Usambarensine from Strychnos usambarensis: Revisiting a Bis-Indole Alkaloid for Antiviral Repositioning.

Publication date: Jun 16, 2026

Emerging RNA viruses continue to pose major global health threats, underscoring the urgent need for broad-spectrum antiviral agents. Usambarensine, a bis-indole alkaloid isolated from Strychnos usambarensis, has historically been investigated for its antimalarial and antihelminthic properties, but its antiviral potential has remained unexplored. In this study, usambarensine was isolated through bioguided fractionation and structurally confirmed by HPTLC, HPLC-UV, FT-IR, MS/MS, and NMR. The compound was first evaluated against representatives of three major RNA virus families: Coronaviridae (SARS-CoV-2), Flaviviridae (West Nile virus), and Orthomyxoviridae (Influenza A) using Vero E6 cells. Antiviral activity was quantified by RT-qPCR at 24, 48, and 72 h postinfection. Usambarensine showed strong, dose-dependent inhibition of SARS-CoV-2, achieving ∼4log reduction at 72 h, transient inhibition of West Nile virus and no significant activity against Influenza A. Based on the robust activity observed against SARS-CoV-2, screening was expanded within the Coronaviridae family to include SARS-CoV-1 and MERS-CoV, both of which yielded similar results. This selective antiviral profile, as well as the observation that viral RNA levels remain similar to the initial viral inoculum, suggests that usambarensine interferes with a coronavirus-specific early entry or fusion process, potentially involving a shared entry pathway in Vero E6 cells. These findings identify usambarensine as a promising natural product with selective antiviral activity against coronaviruses. Further mechanistic studies, including determining the specific stage of the viral replication cycle affected, elucidating the molecular target, and performing structure-activity relationship optimization, are needed to assess its potential as a lead scaffold for coronavirus entry inhibitors.

Semantics

Original Article