Hypericin Suppresses SARS-CoV-2 Replication and Synergizes with Antivirals via Dual Targeting of RdRp and 3CLpro

The continuous emergence of SARS-CoV-2 variants underscores the need for novel antiviral candidates. Hypericin (HY), a compound derived from <i>Hypericum perforatum</i>, exhibited potent in vitro activity against SARS-CoV-2 in Vero E6 cells, with low cytotoxicity (CC<sub>50</sub...

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Main Authors: Helena da Silva Souza, Jéssica Santa Cruz Carvalho Martins, Thiagos das Chagas Sousa, Saiqa Sardar, Natalia Fintelman-Rodrigues, Lina Silva-Trujillo, Thiago Moreno Lopes e Souza, Marilda Mendonça Siqueira, Jorge Hernandes Fernandes, Aline da Rocha Matos
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/13/5/1004
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Summary:The continuous emergence of SARS-CoV-2 variants underscores the need for novel antiviral candidates. Hypericin (HY), a compound derived from <i>Hypericum perforatum</i>, exhibited potent in vitro activity against SARS-CoV-2 in Vero E6 cells, with low cytotoxicity (CC<sub>50</sub> > 200 nM). HY showed no significant activity against Influenza A (H1N1) or dengue virus serotype 2, supporting its selective action. Antiviral effects were most evident when HY was administered post-infection, in a concentration-dependent manner, while cellular pretreatment or viral pre-incubation produced limited effects. Notably, HY also displayed virucidal activity, significantly reducing viral titers at 4 °C, 22 °C, and 37 °C. Combination treatments with remdesivir or nirmatrelvir enhanced antiviral efficacy by 50–70% relative to monotherapy, depending on compound concentration. Molecular simulations revealed stable interactions with conserved residues in RdRp and 3CLpro, suggesting a low risk of resistance. Together, these findings highlight the potential of HY as a selective antiviral and virucidal agent against SARS-CoV-2, particularly in combination regimens.
ISSN:2076-2607