PMID- 34678331 OWN - NLM STAT- MEDLINE DCOM- 20220225 LR - 20220225 IS - 1872-9096 (Electronic) IS - 0166-3542 (Linking) VI - 195 DP - 2021 Nov TI - Inhibition of endocytosis of porcine reproductive and respiratory syndrome virus by rottlerin and its potential prophylactic administration in piglets. PG - 105191 LID - S0166-3542(21)00181-9 [pii] LID - 10.1016/j.antiviral.2021.105191 [doi] AB - Owing to several limitations of porcine reproductive and respiratory syndrome virus (PRRSV) control procedures, the importance of antiviral agents is increasing; however, limited studies have been done on the development of anti-PRRSV agents. Herein, we explored the antiviral effect and mechanism of rottlerin against PRRSV. We demonstrated that treatment of rottlerin at an early stage of PRRSV infection significantly inhibited the viral replication. PRRSV infection induced protein kinase C-delta phosphorylation, which was specifically downregulated by rottlerin. The treatment of rottlerin led to disrupting the PRRSV entry pathway by blocking endocytosis of the virions. Further, to evaluate the anti-PRRSV effect of the rottlerin in vivo, we administrated rottlerin loaded liposome to pigs infected with PRRSV LMY or FL12 strain. The treatment of rottlerin-liposome reduced the blood viral load, interstitial pneumonia and clinical scores compared to untreated pigs. These results provide an evidence of anti-PRRSV effect of rottlerin in vitro via inhibiting PRRSV internalization and in vivo, all of which strongly suggest the applicability of rottlerin as a potential PRRSV prophylactic treatment. CI - Copyright (c) 2021. Published by Elsevier B.V. FAU - Kang, Yeong-Lim AU - Kang YL AD - Laboratory of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Seoul, 05029, Republic of Korea. FAU - Oh, Changin AU - Oh C AD - Department of Genetics, Yale University School of Medicine, New Haven, CT, 06520-8005, USA. FAU - Ahn, So-Hyun AU - Ahn SH AD - Laboratory of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Seoul, 05029, Republic of Korea. FAU - Choi, Jong-Chul AU - Choi JC AD - Laboratory of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Seoul, 05029, Republic of Korea. FAU - Choi, Hwi-Yeon AU - Choi HY AD - Laboratory of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Seoul, 05029, Republic of Korea. FAU - Lee, Sang-Won AU - Lee SW AD - Laboratory of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Seoul, 05029, Republic of Korea. FAU - Choi, In-Soo AU - Choi IS AD - Laboratory of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Seoul, 05029, Republic of Korea. FAU - Song, Chang-Seon AU - Song CS AD - Laboratory of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Seoul, 05029, Republic of Korea. FAU - Lee, Joong-Bok AU - Lee JB AD - Laboratory of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Seoul, 05029, Republic of Korea. FAU - Park, Seung-Yong AU - Park SY AD - Laboratory of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Seoul, 05029, Republic of Korea. Electronic address: paseyo@konkuk.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211020 PL - Netherlands TA - Antiviral Res JT - Antiviral research JID - 8109699 RN - 0 (Acetophenones) RN - 0 (Antiviral Agents) RN - 0 (Benzopyrans) RN - E29LP3ZMUH (rottlerin) SB - IM MH - Acetophenones/*pharmacology MH - Animals MH - Antiviral Agents/*pharmacology MH - Benzopyrans/*pharmacology MH - Cell Line MH - Endocytosis/*drug effects MH - Lung Diseases, Interstitial/prevention & control MH - Porcine Reproductive and Respiratory Syndrome/*drug therapy/pathology MH - Porcine respiratory and reproductive syndrome virus/*drug effects MH - Swine MH - Viral Load/drug effects MH - Virus Internalization/drug effects MH - Virus Replication/drug effects OTO - NOTNLM OT - Antivirals OT - Liposome OT - PRRSV OT - Protein kinase C OT - Rottlerin EDAT- 2021/10/23 06:00 MHDA- 2022/02/26 06:00 CRDT- 2021/10/22 20:31 PHST- 2021/05/15 00:00 [received] PHST- 2021/08/27 00:00 [revised] PHST- 2021/10/18 00:00 [accepted] PHST- 2021/10/23 06:00 [pubmed] PHST- 2022/02/26 06:00 [medline] PHST- 2021/10/22 20:31 [entrez] AID - S0166-3542(21)00181-9 [pii] AID - 10.1016/j.antiviral.2021.105191 [doi] PST - ppublish SO - Antiviral Res. 2021 Nov;195:105191. doi: 10.1016/j.antiviral.2021.105191. Epub 2021 Oct 20.