AI Article Synopsis

  • - The study focused on developing antiviral drugs targeting filoviruses like Ebola and Marburg during their entry stage, using a natural herb called aloperine as a starting point to create 23 new derivatives.
  • - One of these derivatives, compound 2e, showed the strongest antiviral activity in both lab tests and live models, while also demonstrating good safety and pharmacokinetics.
  • - Compound 2e works primarily by inhibiting the activity of cysteine cathepsin B, a host cell component, making it a promising candidate for broad-spectrum anti-filovirus treatment due to its unique chemical structure and effective biological mechanism.

Article Abstract

Preventing filoviruses in the entry stage is an attractive antiviral strategy. Taking aloperine, a Chinese natural herb with an endocyclic skeleton, as the lead, 23 new aloperine derivatives were synthesized and evaluated for their anti-filovirus activities including ebola virus (EBOV) and marburg virus (MARV) using pseudotyped virus model. Structure-activity relationship (SAR) analysis indicated that the introduction of a 12N-dichlorobenzyl group was beneficial for the potency. Compound 2e exhibited the most potent anti-EBOV and anti-MARV effects both in vitro and in vivo. It also displayed a good pharmacokinetic and safety profile in vivo, indicating an ideal druglike feature. The primary mechanism study showed that 2e could block a late stage of viral entry, mainly through inhibiting cysteine cathepsin B activity of host components. We consider compound 2e to be a promising broad-spectrum anti-filovirus agent with the advantages of a unique chemical scaffold and a specific biological mechanism.

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Source
http://dx.doi.org/10.1016/j.ejmech.2018.02.061DOI Listing

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