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In addition, Au(I) based compounds also exhibit anti-cancer, anti-bacteria properties. The recent prevalence of the COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has aroused attention to investigate the antiviral potential of Au(I) compounds. Herein we demonstrate the pan-anti-SARS-CoV-2 activity of Au(I) metallodrugs in mammalian cells. We synthesized a panel of Au(I)-based compounds and found that these compounds could effectively inhibit the exoribonuclease and methyltransferase activities of SARS-CoV-2 nsp14\/nsp10 complex, and the ATPase and DNA unwinding activities of SARS-CoV-2 nsp13 (helicase). Mechanistic studies reveal that Au(I) can not only displace the critical Zn(II) ions from nsp14\/nsp10 complex and nsp13 but also changes the secondary and quaternary structure of nsp14 and perturbate the DNA unwinding of nsp13 by disrupting the ATP binding. This study illustrates a multi-target feature Au(I) compounds\/drug agents for the viruses, highlighting their potential as pan-anti-SARS-CoV-2 (or relevant viruses) agents.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical Abstract<\/jats:bold>\n          <\/jats:p>","DOI":"10.1007\/s00775-025-02118-9","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T08:22:10Z","timestamp":1750234930000},"page":"425-441","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Au(I)-based compounds inhibit nsp14\/nsp10 and nsp13 (helicase) to exert anti-SARS-CoV-2 properties"],"prefix":"10.1007","volume":"30","author":[{"given":"Jingxin","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueying","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Lung","family":"Chan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaiming","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuofeng","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongzhe","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"key":"2118_CR1","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/s41579-021-00630-8","volume":"19","author":"H Yang","year":"2021","unstructured":"Yang H, Rao Z (2021) Structural biology of SARS-CoV-2 and implications for therapeutic development. 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