Lectin-Based Antiviral Strategies for Porcine Reproductive and Respiratory Syndrome Virus 2 Infection: Griffithsin Suppresses Viral Replication In Vitro and Reduces Early Viremia In Vivo

Porcine reproductive and respiratory syndrome virus (PRRSV) remains a major challenge to swine production worldwide. Current vaccines have limited efficacy against genetically diverse PRRSV strains. Therefore, strategies with alternative modes of action—such as antiviral approaches that target conserved virus–host interactions, including viral attachment and entry, rather than relying solely on adaptive immune responses—are needed. We first evaluated the in vitro effect of griffithsin (GRFT), a high-mannose-binding lectin, in the monkey kidney cell line MARC-145. Cells were pre-treated with GRFT (50–200 µg/mL) prior to PRRSV infection, after which cell morphology and viral RNA replication (measured by RT-qPCR) were assessed. Pre-treatment with 100–200 µg/mL GRFT, followed by PRRSV inoculation at a multiplicity of infection of 1 or 10, reduced viral replication in MARC145 cells in a dose-dependent manner, achieving almost 100% inhibition of ORF5 and ORF7 RNA compared with untreated controls (p < 0.0001). We next investigated the in vivo effects of intranasal GRFT administration (7.5 or 15 mg/day) in pigs (n = 56). Pigs treated with 15 mg/day GRFT exhibited significantly reduced (p < 0.05) viremia 2, 4 and 7 days post-challenge, compared with untreated, challenged, and controls (log10 8.1 ± 0.2 vs. 9.0 ± 0.25, 8.2 ± 0.1 vs. 9.1 ± 0.2, and 8.9 ± 0.2 vs. 9.3 ± 0.2, respectively), along with earlier resolution of fever and a trend toward increased average daily gain over 42 days (p < 0.1). These findings are the first report of GRFT efficacy in pigs and support its potential as an antiviral strategy against PRRSV, alongside existing interventions.