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Kinetics and synergistic effects of siRNAs targeting structural and replicase genes of SARS-associated coronavirus.

ABSTRACT: SARS-associated coronavirus was identified as the etiological agent of severe acute respiratory syndrome and a large virus pool was identified in wild animals. Virus generates drug resistance through fast mutagenesis and escapes antiviral treatment. siRNAs targeting different genes would be an alternative for overcoming drug resistance. Here, we report effective siRNAs targeting structural genes (i.e., spike, envelope, membrane, and nucleocapsid) and their antiviral kinetics. We also showed the synergistic effects of two siRNAs targeting different functional genes at a very low dose. Our findings may pave a way to develop cost effective siRNA agents for antiviral therapy in the future.

SUBMITTER: He ML

PROVIDER: S-EPMC7094648 | biostudies-literature | 2006 May

REPOSITORIES: biostudies-literature

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Kinetics and synergistic effects of siRNAs targeting structural and replicase genes of SARS-associated coronavirus.

He Ming-Liang ML He Ming-Liang ML Zheng Bo-jian BJ Chen Ying Y Wong Kin-Ling KL Huang Jian-Dong JD Lin Marie C MC Peng Ying Y Yuen Kwok Y KY Sung Joseph J Y JJ Kung Hsiang-fu HF

FEBS letters 20060330 10

SARS-associated coronavirus was identified as the etiological agent of severe acute respiratory syndrome and a large virus pool was identified in wild animals. Virus generates drug resistance through fast mutagenesis and escapes antiviral treatment. siRNAs targeting different genes would be an alternative for overcoming drug resistance. Here, we report effective siRNAs targeting structural genes (i.e., spike, envelope, membrane, and nucleocapsid) and their antiviral kinetics. We also showed the ...[more]

PMID: 16638566

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Project description:SARS-CoV-2 is a highly transmissible and pathogenic coronavirus that first emerged in late 2019 and has since triggered a pandemic of acute respiratory disease named COVID-19 which poses a significant threat to all public health institutions in the absence of specific antiviral treatment. Since the outbreak began in March 2020, India has reported 4.77 lakh Coronavirus deaths, according to the World Health Organization (WHO). The innate RNA interference (RNAi) pathway, on the other hand, allows for the development of nucleic acid-based antiviral drugs in which complementary small interfering RNAs (siRNAs) mediate the post-transcriptional gene silencing (PTGS) of target mRNA. Therefore, in this current study, the potential of RNAi was harnessed to construct siRNA molecules that target the consensus regions of specific structural proteins associated genes of SARS-CoV-2, such as the envelope protein gene (E), membrane protein gene (M), nucleocapsid phosphoprotein gene (N), and surface glycoprotein gene (S) which are important for the viral pathogenesis. Conserved sequences of 811 SARS-CoV-2 strains from around India were collected to design 21 nucleotides long siRNA duplex based on various computational algorithms and parameters targeting E, M, N and S genes. The proposed siRNA molecules possessed sufficient nucleotide-based and other features for effective gene silencing and BLAST results revealed that siRNAs' targets have no significant matches across the whole human genome. Hence, siRNAs were found to have no off-target effects on the genome, ruling out the possibility of off-target silencing. Finally, out of 157 computationally identified siRNAs, only 4 effective siRNA molecules were selected for each target gene which is proposed to exert the best action based on GC content, free energy of folding, free energy of binding, melting temperature, heat capacity and molecular docking analysis with Human AGO2 protein. Our engineered siRNA candidates could be used as a genome-level therapeutic treatment against various sequenced SARS-CoV-2 strains in India. However, future applications will necessitate additional validations in vitro and in vivo animal models.

Dataset Information

Kinetics and synergistic effects of siRNAs targeting structural and replicase genes of SARS-associated coronavirus.

Publications

Kinetics and synergistic effects of siRNAs targeting structural and replicase genes of SARS-associated coronavirus.

Similar Datasets

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