Your browser doesn't support javascript.
loading
CavitOmiX Drug Discovery: Engineering Antivirals with Enhanced Spectrum and Reduced Side Effects for Arboviral Diseases.
Parigger, Lena; Krassnigg, Andreas; Hetmann, Michael; Hofmann, Anna; Gruber, Karl; Steinkellner, Georg; Gruber, Christian C.
Afiliación
  • Parigger L; Innophore GmbH, 8010 Graz, Austria.
  • Krassnigg A; Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
  • Hetmann M; Innophore GmbH, 8010 Graz, Austria.
  • Hofmann A; Innophore GmbH, 8010 Graz, Austria.
  • Gruber K; Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
  • Steinkellner G; Innophore GmbH, 8010 Graz, Austria.
  • Gruber CC; Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
Viruses ; 16(8)2024 Jul 24.
Article en En | MEDLINE | ID: mdl-39205160
ABSTRACT
Advancing climate change increases the risk of future infectious disease outbreaks, particularly of zoonotic diseases, by affecting the abundance and spread of viral vectors. Concerningly, there are currently no approved drugs for some relevant diseases, such as the arboviral diseases chikungunya, dengue or zika. The development of novel inhibitors takes 10-15 years to reach the market and faces critical challenges in preclinical and clinical trials, with approximately 30% of trials failing due to side effects. As an early response to emerging infectious diseases, CavitOmiX allows for a rapid computational screening of databases containing 3D point-clouds representing binding sites of approved drugs to identify candidates for off-label use. This process, known as drug repurposing, reduces the time and cost of regulatory approval. Here, we present potential approved drug candidates for off-label use, targeting the ADP-ribose binding site of Alphavirus chikungunya non-structural protein 3. Additionally, we demonstrate a novel in silico drug design approach, considering potential side effects at the earliest stages of drug development. We use a genetic algorithm to iteratively refine potential inhibitors for (i) reduced off-target activity and (ii) improved binding to different viral variants or across related viral species, to provide broad-spectrum and safe antivirals for the future.
Asunto(s)
Palabras clave

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Antivirales / Infecciones por Arbovirus / Descubrimiento de Drogas Idioma: En Revista: Viruses Año: 2024 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Antivirales / Infecciones por Arbovirus / Descubrimiento de Drogas Idioma: En Revista: Viruses Año: 2024 Tipo del documento: Article