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

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...

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Autores principales: Tanmaya Kumar Sahu, Anoop Kishor Singh Gurjar, Prabina Kumar Meher, Cini Varghese, Sudeep Marwaha, Govind Pratap Rao, Anil Rai, Neha Guleria, Suresh H. Basagoudanavar, Aniket Sanyal, Atmakuri Ramakrishna Rao
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Publicado: Nature Portfolio 2020
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spelling oai:doaj.org-article:24dd9c8ebb6b46a9a1d73337e8af597a2021-12-02T12:33:05ZComputational insights into RNAi-based therapeutics for foot and mouth disease of Bos taurus10.1038/s41598-020-78541-62045-2322https://doaj.org/article/24dd9c8ebb6b46a9a1d73337e8af597a2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78541-6https://doaj.org/toc/2045-2322Abstract 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 Bos taurus. 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.Tanmaya Kumar SahuAnoop Kishor Singh GurjarPrabina Kumar MeherCini VargheseSudeep MarwahaGovind Pratap RaoAnil RaiNeha GuleriaSuresh H. BasagoudanavarAniket SanyalAtmakuri Ramakrishna RaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Tanmaya Kumar Sahu
Anoop Kishor Singh Gurjar
Prabina Kumar Meher
Cini Varghese
Sudeep Marwaha
Govind Pratap Rao
Anil Rai
Neha Guleria
Suresh H. Basagoudanavar
Aniket Sanyal
Atmakuri Ramakrishna Rao
Computational insights into RNAi-based therapeutics for foot and mouth disease of Bos taurus
description 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 Bos taurus. 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.
format article
author Tanmaya Kumar Sahu
Anoop Kishor Singh Gurjar
Prabina Kumar Meher
Cini Varghese
Sudeep Marwaha
Govind Pratap Rao
Anil Rai
Neha Guleria
Suresh H. Basagoudanavar
Aniket Sanyal
Atmakuri Ramakrishna Rao
author_facet Tanmaya Kumar Sahu
Anoop Kishor Singh Gurjar
Prabina Kumar Meher
Cini Varghese
Sudeep Marwaha
Govind Pratap Rao
Anil Rai
Neha Guleria
Suresh H. Basagoudanavar
Aniket Sanyal
Atmakuri Ramakrishna Rao
author_sort Tanmaya Kumar Sahu
title Computational insights into RNAi-based therapeutics for foot and mouth disease of Bos taurus
title_short Computational insights into RNAi-based therapeutics for foot and mouth disease of Bos taurus
title_full Computational insights into RNAi-based therapeutics for foot and mouth disease of Bos taurus
title_fullStr Computational insights into RNAi-based therapeutics for foot and mouth disease of Bos taurus
title_full_unstemmed Computational insights into RNAi-based therapeutics for foot and mouth disease of Bos taurus
title_sort computational insights into rnai-based therapeutics for foot and mouth disease of bos taurus
publisher Nature Portfolio
publishDate 2020
url https://doaj.org/article/24dd9c8ebb6b46a9a1d73337e8af597a
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