Will Auranofin Become a Golden New Treatment Against COVID-19?

Abstract

Auranofin is an FDA-approved disease-modifying anti-rheumatic drug that has been used for decades for treatment of rheumatoid arthritis. This gold(I) compound has anti-inflammatory properties because it reduces IL-6 expression via inhibition of the NF-κB-IL-6-STAT3 signaling pathway. Also, by inhibiting redox enzymes such as thioredoxin reductase, auranofin increases cellular oxidative stress and promotes apoptosis. Auranofin also possesses antiviral properties. Recently, it was reported that auranofin reduced by 95% SARS-CoV-2 RNA in infected human cells in vitro and decreased SARS-CoV-2-induced cytokine expression, including IL-6. During SARS-CoV-2 infection, a cytokine storm involving IL-6 increases severity of illness and worsens prognosis. Therefore, auranofin could, in our point of view, reduce pathology due to SARS-CoV-2-induced IL-6. COVID-19 is a rapidly-evolving respiratory disease now distributed worldwide. Strikingly high numbers of new COVID-19 cases are reported daily. We have begun a race to vaccinate people, but due to the complex logistics of this effort, the virus will continue to spread before all humans can be immunized, and new variants that may be less well contained by current vaccines are of concern. The COVID-19 pandemic has overwhelmed health care systems and new treatments to reduce mortality are urgently needed. We encourage to further evaluate the potential of auranofin in the treatment of COVID-19 in vitro and in animal models of SARS-CoV-2 infection and, if preliminary data are promising, in clinical trials with COVID-19 patients. In our opinion, auranofin has the potential to become a valuable addition to available therapies in this pandemic.

Gold-Based Metal Drugs as Inhibitors of Coronavirus Proteins: The Inhibition of SARS-CoV-2 Main Protease by Auranofin and Its Analogs

“…In fact, this drug was approved for the treatment of rheumatoid arthritis in 1988 and its safety profile is well-known and acceptable; Auranofin is currently under investigation for cancer therapy as a repurposed drug [ 35 ] and has also been proposed to fight a number of bacterial, parasitic and viral infections [ 36 ]. The potential of Auranofin as a drug for the treatment of SARS-CoV-2 recently emerged as a hot topic; a few studies demonstrated its ability to inhibit viral replication by contrasting specific enzymatic activities of the virus [ 5 , 6 , 37 ]. Auranofin could perform its antiviral activity in different ways: one of these is blocking the entry of the virus into the host cell; another is to inhibit the activity of selected viral enzymes that are crucial for virus replication and a last one is to counter host inflammatory response [ 38 ].…”

“…To this end, expanding the chemical space of the tested compounds by including a large variety of metal compounds is highly desirable. It has to be stressed that the search for efficient inhibitors of SARS-CoV-2-related proteases has almost entirely focused on organic molecules [ 2 , 3 , 4 ]; much less attention has been deserved so far to inorganic moieties [ 5 , 6 ] that merit, in our opinion, a greater consideration.…”

Next Generation Gold Drugs and Probes: Chemistry and Biomedical Applications

“…These results indicate that auranofin could be potent to limit SARS-CoV-2 infection and associated lung injury due to its antiviral, anti-inflammatory and antireactive oxygen species (ROS) properties. Further in vivo study is required to establish the safety and efficacy of auranofin for the management of SARS-CoV-2 associated disease. , …”

Metal-based strategies for the fight against COVID-19

“…Auranofin has received considerable attention 20,22,24,114,115 and was shown to inhibit replication of SARS-CoV-2 in human cells (Huh7) with an EC 50 of 1.4 mM. 88 Treatment of SARS-CoV-2 infected cells with auranofin resulted in a 95% reduction in the viral RNA 48 h post-infection.…”

“…auranofin) on inhibition inflammatory pathways and on thiol redox enzymes as well as essential viral enzymes was thought to be responsible at least partially for its anti-SARS-CoV-2 activity. 114,115 The potential inhibition of auranofin on other thiol-containing viral enzymes warrants further studies.…”