homoharringtonine and nitazoxanide

In December 2019, a new coronavirus, named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), emerged from China, causing pneumonia outbreaks first in the Wuhan region and then spread worldwide. Due to a lack of efficient and specific treatments and the need to contain the epidemic, drug repurposing appears to be the most efficient tool to find a therapeutic solution.. The aim of this study was to summarize in vitro data of current agents used for the management of SARS-CoV-2 all over the world.. A literature search of articles from January 2000 until April 2020 was performed using MEDLINE, EMBASE and the Cochrane Library to assess in vitro data of current or putative therapies for SARS-CoV-2.. Although in vitro studies are scarce, data regarding chloroquine, hydroxychloroquine, remdesivir, nitazoxanide, teicoplanin, ivermectin, lopinavir, homoharringtonine, and emetine seem promising.. Scientists all over the world should work together and increase their efforts in order to find feasible and efficient solutions against this new global viral threat.

Topics: Adenosine Monophosphate; Alanine; Betacoronavirus; China; Chloroquine; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Repositioning; Emetine; Homoharringtonine; Humans; Hydroxychloroquine; Ivermectin; Lopinavir; Nitro Compounds; Pandemics; Pneumonia, Viral; SARS-CoV-2; Teicoplanin; Thiazoles

With the recent emergence of Middle East Respiratory Syndrome coronavirus in humans and the outbreak of devastating porcine epidemic diarrhea coronavirus in swine, therapeutic intervention is urgently needed. However, anti-coronavirus drugs currently are not available. In an effort to assist rapid development of anti-coronavirus drugs, here we screened the NIH Clinical Collection in cell culture using a luciferase reporter-expressing recombinant murine coronavirus. Of the 727 compounds screened, 84 were found to have a significant anti-coronavirus effect. Further experiments revealed that 51 compounds blocked virus entry while 19 others inhibited viral replication. Additional validation studies with the top 3 inhibitors (hexachlorophene, nitazoxanide and homoharringtonine) demonstrated robust anti-coronavirus activities (a reduction of 6 to 8log10 in virus titer) with an IC50 ranging from 11nM to 1.2μM. Furthermore, homoharringtonine and hexachlorophene exhibited broad antiviral activity against diverse species of human and animal coronaviruses. Since the NIH Clinical Collection consists of compounds that have already been through clinical trials, these small molecule inhibitors have a great potential for rapid development as anti-coronavirus drugs.

Topics: Animals; Antiviral Agents; Cell Line; Coronavirus; Drug Discovery; Harringtonines; Hexachlorophene; Homoharringtonine; Humans; Luciferases; Mice; Murine hepatitis virus; Nitro Compounds; Small Molecule Libraries; Thiazoles; Viral Load; Virus Internalization; Virus Replication