While　gold　compound　have　been　approved　for　Rheumatoid　arthritis　treatment　as　it　well　suppresses　inflammatory　cytokines　of　patients,　no　such　treatment　is　currently　available　for　COVID-19　treatment　in　vivo　.　We　firstly　disclose　gold　cluster　yields　better　therapeutic　outcome　than　Remdesivir　in　COVID-19　hamster　treatments　as　it　is　armed　with　direct　inhibition　viral　replication　and　intrinsic　suppression　inflammatory　cytokines　expression.　Crystal　data　reveals　that　Au　(I),　released　from　gold　cluster　(GA),　covalently　binds　thiolate　of　Cys145　of　SARS-CoV-2　M-pro.　GA　directly　decreases　SARS-CoV-2　viral　replication　and　intrinsically　down-regulates　NF　kappa　B　pathway　therefore　significantly　inhibiting　expression　of　inflammatory　cytokines　in　cells.　The　inflammatory　cytokines　in　GA-treated　COVID-19　transgenic　mice　are　found　to　be　significantly　lower　than　that　of　control　mice.　When　COVID-19　golden　hamsters　are　treated　by　GA,　the　lung　inflammatory　cytokines　levels　are　significantly　lower　than　that　of　Remdesivir.　The　pathological　results　show　that　GA　treatment　significantly　reduce　lung　inflammatory　injuries　when　compared　to　that　of　Remdesivir-treated　COVID-19　hamsters.(c)　2022　Elsevier　Ltd.　All　rights　reserved.