Viruses 2022, 14, 2666. https://doi.org/10.3390/v14122666 www.mdpi.com/journal/viruses Article Effect of BIO‐PLY TM , a Platelet‐Rich Plasma Derived Biologic on PRRSV‐2‐infected macrophages Alba Frias‐De‐Diego 1 , Jessica M. Gilbertie 2 , Frank Scholle 3 , Sarah Dejarnette 3 and Elisa Crisci 1, * 1 Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA 2 Department of Biomedical Affairs and Research, Edward Via College of Osteopathic Medicine, Blacksburg, VA 24060, USA 3 Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695, USA * Correspondence: ecrisci@ncsu.edu; Tel.: +1‐919‐513‐6255 Abstract: Porcine Reproductive and Respiratory Syndrome (PRRS) is the one of the most devastat‐ ing diseases impacting the swine industry worldwide. Control and prevention methods rely on bi‐ osafety measures and vaccination. As an RNA virus with a high rate of mutation, vaccines are only partially effective against circulating and newly emerging strains. To reduce the burden of this dis‐ ease, research on alternative control methods is needed. Here, we assess the in vitro antiviral effect of a novel platelet‐rich plasma‐derived biologic termed BIO‐PLY TM (for the BIOactive fraction of Platelet‐rich plasma LYsate) from both swine and equine origin. Our results show that BIO‐PLY TM significantly reduces the amount of PRRSV viral load determined by RT‐qPCR and the number of infectious viral particles measured by TCID50 in infected porcine alveolar and parenchymal macro‐ phages. This study also showed limited toxicity of BIO‐PLY TM in vitro and aspects of its immuno‐ modulatory capacity evaluating the regulation of reactive oxygen species and cytokines production in infected cells. Finally, this study presents promising data on the effect of BIO‐PLY TM on other RNA viruses such as human A influenza viruses and coronavirus. Keywords: antivirals; biologic; porcine macrophages; PRRSV 1. Introduction In 2019, international commerce of livestock and swine products surpassed USD 20 billion worldwide, and over USD 7 billion in the U.S. alone as reported by the United States Department of Agriculture (USDA) [1]. Porcine Reproductive and Respiratory Syn‐ drome virus (PRRSV) is one of the most prominent diseases worldwide in the swine in‐ dustry, causing over USD 600 million in losses every year in the U.S. [2,3]. PRRSV is an enveloped positive single stranded RNA virus with tropism for the cells from the mono‐ cytic lineage, particularly macrophages that are known to be the virus target cell [4]. PRRSV is divided into two species: PRRSV‐1, mainly present in Asia and Europe, and PRRSV‐2, with higher prevalence in the U.S. [4]. As many other RNA viruses, PRRSV displays a high mutation rate and ability to adapt and spread rapidly within and between herds [5,6]. The current control and prevention measures for PRRSV infection are based on biosafety protocols and immunization [7]. However, given the nature of the virus and its high mutation rate [5], approximately 20%–30% of US breeding herds still become in‐ fected with PRRSV every year, since vaccines cannot yet achieve complete cross protec‐ tion to circulating and newly emerging strains [8]. For that reason, research on alternative treatments that could lead to a reduction of the burden of this disease are of interest. Some approaches that have proven their effectiveness against PRRSV in vitro are plant extracts like Caesalpinia sappan [9]d, tea polyphenols [10], nanoparticles [11], carbon‐based materi‐ als [12] or mycotoxins [13] among others. However, a number of these options, such as Citation: Frias‐De‐Diego, A.; Gilbertie, J.M.; Scholle, F.; Dejarnette, S.; Crisci, E. Effect of BIO‐PLY TM , a Platelet‐Rich Plasma Derived Biologic on PRRSV‐2‐infected macrophages. Viruses 2022, 14, 2666. https://doi.org/10.3390/v14122666 Academic Editor: Tongling Shan Received: 27 October 2022 Accepted: 23 November 2022 Published: 28 November 2022 Publisher’s Note: MDPI stays neu‐ tral with regard to jurisdictional claims in published maps and institu‐ tional affiliations. Copyright: © 2022 by the authors. Li‐ censee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and con‐ ditions of the Creative Commons At‐ tribution (CC BY) license (https://cre‐ ativecommons.org/licenses/by/4.0/).