Warning: This is a preliminary report that has not been peer-reviewed. It should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information.

Duple extinguishment of COVID-19: single compound synergized inhibition of SARS-CoV-2 replication and direct suppression of inflammatory cytokines in vitro/vivo (Preliminary Report)

The virus replication and lung inflammation are basic targets for COVID-19 treatment. To effectively treat COVID-19, the best chemical drug should combine inhibition of SARS-CoV-2 replication and direct suppression of inflammatory cytokine expression together. Our SARS-CoV-2 main protease (Mpro) crystal structure studies revealed Au(I), derived from auranofin (AF) or gold ...
cluster (GA), could specifically bind thiolate of Cys145 of SARS-CoV-2 Mpro. GA or AF could well inhibit Mpro activity and significantly decrease SARS-CoV-2 replication in cell. Cell studies showed that either AF or GA could down-regulate NF{kappa}B pathway, therefore significantly inhibit inflammatory cytokine level of IL-6, IL-1{beta}, TNF- in macrophage and bronchial epithelial cell, respectively. The lung viral load in GA treated COVID-19 mice (15mg/kg.bw) is significantly lower than that in normal saline (NS, 0.9% NaCl) treated COVID-19 mice, and pathological studies revealed GA treatment (score ~1.8) significantly reduced lung inflammatory injury compared with NS treated COVID-19 mice (score ~3). After normal mice were treated by GA (15mg/kg), the Au ingredient well distributed into lungs and there are no pathological changes in main organs when compared with control mice. The toxicity results revealed GA is more safety than auranofin for cell/mice/rat. The rat pharmacokinetics studies show GA is with high bioavailability (> 90%) in vivo.One Sentence SummarySingle gold compound not only significantly inhibits SARS-CoV-2 replication in lung and but also directly suppress lung inflammatory injury in COVID-19 mice, it is with great potential to effectively treat COVID-19.
Date: Oct. 16, 2020
Status: Preliminary Report
Download Curated Data For This Publication
225993
Switch View:
  • Interactions 1