{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Presley L"],"funding":["NIAID NIH HHS"],"pagination":["2616944"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12862872"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["Human TMPRSS2 is a type II transmembrane serine protease and an essential host factor for SARS-CoV-2 and influenza A virus (IAV H1N1) infections. It facilitates the cleavage of viral surface glycoproteins, which are required for membrane fusion. This importance makes it an attractive target for host-directed antiviral therapies. We previously identified N-0385 and N-0920 as nanomolar TMPRSS2 inhibitors and demonstrated their antiviral potency against several SARS-CoV-2 variants. Here, we screened another twelve N-0385/N-0920 analogs with improved pharmacokinetics. Compounds <b>9</b> and <b>10</b> showed strong inhibition of TMPRSS2 activity and viral entry: they blocked pseudoviruses and authentic SARS-CoV-2 JN.1 and IAV H1N1 in Calu-3 cells. Compound <b>9</b> displayed a synergistic effec"],"journal":["Emerging microbes & infections"],"pubmed_title":["TMPRSS2 inhibitors with broad-spectrum efficacy against SARS-CoV-2 (JN.1) and influenza A (H1N1) viruses protect mice from influenza A infection."],"pmcid":["PMC12862872"],"funding_grant_id":["DP1 AI158186","P01 AI167966","75N93022C00036"],"pubmed_authors":["Presley L","Saintigny A","Ennis S","Leduc R","Brinsden L","Villanueva I","Chen M","Fone J","Ferkova S","Veesler D","Brown JT","Jean F","Boudreault PL","McCallum M","Niikura M","Perez-Vargas J","Ho M","Thompson CAH","Kaushik N","Bautista-Sanchez D","Warner B","Olver S","Hetrick B"],"additional_accession":[]},"is_claimable":false,"name":"TMPRSS2 inhibitors with broad-spectrum efficacy against SARS-CoV-2 (JN.1) and influenza A (H1N1) viruses protect mice from influenza A infection.","description":"Human TMPRSS2 is a type II transmembrane serine protease and an essential host factor for SARS-CoV-2 and influenza A virus (IAV H1N1) infections. It facilitates the cleavage of viral surface glycoproteins, which are required for membrane fusion. This importance makes it an attractive target for host-directed antiviral therapies. We previously identified N-0385 and N-0920 as nanomolar TMPRSS2 inhibitors and demonstrated their antiviral potency against several SARS-CoV-2 variants. Here, we screened another twelve N-0385/N-0920 analogs with improved pharmacokinetics. Compounds <b>9</b> and <b>10</b> showed strong inhibition of TMPRSS2 activity and viral entry: they blocked pseudoviruses and authentic SARS-CoV-2 JN.1 and IAV H1N1 in Calu-3 cells. Compound <b>9</b> displayed a synergistic effec","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Dec","modification":"2026-07-14T21:27:13.233Z","creation":"2026-06-25T03:08:01.869Z"},"accession":"S-EPMC12862872","cross_references":{"pubmed":["41612887"],"doi":["10.1080/22221751.2026.2616944"]}}