{"doi":"10.1101/2020.05.15.098731","title":"Favipiravir strikes the SARS-CoV-2 at its Achilles heel, the RNA polymerase","abstract":"The ongoing Corona Virus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emphasized the urgent need for antiviral therapeutics. The viral RNA-dependent-RNA-polymerase (RdRp) is a promising target with polymerase inhibitors successfully used for the treatment of several viral diseases. Here we show that Favipiravir exerts an antiviral effect as a nucleotide analogue through a combination of chain termination, slowed RNA synthesis and lethal mutagenesis. The SARS-CoV RdRp complex is at least 10-fold more active than any other viral RdRp known. It possesses both unusually high nucleotide incorporation rates and high-error rates allowing facile insertion of Favipiravir into viral RNA, provoking C-to-U and G-to-A transitions in the already low cytosine content SARS-CoV-2 genome. The coronavirus RdRp complex represents an Achilles heel for SARS-CoV, supporting nucleoside analogues as promising candidates for the treatment of COVID-19.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":118326,"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":113,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.959,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":235134,"name":"Barbara Selisko","orcid":"0000-0001-7135-4357","position":1,"is_corresponding":false},{"id":551247,"name":"NTT Le","orcid":null,"position":2,"is_corresponding":false},{"id":235136,"name":"Johanna Huchting","orcid":"0000-0001-6368-3273","position":3,"is_corresponding":false},{"id":235137,"name":"Franck Touret","orcid":"0000-0002-4734-2249","position":4,"is_corresponding":false},{"id":235138,"name":"Géraldine Piorkowski","orcid":"0000-0001-5023-855X","position":5,"is_corresponding":false},{"id":235139,"name":"Véronique Fattorini","orcid":"0000-0001-6420-7949","position":6,"is_corresponding":false},{"id":235140,"name":"François Ferrón","orcid":"0000-0002-8351-4992","position":7,"is_corresponding":false},{"id":235141,"name":"Étienne Decroly","orcid":"0000-0002-6046-024X","position":8,"is_corresponding":false},{"id":235142,"name":"Chris Meier","orcid":"0000-0002-8323-5635","position":9,"is_corresponding":false},{"id":235143,"name":"Bruno Coutard","orcid":"0000-0002-2859-7123","position":10,"is_corresponding":false},{"id":235144,"name":"Olve B. Peersen","orcid":"0000-0001-6208-2660","position":11,"is_corresponding":false},{"id":235145,"name":"Bruno Canard","orcid":"0000-0003-4924-1991","position":12,"is_corresponding":false},{"id":235133,"name":"Ashleigh Shannon","orcid":"0000-0003-4290-8247","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T23:13:58.531532Z","pmid":"32511380","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":[]}