSR in April [1] based on blocking the translation of very large viral proteins. Since then, additional supporting data have greatly strengthened the proposal. The drug, HHT (homoharringtonine, or omacetaxine), is readily available and inexpensive as it has been approved since 2012 for treating leukemia. The in vitro and in vivo data clearly justify the planning of clinical trials. Given the specificmechanism, we believe a trial of modest scale would be sufficient to prove, or disprove, the efficacy of the treatment scheme. Such trials, however, are only feasible in regions with many new infections. This letter, commenting on Wu and Wen [1], has an expanded authorship that includes physicians with first-hand experience in treating COVID-19 patients and virologists with recent publications on SARS-CoV-2. We wish to bring this proposal to the attentionof the global community as there are few new cases in China for such trials.

[1]  G. Guyatt,et al.  Drug treatments for covid-19: living systematic review and network meta-analysis , 2020, BMJ.

[2]  R. Bruno,et al.  Remdesivir for 5 or 10 Days in Patients with Severe Covid-19 , 2020, The New England journal of medicine.

[3]  J. Qu,et al.  Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial , 2020, BMJ.

[4]  H. Shan,et al.  Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19 , 2020, medRxiv.

[5]  Kwok-Hung Chan,et al.  Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial , 2020, The Lancet.

[6]  Benjamin J. Polacco,et al.  A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug-Repurposing , 2020, Nature.

[7]  Xuhui Huang,et al.  Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro , 2020, Antiviral Research.

[8]  P. Vollmar,et al.  Virological assessment of hospitalized patients with COVID-2019 , 2020, Nature.

[9]  Bin Zhang,et al.  Treatment With Convalescent Plasma for Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection , 2020, Chest.

[10]  Yuan Wei,et al.  A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19 , 2020, The New England journal of medicine.

[11]  Eric H. Y. Lau,et al.  Temporal dynamics in viral shedding and transmissibility of COVID-19 , 2020, Nature Medicine.

[12]  G. Kampf,et al.  Efficient inactivation of SARS-CoV-2 by WHO-recommended hand rub formulations and alcohols , 2020, bioRxiv.

[13]  M. Poo,et al.  Moral imperative for immediate release of 2019-nCoV sequence data , 2020, National science review.

[14]  M. Wise,et al.  Potential Role of Oral Rinses Targeting the Viral Lipid Envelope in SARS-CoV-2 Infection , 2020, Function.

[15]  T. Tenson,et al.  Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine , 2019, Viruses.

[16]  S. Allesina,et al.  Gene regulatory network stabilized by pervasive weak repressions: microRNA functions revealed by the May–Wigner theory , 2019, National science review.

[17]  Kazuyuki Aihara,et al.  Detection for disease tipping points by landscape dynamic network biomarkers , 2018, National science review.

[18]  Wen Meng,et al.  The Natural Compound Homoharringtonine Presents Broad Antiviral Activity In Vitro and In Vivo , 2018, Viruses.

[19]  Xuming Zhang,et al.  A screen of the NIH Clinical Collection small molecule library identifies potential anti-coronavirus drugs , 2014, Antiviral Research.

[20]  Marina V. Rodnina,et al.  Structural basis for the inhibition of the eukaryotic ribosome , 2014, Nature.

[21]  Justin Jang Hann Chu,et al.  Inhibition of Chikungunya Virus Replication by Harringtonine, a Novel Antiviral That Suppresses Viral Protein Expression , 2012, Antimicrobial Agents and Chemotherapy.

[22]  J. Nemunaitis,et al.  Pharmacokinetic study of omacetaxine mepesuccinate administered subcutaneously to patients with advanced solid and hematologic tumors , 2012, Cancer Chemotherapy and Pharmacology.

[23]  B. Giraudeau,et al.  Aerosolized gemcitabine in patients with carcinoma of the lung: feasibility and safety study. , 2011, Journal of aerosol medicine and pulmonary drug delivery.

[24]  R. Pazdur,et al.  U.S. Food and Drug Administration approval summary: omacetaxine mepesuccinate as treatment for chronic myeloid leukemia. , 2014, The oncologist.

[25]  T. Siu,et al.  Quantitation of homoharringtonine in plasma by high-performance liquid chromatography with amperometric detection. , 1989, Journal of chromatography.

[26]  M. Fresno,et al.  Inhibition of translation in eukaryotic systems by harringtonine. , 1977, European journal of biochemistry.