Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic Potential

Original Article: Jimin Xu, et al, Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic Potential, ACS Infect. Dis.

Author of summary: Alessandro Fracassi; Reviewer: Francesca Fontana

Orgiinal Article Published on March 3rd, 2020

Drug repurposing screenings identified niclosamide, an FDA-approved anthelminthic drug, as a candidate drug against SARS-CoV and MERS-CoV. A review by Xu et al on the antiviral activity of niclosamide, focusing on its potential use in the treatment of COVID-19.

Niclosamide is an FDA-approved anthelminthic drug that exerts its anticestodal effect by inhibiting oxidative phosphorylation and stimulating adenosine triphosphatase activity in the mitochondria. Over the past several years, niclosamide has been identified as a multifunctional drug via drug repurposing screens, indicating its potential to treat other human diseases.

In this review, the authors report evidence pertinent to its potential use against COVID-19.

In vitro, niclosamide was shown to inhibit SARS-CoV replication. Wu et al showed a block in the synthesis of viral antigens, recognized by an immunoassay with patient-derived serum, at doses of 1.56 μM or higher of niclosamide (3.12 μM by RT-PCR). Furthermore, others confirmed that niclosamide was able to suppress the cytopathic effect of SARS-CoV and its replication at low-micromolar doses.

Regarding the mechanism of action, unlike other drugs such as 2-chloro-4-nitroanilide, niclosamide showed no obvious inhibitory activity against SARS-CoV 3CL protease up to 50 μM, indicating that it may exert its anti-SARS activity via a different mechanism of action.

Instead, in MERS-CoV infection, Gassen et al showed that low-micromolar doses of niclosamide could re-activate autophagy, stabilize Beclin 1, and reduce viral replication of MERS-CoV. Nevertheless, since niclosamide is a multifunctional drug, it cannot be excluded that the anti-MERS activity is exerted by regulating other targets than the SKP2/Beclin1 pathway.

Based on its broad antiviral properties and the evidence on the beta-coronavirus SARS-CoV and MERS, the authors suggest that niclosamide, an inexpensive and well-tolerated old drug, may be repurposed for the treatment COVID-19, and should be further investigated.

Bibliography:

Wu CJ, Jan JT, Chen CM, Hsieh HP, Hwang DR, Liu HW, Liu CY, Huang HW, Chen SC, Hong CF, Lin RK, Chao YS, Hsu JT. Inhibition of severe acute respiratory syndrome coronavirus replication by niclosamide. Antimicrob Agents Chemother. 2004 Jul;48(7):2693-6.

Gassen NC, Niemeyer D, Muth D, Corman VM, Martinelli S, Gassen A, Hafner K, Papies J, Mösbauer K, Zellner A, Zannas AS, Herrmann A, Holsboer F, Brack-Werner R, Boshart M, Müller-Myhsok B, Drosten C, Müller MA, Rein T. SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection. Nat Commun. 2019 Dec 18;10(1):5770.

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