In-vitro inhibition of spring viremia of carp virus replication by RNA interference targeting the RNA-dependent RNA polymerase gene

Fouad, Alamira Marzouk; Soliman, Hatem; Abdallah, Ebtsam Sayed Hassan; Ibrahim, Sherif; El-Matbouli, Mansour; Elkamel, Ahmad A.

doi:10.1016/j.jviromet.2018.10.008

Cited by 12 publications

(8 citation statements)

References 38 publications

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“…Upon entry inside the host cell, viral RdRp enables multiplication of the +ssRNA virus (Fouad, Soliman et al 2019) and eventually the consequences of the viral infection in the host (Kirchdoerfer and Ward 2019). Thus, RdRp has always been a favorite drug target in antiviral therapeutic research (Tchesnokov, Feng et al 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Upon intracellular uptake beclabuvir allosterically binds to the noncatalytic Thumb 1 site (Figure 4) of viral RdRp which slowdown the RNA synthesis process (Garimella, Tao et al 2018). However, in the case of SARS-CoV-2 beclabuvir occupies the active site environment (ASE), ( Figure 5) of the RdRp which is essential for the RNA-dependent polymerase activity (Fouad, Soliman et al 2019) ). The major interacting residues were I591, Y621, C624, D625, A690, N693, L760, D762, D763…”

Section: Discussionmentioning

confidence: 99%

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Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2)

Dutta¹,

Shityakov²,

Морозова³

et al. 2020

Preprint

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Recent emergence of novel coronavirus (SARS-CoV-2) in Wuhan, China has resulted more than 14,510 global deaths. To date well-established therapeutics modules for infected patients are unknown. In this present initiative, molecular interactions between well-known antiviral drugs against the Hepatitis-C virus (HCV) have been investigated theoretically against the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. HCV and SARS-CoV-2 are both +ssRNA viruses. At 25o C beclabuvir, a non-nucleoside inhibitor of the RdRp of the HCV can efficiently bind to RdRp of the SARS-CoV-2 (ΔGAutoDock = -9.95 kcal mol-1) with an inhibition constant of only 51.03 nM. Both the ΔGLondon and ΔGGBVI / WSA values were - 9.06 and - 6.67 kcal mol-1, respectively for SARS-CoV-2. In addition, beclabuvir also shows better binding free energy (ΔGvina = 9.7 kcal mol-1) than that of the Thumb 1 domain of RdRp of HCV (ΔGvina = 7.7 kcal mol-1). InterProScan has suggested the RNA-directed 5'-3' polymerase activity existed within 549 to 776 amino acid residues of RdRp. Moreover, major interacting amino acid residues were I591, Y621, C624, D625, A690, N693, L760, D762, D763 and E813-N817. Molecular interaction suggests occupancy of beclabuvir inside the active site environment of the RdRp which is essential for viral RNA synthesis. In conclusion, results suggest beclabuvir has high therapeutic potential as an anti-SARS-CoV-2 drug.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2)

Dutta¹,

Shityakov²,

Морозова³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Upon entry inside the host cell, viral RdRp enables multiplication of the +ssRNA virus [18,19] and eventually the consequences of the viral infection in the host [17].…”

Section: Discussionmentioning

confidence: 99%

“…Upon intracellular uptake beclabuvir allosterically binds to the non-catalytic Thumb 1 site (Figure 4) of viral RdRp which slowdown the RNA synthesis process [25]. However, in the case of RdRpSARS-CoV-2 beclabuvir occupies the active site environment (ASE), ( Figure 5) is essential for the RNA-dependent polymerase activity [18,19] ). The major interacting residues were I591, Y621, C624, D625, A690, N693, L760, D762, D763 and E813-N817 (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2)

Dutta¹,

Shityakov²,

Морозова³

et al. 2020

Preprint

View full text Add to dashboard Cite

Recent emergence of novel coronavirus (SARS-CoV-2) all over the world has resulted more than 33,106 global deaths. To date well-established therapeutics modules for infected patients are unknown. In this present initiative, molecular interactions between FDA-approved antiviral drugs against the Hepatitis-C virus (HCV) have been investigated theoretically against the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. HCV and SARS-CoV-2 are both +ssRNA viruses. At 25o C beclabuvir, a non-nucleoside inhibitor of the RdRpHCV can efficiently bind to RdRp SARS-CoV-2 (ΔGAutoDock = -9.95 kcal mol-1) with an inhibition constant of 51.03 nM. Both the ΔGLondon and ΔGGBVI / WSA values were - 9.06 and - 6.67 kcal mol-1, respectively for binding of beclabuvir to RdRpSARS-CoV-2. In addition, beclabuvir has also shown better binding free energy with RdRpSARS-CoV-2 (ΔGvina = -8.0 kcal mol-1) than that observed with the Thumb 1 domain of RdRpHCV (ΔGvina = -7.1 kcal mol-1). InterProScan has suggested the RNA-directed 5'-3' polymerase activity exists within 549th to 776th amino acid residues of RdRpSARS-CoV, where the major amino acid residues interacting being I591, Y621, C624, D625, A690, N693, L760, D762, D763, and E813-N817. Molecular interaction suggests occupancy of beclabuvir inside the active site environment of the RdRpSARS-CoV-2, the enzyme essential for viral RNA synthesis. In conclusion, results suggest beclabuvir may serve as an anti-SARS-CoV-2 drug.

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“…RNAi is a gene silencing mechanism at the post-transcriptional level with high specificity and can inhibit gene expression with high efficiency. Therefore, RNAi has been considered as an effective strategy to protect against bacterial and viral pathogens [22,23]. RNAi is triggered by endogenous or exogenous 21-23 nt RNA duplexes [17], and shRNA and siRNA are two commonly used RNA molecules to block gene expression [17,24].…”

Section: Discussionmentioning

confidence: 99%

Short hairpin RNAs targeting M and N genes reduce replication of porcine deltacoronavirus in ST cells

Liu

et al. 2019

Virus Genes

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Porcine deltacoronavirus (PDCoV) is a recently identified coronavirus that causes intestinal diseases in neonatal piglets with diarrhea, vomiting, dehydration, and post-infection mortality of 50-100%. Currently, there are no effective treatments or vaccines available to control PDCoV. To study the potential of RNA interference (RNAi) as a strategy against PDCoV infection, two short hairpin RNA (shRNA)-expressing plasmids (pGenesil-M and pGenesil-N) that targeted the M and N genes of PDCoV were constructed and transfected separately into swine testicular (ST) cells, which were then infected with PDCoV strain HB-BD. The potential of the plasmids to inhibit PDCoV replication was evaluated by cytopathic effect, virus titers, and real-time quantitative RT-PCR assay. The cytopathogenicity assays demonstrated that pGenesil-M and pGenesil-N protected ST cells against pathological changes with high specificity and efficacy. The 50% tissue culture infective dose showed that the PDCoV titers in ST cells treated with pGenesil-M and pGenesil-N were reduced 13.2-and 32.4-fold, respectively. Real-time quantitative RT-PCR also confirmed that the amount of viral RNA in cell cultures pre-transfected with pGenesil-M and pGenesil-N was reduced by 45.8 and 56.1%, respectively. This is believed to be the first report to show that shRNAs targeting the M and N genes of PDCoV exert antiviral effects in vitro, which suggests that RNAi is a promising new strategy against PDCoV infection.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

show abstract

In-vitro inhibition of spring viremia of carp virus replication by RNA interference targeting the RNA-dependent RNA polymerase gene

Cited by 12 publications

References 38 publications

Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2)

Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2)

Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2)

Short hairpin RNAs targeting M and N genes reduce replication of porcine deltacoronavirus in ST cells

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