Coronavirus (SARS-CoV-2) – Potential use of HSP90 inhibitors as therapeutic agents against COVID-19?

An article by Li et al. published in 2004 reported in vitro experiments showing that geldanamycin was effective against SARS CoV at high submicromolar/low micromolar concentrations. The article also demonstrated that geldanamycin was active against multiple DNA and RNA viruses. See also the articles by Li et al. (2012) and Connor et al. (2007).

HSP90 inhibitors have long been of interest as potential anti-cancer therapeutics. The natural products geldanamycin and radicicol had issues of aqueous solubility, stability and hepatotoxicity in animals (geldanamycin). A large number of more suitable analogs of geldanamycin and radicicol were prepared, and synthetic small molecule and peptide inhibitors were developed. Many of these HSP90 inhibitors were tested in clinical trials as single agents or in combination with other active agents [Sidera and Patsavoudi (2014); Kryeziu et al. (2019)].

Considering that geldanamycin was reported to be active against SARS-CoV, that the compound exhibits a broad spectrum of antiviral activities as well as that clinically tested inhibitors are available, it may be reasonable to investigate HSP90 inhibitors as potential therapeutic agents against SARS-CoV-2.

Li et al. (2004) Geldanamycin, a Ligand of Heat Shock Protein 90, Inhibits the Replication of Herpes Simplex Virus Type 1 In Vitro. Antimicrob. Agents Chemother. 48: 867-872.

Li et al. (2012) Geldanamycin, a ligand of heat shock protein 90, inhibits herpes simplex virus type 2 replication both in vitro and in vivo. The J. Antibiot. 65: 509–512.

Connor et al. (2007) Antiviral activity and RNA polymerase degradation following Hsp90 inhibition in a range of negative strand viruses. Virol. 362: 109-119.

Sidera and Patsavoudi (2014) HSP90 Inhibitors: Current Development and Potential in Cancer Therapy. Recent Patents on Anti-Cancer Drug Discovery 9: 1-20.

Kryeziu et al. (2019) Combination therapies with HSP90 inhibitors against colorectal cancer. BBA – Reviews on Cancer 1871: 240-247.

HSF Pharmaceuticals does not have a commercial interest in HSP90 inhibitors.

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