SABRes: in silico detection of drug resistance conferring mutations in subpopulations of SARS-CoV-2 genomes.
Autor: | Fong W; Centre for Infectious Diseases and Microbiology - Public Health, Westmead Hospital, NSW, Westmead, Australia. winkie.fong@health.nsw.gov.au., Rockett RJ; Centre for Infectious Diseases and Microbiology - Public Health, Westmead Hospital, NSW, Westmead, Australia.; Sydney Infectious Diseases Institute, The University of Sydney, Camperdown, NSW, Australia., Agius JE; Centre for Infectious Diseases and Microbiology - Public Health, Westmead Hospital, NSW, Westmead, Australia.; Sydney Infectious Diseases Institute, The University of Sydney, Camperdown, NSW, Australia., Chandra S; Centre for Infectious Diseases and Microbiology - Public Health, Westmead Hospital, NSW, Westmead, Australia., Johnson-Mckinnon J; Centre for Infectious Diseases and Microbiology - Public Health, Westmead Hospital, NSW, Westmead, Australia.; Sydney Infectious Diseases Institute, The University of Sydney, Camperdown, NSW, Australia., Sim E; Centre for Infectious Diseases and Microbiology - Public Health, Westmead Hospital, NSW, Westmead, Australia.; Sydney Infectious Diseases Institute, The University of Sydney, Camperdown, NSW, Australia., Lam C; Centre for Infectious Diseases and Microbiology - Public Health, Westmead Hospital, NSW, Westmead, Australia.; Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead, NSW, Australia., Arnott A; Sydney Infectious Diseases Institute, The University of Sydney, Camperdown, NSW, Australia.; Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead, NSW, Australia., Gall M; Sydney Infectious Diseases Institute, The University of Sydney, Camperdown, NSW, Australia.; Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead, NSW, Australia., Draper J; Sydney Infectious Diseases Institute, The University of Sydney, Camperdown, NSW, Australia.; Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead, NSW, Australia., Maddocks S; Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead, NSW, Australia., Chen S; Centre for Infectious Diseases and Microbiology - Public Health, Westmead Hospital, NSW, Westmead, Australia.; Sydney Infectious Diseases Institute, The University of Sydney, Camperdown, NSW, Australia.; Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead, NSW, Australia., Kok J; Sydney Infectious Diseases Institute, The University of Sydney, Camperdown, NSW, Australia.; Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead, NSW, Australia., Dwyer D; Sydney Infectious Diseases Institute, The University of Sydney, Camperdown, NSW, Australia.; Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead, NSW, Australia., O'Sullivan M; Centre for Infectious Diseases and Microbiology - Public Health, Westmead Hospital, NSW, Westmead, Australia.; Sydney Infectious Diseases Institute, The University of Sydney, Camperdown, NSW, Australia.; Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead, NSW, Australia., Sintchenko V; Centre for Infectious Diseases and Microbiology - Public Health, Westmead Hospital, NSW, Westmead, Australia.; Sydney Infectious Diseases Institute, The University of Sydney, Camperdown, NSW, Australia.; Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead, NSW, Australia. |
---|---|
Jazyk: | angličtina |
Zdroj: | BMC infectious diseases [BMC Infect Dis] 2023 May 08; Vol. 23 (1), pp. 303. Date of Electronic Publication: 2023 May 08. |
DOI: | 10.1186/s12879-023-08236-6 |
Abstrakt: | The emergence of resistance to antiviral drugs increasingly used to treat SARS-CoV-2 infections has been recognised as a significant threat to COVID-19 control. In addition, some SARS-CoV-2 variants of concern appear to be intrinsically resistant to several classes of these antiviral agents. Therefore, there is a critical need for rapid recognition of clinically relevant polymorphisms in SARS-CoV-2 genomes associated with significant reduction of drug activity in virus neutralisation experiments. Here we present SABRes, a bioinformatic tool, which leverages on expanding public datasets of SARS-CoV-2 genomes and allows detection of drug resistance mutations in consensus genomes as well as in viral subpopulations. We have applied SABRes to detect resistance-conferring mutations in 25,197 genomes generated over the course of the SARS-CoV-2 pandemic in Australia and identified 299 genomes containing resistance conferring mutations to the five antiviral therapeutics that retain effectiveness against currently circulating strains of SARS-CoV-2 - Sotrovimab, Bebtelovimab, Remdesivir, Nirmatrelvir and Molnupiravir. These genomes accounted for a 1.18% prevalence of resistant isolates discovered by SABRes, including 80 genomes with resistance conferring mutations found in viral subpopulations. Timely recognition of these mutations within subpopulations is critical as these mutations can provide an advantage under selective pressure and presents an important step forward in our ability to monitor SARS-CoV-2 drug resistance. (© 2023. Crown.) |
Databáze: | MEDLINE |
Externí odkaz: | |
Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |