Interferon-β and mycophenolic acid are potent inhibitors of middle east respiratory syndrome coronavirus in cell-based assays
JournalJournal of General Virology
MetadataShow full item record
AbstractThe Middle East respiratory syndrome coronavirus (MERS-CoV) presents a novel emerging threat to public health worldwide. Several treatments for infected individuals have been suggested including IFN, ribavirin and passive immunotherapy with convalescent plasma. Administration of IFN-α2b and ribavirin has improved outcomes of MERS-CoV infection in rhesus macaques when administered within 8 h post-challenge. However, detailed and systematic evidence on the activity of other clinically available drugs is limited. Here we compared the susceptibility of MERS-CoV with different IFN products (IFN-α2b, IFN-γ, IFN-universal, IFN-α2a and IFN-β), as well as with two antivirals, ribavirin and mycophenolic acid (MPA), against MERS-CoV (Hu/Jordan-N3/2012) in vitro. Of all the IFNs tested, IFN-β showed the strongst inhibition of MERS-CoV in vitro, with an IC50 of 1.37 U ml−1, 41 times lower than the previously reported IC50 (56.08 U ml−1) of IFN-α2b. IFN-β inhibition was confirmed in the virus yield reduction assay, with an IC90 of 38.8 U ml−1. Ribavirin did not inhibit viral replication in vitro at a dose that would be applicable to current treatment protocols in humans. In contrast, MPA showed strong inhibition, with an IC50 of 2.87 µM. This drug has not been previously tested against MERS-CoV and may provide an alternative to ribavirin for treatment of MERS-CoV. In conclusion, IFN-β, MPA or a combination of the two may be beneficial in the treatment of MERS-CoV or as a post-exposure intervention in high-risk patients with known exposures to MERS-CoV.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84894028391&doi=10.1099%2fvir.0.061911-0&partnerID=40&md5=c98e55d0b03cc742bace28668bc2122f; http://hdl.handle.net/10713/12412
- Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus.
- Authors: Chan JF, Chan KH, Kao RY, To KK, Zheng BJ, Li CP, Li PT, Dai J, Mok FK, Chen H, Hayden FG, Yuen KY
- Issue date: 2013 Dec
- Antiviral Activity of Type I, II, and III Interferons Counterbalances ACE2 Inducibility and Restricts SARS-CoV-2.
- Authors: Busnadiego I, Fernbach S, Pohl MO, Karakus U, Huber M, Trkola A, Stertz S, Hale BG
- Issue date: 2020 Sep 10
- Small-Molecule Antiviral β-d-<i>N</i> <sup>4</sup>-Hydroxycytidine Inhibits a Proofreading-Intact Coronavirus with a High Genetic Barrier to Resistance.
- Authors: Agostini ML, Pruijssers AJ, Chappell JD, Gribble J, Lu X, Andres EL, Bluemling GR, Lockwood MA, Sheahan TP, Sims AC, Natchus MG, Saindane M, Kolykhalov AA, Painter GR, Baric RS, Denison MR
- Issue date: 2019 Dec 15
- Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques.
- Authors: Falzarano D, de Wit E, Rasmussen AL, Feldmann F, Okumura A, Scott DP, Brining D, Bushmaker T, Martellaro C, Baseler L, Benecke AG, Katze MG, Munster VJ, Feldmann H
- Issue date: 2013 Oct
- Engineering a replication-competent, propagation-defective Middle East respiratory syndrome coronavirus as a vaccine candidate.
- Authors: Almazán F, DeDiego ML, Sola I, Zuñiga S, Nieto-Torres JL, Marquez-Jurado S, Andrés G, Enjuanes L
- Issue date: 2013 Sep 10