Your browser doesn't support javascript.
Understanding the genetics of viral drug resistance by integrating clinical data and mining of the scientific literature.
Goto, An; Rodriguez-Esteban, Raul; Scharf, Sebastian H; Morris, Garrett M.
  • Goto A; Oxford Protein Informatics Group, Department of Statistics, University of Oxford, 24-29 St Giles', Oxford, OX1 3LB, UK.
  • Rodriguez-Esteban R; Roche Innovation Center Basel, Basel, Switzerland.
  • Scharf SH; Roche Innovation Center Basel, Basel, Switzerland.
  • Morris GM; Oxford Protein Informatics Group, Department of Statistics, University of Oxford, 24-29 St Giles', Oxford, OX1 3LB, UK. garrett.morris@stats.ox.ac.uk.
Sci Rep ; 12(1): 14476, 2022 08 25.
Article in English | MEDLINE | ID: covidwho-2008302
ABSTRACT
Drug resistance caused by mutations is a public health threat for existing and emerging viral diseases. A wealth of evidence about these mutations and their clinically associated phenotypes is scattered across the literature, but a comprehensive perspective is usually lacking. This work aimed to produce a clinically relevant view for the case of Hepatitis B virus (HBV) mutations by combining a chronic HBV clinical study with a compendium of genetic mutations systematically gathered from the scientific literature. We enriched clinical mutation data by systematically mining 2,472,725 scientific articles from PubMed Central in order to gather information about the HBV mutational landscape. By performing this analysis, we were able to identify mutational hotspots for each HBV genotype (A-E) and gene (C, X, P, S), as well as the location of disulfide bonds associated with these mutations. Through a modelling study, we also identified a mutation position common in both the clinical data and the literature that is located at the binding pocket for a known anti-HBV drug, namely entecavir. The results of this novel approach show the potential of integrated analyses to assist in the development of new drugs for viral diseases that are more robust to resistance. Such analyses should be of particular interest due to the increasing importance of viral resistance in established and emerging viruses, such as for newly developed drugs against SARS-CoV-2.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Hepatitis B, Chronic / COVID-19 Drug Treatment Type of study: Prognostic study / Reviews Limits: Humans Language: English Journal: Sci Rep Year: 2022 Document Type: Article Affiliation country: S41598-022-17746-3

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Hepatitis B, Chronic / COVID-19 Drug Treatment Type of study: Prognostic study / Reviews Limits: Humans Language: English Journal: Sci Rep Year: 2022 Document Type: Article Affiliation country: S41598-022-17746-3