Computational insights into RNAi-based therapeutics for foot and mouth disease of Bostaurus

Tanmaya Kumar Sahu,Anoop Kishor Singh Gurjar,Prabina Kumar Meher,Suresh H Basagoudanavar,Aniket Sanyal,Atmakuri Ramakrishna Rao,Cini Varghese,Govind Pratap Rao,Anil Rai,Neha Guleria,Sudeep Marwaha

doi:10.1038/s41598-020-78541-6

Abstract

Foot-and-mouth disease (FMD) endangers a large number of livestock populations across the globe being a highly contagious viral infection in wild and domestic cloven-hoofed animals. It adversely affects the socioeconomic status of millions of households. Vaccination has been used to protect animals against FMD virus (FMDV) to some extent but the effectiveness of available vaccines has been decreased due to high genetic variability in the FMDV genome. Another key aspect that the current vaccines are not favored is they do not provide the ability to differentiate between infected and vaccinated animals. Thus, RNA interference (RNAi) being a potential strategy to control virus replication, has opened up a new avenue for controlling the viral transmission. Hence, an attempt has been made here to establish the role of RNAi in therapeutic developments for FMD by computationally identifying (i) microRNA (miRNA) targets in FMDV using target prediction algorithms, (ii) targetable genomic regions in FMDV based on their dissimilarity with the host genome and, (iii) plausible anti-FMDV miRNA-like simulated nucleotide sequences (SNSs). The results revealed 12 mature host miRNAs that have 284 targets in 98 distinct FMDV genomic sequences. Wet-lab validation for anti-FMDV properties of 8 host miRNAs was carried out and all were observed to confer variable magnitude of antiviral effect. In addition, 14 miRBase miRNAs were found with better target accessibility in FMDV than that of Bostaurus. Further, 8 putative targetable regions having sense strand properties of siRNAs were identified on FMDV genes that are highly dissimilar with the host genome. A total of 16 SNSs having > 90% identity with mature miRNAs were also identified that have targets in FMDV genes. The information generated from this study is populated at http://bioinformatics.iasri.res.in/fmdisc/ to cater the needs of biologists, veterinarians and animal scientists working on FMD.

Highlights

Foot-and-mouth disease (FMD) endangers a large number of livestock populations across the globe being a highly contagious viral infection in wild and domestic cloven-hoofed animals
RNA interference (RNAi) based therapeutics present a new strategy for inhibiting the replication of certain viruses[2]
In silico approaches were explored in this study to understand applicability of RNAi based therapeutic solutions for FMD

Summary

Introduction

Foot-and-mouth disease (FMD) endangers a large number of livestock populations across the globe being a highly contagious viral infection in wild and domestic cloven-hoofed animals. De los Santos et al.[4] have demonstrated a significant reduction in the virus yield with a reduced viral RNA and protein synthesis as compared to the control cells by expressing an shRNA specific to 2B nonstructural protein coding region of FMDV RNA in porcine cells during the infection. They have reported that their strategy is effective against multiple FMDV serotypes. A database was populated with the integrated information obtained from the study

Methods

Results

Conclusion