A screen of the NIH Clinical Collection small molecule library identifies potential anti-coronavirus drugs.
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.
['Cao|Jianzhong|J|', 'Forrest|J Craig|JC|', 'Zhang|Xuming|X|']
D000818:Animals D000998:Antiviral Agents D002460:Cell Line D017934:Coronavirus D055808:Drug Discovery D006248:Harringtonines D006582:Hexachlorophene D000077863:Homoharringtonine D006801:Humans D008156:Luciferases D051379:Mice D006517:Murine hepatitis virus D009574:Nitro Compounds D054852:Small Molecule Libraries D013844:Thiazoles D019562:Viral Load D053586:Virus Internalization D014779:Virus Replication
Screening Small molecule Coronavirus NCC library