The FDA-approved gold drug Auranofin inhibits novel coronavirus (SARS-CoV-2) replication and attenuates inflammation in human cells
immunology/immunity inflammation therapeutics
Authors: Hussin A. Rothan et al.
Link to paper: https://www.biorxiv.org/content/10.1101/2020.04.14.041228v1
Journal/ Pre-Print: BioRxiv
Key Words: antirheumatic agent, viral replication, inflammation
1. Aurofin inhibits SARS-COV-2 replication using low doses in an in vitro hepatocyte model
2. Aurofin dramatically reduces virus-induced inflammation (lower levels of IL-6, TNF-a, IL-1b and NFKB in infected cells)
3. Drug treatment showed no toxicity in vitro and is considered safe for human use (further animal experiments needed)
Aurofin is an antirheumatic FDA-approved drug with low toxicity and is considered safe for humans. It works by inhibiting redox enzymes and induces ER stress and the unfolded protein response. The paper shows that viral replication in infected Huh7 cells (multiplicity of infection = 1) can be inhibited with an EC50 of approx. 1.5 μM, which means that viral RNA was reduced by 95% in 48 h. Furthermore, the study measured decreased mRNA levels of IL-6, TNF-a, IL-1b and NFKB when cells were treated with Aurofin upon infection. Taken together this suggests Aurofin as a possible drug for COVID-19 patients.
IMPACT FOR SARS-COV2/COVID19 RESEARCH EFFORTS
Understand the immune response to SARS-CoV2/COVID19
Treat of SARS-CoV2/COVID19 positive individuals: Auranofin is already FDA-approved and being produced. In patients it may reduce viral replication and inflammatory cytokines, which could be especially useful in severe cases.
· In vitro study
STRENGTHS AND LIMITATIONS OF THE PAPER
Novelty: A potential drug to treat patients that is already FDA-approved and being produced.
Standing in the field: Auranofin seems to be a recognised potential therapeutic drug in the field, as its application has already been investigated in many other diseases (including cancer, neurodegenerative disorders, HIV/AIDS, parasitic, bacterial and viral infections). It has been approved for a for phase II clinical trials for cancer therapy.
Appropriate statistics: No statistics applicable due to low number of repeats (two independent experiments conducted in duplicate each).
Viral model used: SARS-CoV-2 (USA-WA1/2020) isolated from a patient in Washington, USA (BEI NR-52281)
Translatability: There is a high translational potential, but more studies are required (animal studies have been warranted).
Main limitations: All experiments were done in Huh7 cells, which is a cancerous hepatocyte cell line. A lung cell line might have resulted in a higher relevance. Two independent experiments were done in duplicates. More experiments are needed to establish statistical power. Drug concentration for cytokine experiments was not mentioned. Virological assays very unsophisticated. Production of infectious virus should have been measured.