A small-molecule SARS-CoV-2 inhibitor targeting the membrane protein

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Abstract The membrane (M) protein of betacoronaviruses is well conserved and has a key role in viral assembly 1,2 . Here we describe the identification JNJ-9676, small-molecule inhibitor targeting coronavirus M protein. JNJ-9676 demonstrates vitro nanomolar antiviral activity against SARS-CoV-2, SARS-CoV sarbecovirus strains from bat pangolin zoonotic origin. Using cryogenic electron microscopy (cryo-EM), determined binding pocket formed by transmembrane domains dimer. Compound stabilized dimer an altered conformational state between its long short forms, preventing release infectious virus. In pre-exposure Syrian golden hamster model, (25 mg per kg twice day) showed excellent efficacy, illustrated significant reduction load virus lung 3.5 4 log 10 -transformed RNA copies 50% tissue culture infective dose (TCID 50 ) lung, respectively. Histopathology scores at this were reduced to baseline. post-exposure was efficacious 75 day even when added 48 h after infection, peak loads observed. attractive target block replication, represents interesting chemical series towards identifying clinical candidates addressing current future pandemics.

Language: Английский

AI/ML methodologies and the future-will they be successful in designing the next generation of new chemical entities?

Journal of Cheminformatics, Journal Year: 2025, Volume and Issue: 17(1)

Published: April 6, 2025

Cheminformatics and chemical databases are essential to drug discovery. However, machine learning (ML) artificial intelligence (AI) methodologies changing the way in which data is used. How will use of change discovery moving forward? do new ML methods molecular property prediction, hit lead target identification structure prediction differ compare with previous computational methods? Will improve diversity ligand design, offer enhancements. There still many advantages physics based they something lacking ML/ AI methods. Additionally, training often give best results when experimental assay measurements fed back into model. Often modeling not diametrically opposed but greatest advantage used complementary.

Language: Английский

Meeting report: Seventh Summer School on Innovative Approaches for Identification of Antiviral Agents (IAAASS).

Antiviral Research, Journal Year: 2025, Volume and Issue: unknown, P. 106170 - 106170

Published: April 1, 2025

Language: Английский