{"doi":"10.1101/2021.01.27.428428","title":"Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model","abstract":"ABSTRACT The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the defining global health emergency of this century. GC-376 is a M pro inhibitor with antiviral activity against SARS-CoV-2 in vitro . Using the K18-hACE2 mouse model, the in vivo antiviral efficacy of GC-376 against SARS-CoV-2 was evaluated. GC-376 treatment was not toxic in K18-hACE2 mice and produced milder tissue lesions, reduced viral loads, fewer presence of viral antigen, and reduced inflammation in comparison to vehicle-treated controls, most notably in the brain in mice challenged with a low virus dose. Although GC-376 was not sufficient to improve neither clinical symptoms nor survival, it did show a positive effect against SARS-CoV-2 in vivo . This study supports the notion that the K18-hACE2 mouse model is suitable to study antiviral therapies against SARS-CoV-2, and GC-376 represents a promising lead candidate for further development to treat SARS-CoV-2 infection.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":213745,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":655210,"name":"Stivalis Cárdenas-García","orcid":"0000-0002-7613-8642","position":1,"is_corresponding":false},{"id":655211,"name":"Silvia Carnaccini","orcid":"0000-0002-1656-4068","position":2,"is_corresponding":false},{"id":655212,"name":"Brittany Seibert","orcid":"0000-0002-5721-5382","position":3,"is_corresponding":false},{"id":655213,"name":"Daniela S. Rajão","orcid":"0000-0002-0772-0065","position":4,"is_corresponding":false},{"id":107696,"name":"Jun Wang","orcid":"0000-0002-4845-4621","position":5,"is_corresponding":false},{"id":399634,"name":"Daniel R. Pérez","orcid":"0000-0002-6569-5689","position":6,"is_corresponding":false},{"id":655209,"name":"C. Joaquín Cáceres","orcid":"0000-0001-8508-6592","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-18T23:52:41.672172Z","pmid":"33532776","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}