Simian Virus 40 Large T Antigen as a Model to Test the Efficacy of Flouroquinolones against Viral Helicases

Siddiqui, Sammer; Anwar, Muhammad Sabieh; Naeem, Sadaf; Abidi, Syed Hani; Zarina, Shamshad; Ali, Sajid

doi:10.6026/97320630014075

Cited by 3 publications

(1 citation statement)

References 13 publications

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“…Fluoroquinolones such as enoxacin are broad-spectrum synthetic antibiotics used in different clinical conditions like urinary tract-, respiratory-, and systemic infections 19,20 . Although quinolones are known to typically inhibit DNA replication by targeting bacterial DNA gyrases 21 , a growing body of evidence has revealed that some members of this family of antibiotics could also inhibit viral helicases, attenuate cytokine production and pro-in ammatory reactions 22 , and more importantly enhance the RNAi process as an in ammation-free innate immune defense against viral infections 23 .…”

Section: Introductionmentioning

confidence: 99%

In silico analysis suggests the RNAi-enhancing antibiotic enoxacin as a potential inhibitor of SARS-CoV-2 infection

Ahmadi

Moradi

2020

Preprint

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COVID-19 has currently become the biggest challenge in the world. There is still no specific medicine for COVID-19, which leaves a critical gap for the identification of new drug candidates for the disease. Recent studies have reported that the small-molecule enoxacin exerts an antiviral activity by enhancing the RNAi pathway. The aim of this study is to analyze if enoxacin can exert anti-SARS-CoV-2 effects. We exploit multiple computational tools and databases to examine (i) whether the RNAi mechanism, as the target pathway of enoxacin, could act on the SARS-CoV-2 genome, and (ii) microRNAs induced by enoxacin might directly silence viral components as well as the host cell proteins mediating the viral entry and replication. We find that the RNA genome of SARS-CoV-2 is a suitable substrate for DICER activity. We also highlight several enoxacin-enhanced microRNAs which could target SARS-CoV-2 components, pro-inflammatory cytokines, host cell components facilitating viral replication, and transcription factors enriched in lung stem cells, thereby promoting their differentiation and lung regeneration. Finally, our analyses identify several enoxacin-targeted regulatory modules that were critically associated with exacerbation of the SARS-CoV-2 infection. Overall, our analysis suggests that enoxacin could be a promising candidate for COVID-19 treatment through enhancing the RNAi pathway.

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Section: Introductionmentioning

confidence: 99%

In silico analysis suggests the RNAi-enhancing antibiotic enoxacin as a potential inhibitor of SARS-CoV-2 infection

Ahmadi

Moradi

2020

Preprint

View full text Add to dashboard Cite

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In silico analysis suggests the RNAi-enhancing antibiotic enoxacin as a potential inhibitor of SARS-CoV-2 infection

Ahmadi

Moradi

2021

Sci Rep

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COVID-19 has currently become the biggest challenge in the world. There is still no specific medicine for COVID-19, which leaves a critical gap for the identification of new drug candidates for the disease. Recent studies have reported that the small-molecule enoxacin exerts an antiviral activity by enhancing the RNAi pathway. The aim of this study is to analyze if enoxacin can exert anti-SARS-CoV-2 effects. We exploit multiple computational tools and databases to examine (i) whether the RNAi mechanism, as the target pathway of enoxacin, could act on the SARS-CoV-2 genome, and (ii) microRNAs induced by enoxacin might directly silence viral components as well as the host cell proteins mediating the viral entry and replication. We find that the RNA genome of SARS-CoV-2 might be a suitable substrate for DICER activity. We also highlight several enoxacin-enhanced microRNAs which could target SARS-CoV-2 components, pro-inflammatory cytokines, host cell components facilitating viral replication, and transcription factors enriched in lung stem cells, thereby promoting their differentiation and lung regeneration. Finally, our analyses identify several enoxacin-targeted regulatory modules that were critically associated with exacerbation of the SARS-CoV-2 infection. Overall, our analysis suggests that enoxacin could be a promising candidate for COVID-19 treatment through enhancing the RNAi pathway.

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Identification of Novel Phyto-chemicals from Ocimum basilicum for the Treatment of Parkinson’s Disease using In Silico Approach

Mubashir

Fatima

Naeem

2020

CAD

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: Parkinson’s disease is characterized by decrease level of dopaminergic neurotransmitters and this decrease is due to degradation of dopamine by protein human Monoamine Oxidase B (MAO-B). Thus, in order to treat Parkinson’s disease MAO-B should be inhibited. During this study, an attempt is made to find the novel phytochemicals from plant Ocimum bacillicum that can inhibit this protein. The data of chemical constituents from plant Ocimum bacillicum was collected and inhibitory activity of these phytochemicals were then predicted by using in-silico methods, both Structure Based (SB) and Ligand Based Virtual Screening. Molecular docking, one of the common Structure Based Virtual Screening method, have been used during this search. Traditionally, molecular docking is used to predict the orientation and binding affinity of the ligand within the active site of protein. Molegro virtual docker (MVD) software has been used for this purpose. On the other hand, Random Forest Model, one of the LBVS method, also been used to predict the activity of all of the chemical constituents of Ocimum bacillicum. : During the docking studies, All the 108 compounds found in Ocimum bacillicum were docked with in the active site of MAO-B (PDB code: 4A79) out of which 57 compounds successfully formed the hydrogen bond with the tyr 435, a crucial amino acid for the biology activity of the enzyme. Rutin (-182.976 Kcal/mol), Luteolin (-163.171 Kcal/mol), Eriodictylol-7-O-glucoside (-160.13 Kcal/mol), Rosmaranic Acid (-133.484 Kcal/mol) and Isoquercitrin (-131.493 Kcal/mol) are among the top hits with the highest MolDock score along with hydrogen interaction with tyr 435. : Using the RF model, ten compounds out of 108 chemical constituent of Ocimum bacillicum were predicted to be active, Apigenin (1.0), Eriodictyol (1.0), Orientin (0.876), Kaempferol (0.8536), Luteolin (0.813953), Rosmarinic-Acid (0.7738095) are predicted to be most active with highest RF score. : The comparison of the two screening methods shows that the ten compounds that were predicted to be active by RF model, are also found in top hits of docking studies with highest score. The top hits obtained during this study are predicted to be the inhibitor of MAO-B, thus, could be used further for the development of drugs for the treatment Parkinson’s disease (PD).

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Simian Virus 40 Large T Antigen as a Model to Test the Efficacy of Flouroquinolones against Viral Helicases

Cited by 3 publications

References 13 publications

In silico analysis suggests the RNAi-enhancing antibiotic enoxacin as a potential inhibitor of SARS-CoV-2 infection

In silico analysis suggests the RNAi-enhancing antibiotic enoxacin as a potential inhibitor of SARS-CoV-2 infection

In silico analysis suggests the RNAi-enhancing antibiotic enoxacin as a potential inhibitor of SARS-CoV-2 infection

Identification of Novel Phyto-chemicals from Ocimum basilicum for the Treatment of Parkinson’s Disease using In Silico Approach

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