Arbidol HCl Inhibits PRRSV Infection by Downregulating CD163 and MYH9 Expression and Modulating Inflammatory Responses

Porcine reproductive and respiratory syndrome (PRRS) constitutes a major challenge for global pig production, yet effective therapeutic interventions remain elusive. Our study investigated the antiviral potency of Arbidol HCl in counteracting PRRSV infection through comprehensive in permissive cells and in vivo approaches. Our observations demonstrate that Arbidol HCl confers an obvious antiviral activity against varied PRRSV isolates in MARC-145 cells and primary porcine alveolar macrophages (PAMs). Mechanistic studies revealed that Arbidol HCl inhibits the early stages of PRRSV infection by significantly downregulating the expression of key viral receptors cysteine-rich scavenger receptor (CD163) and myosin heavy chain 9 (MYH9), thereby disrupting viral attachment and internalization. Subsequent validation studies indicated that Arbidol HCl attenuates proinflammatory responses caused by PRRSV via suppressing the toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway. In vivo experiments using PRRSV-infected piglets demonstrated that Arbidol HCl treatment significantly reduced viral loads in serum, alleviated lung pathological damage, and mitigated systemic inflammatory responses. These results collectively establish Arbidol HCl as a promising dual-action therapeutic agent that combines direct antiviral effects with anti-inflammatory properties. Our study offers hope for developing a practical therapeutic intervention that could significantly impact swine health and food security worldwide. It will provide a novel approach for PRRS prevention and treatment in swine production.