{"doi":"10.1101/2020.07.31.231274","title":"Force-dependent stimulation of RNA unwinding by SARS-CoV-2 nsp13 helicase","abstract":"The superfamily-1 helicase non-structural protein 13 (nsp13) is required for SARS-CoV-2 replication, making it an important antiviral therapeutic target. The mechanism and regulation of nsp13 has not been explored at the single-molecule level. Specifically, force-dependent unwinding experiments have yet to be performed for any coronavirus helicase. Here, using optical tweezers, we find that nsp13 unwinding frequency, processivity, and velocity increase substantially when a destabilizing force is applied to the dsRNA, suggesting a passive unwinding mechanism. These results, along with bulk assays, depict nsp13 as an intrinsically weak helicase that can be potently activated by picoNewton forces. Such force-dependent behavior contrasts the known behavior of other viral monomeric helicases, drawing stronger parallels to ring-shaped helicases. Our findings suggest that mechanoregulation, which may be provided by a directly bound RNA-dependent RNA polymerase, enables on-demand helicase activity on the relevant polynucleotide substrate during viral replication.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":120729,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9584,"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":315770,"name":"Patrick M. M. Shelton","orcid":null,"position":1,"is_corresponding":false},{"id":313625,"name":"Michael Grasso","orcid":"0000-0002-2076-867X","position":2,"is_corresponding":false},{"id":315771,"name":"Xiaocong Cao","orcid":null,"position":3,"is_corresponding":false},{"id":313626,"name":"Sara Warrington","orcid":"0000-0002-8049-0585","position":4,"is_corresponding":false},{"id":313627,"name":"Amol Aher","orcid":"0000-0002-5283-5259","position":5,"is_corresponding":false},{"id":279313,"name":"Shixin Liu","orcid":"0000-0003-4238-7066","position":6,"is_corresponding":false},{"id":313628,"name":"Tarun M. Kapoor","orcid":"0000-0003-0628-211X","position":7,"is_corresponding":false},{"id":313624,"name":"Keith J. Mickolajczyk","orcid":"0000-0001-9445-0325","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-18T23:14:38.147936Z","pmid":"32766580","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":[]}