Multi-targeting approach for nsp3, nsp9, nsp12 and nsp15 proteins of SARS-CoV-2 by Diosmin as illustrated by molecular docking and molecular dynamics simulation methodologies

Kumar, Sumit; Sharma, Prem Prakash; Upadhyay, Charu; Kempaiah, Prakasha; Rathi, Brijesh; Poonam, .

doi:10.1016/j.ymeth.2021.02.017

Cited by 16 publications

(11 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Molecular docking study of ivermectin, and remdesivir indicates spike, M, N, nsp14, and nsp16 as viable targets for drug treatment development of SARS-CoV-2 81 , 82 , while Raltegravir and Maraviroc are potential candidates to inhibit nsp-16 protein 83 . Multi-targeting features of Diosmin display highest binding affinity and inhibitory action of several non-structural proteins (nsp3, nsp9, nsp12, nsp15) 84 . This confirmation of the role of non-structural proteins in treatment validates our target proteins predictions.…”

Section: Discussionmentioning

confidence: 99%

The impact of the suppression of highly connected protein interactions on the corona virus infection

Torres

Kiwi

Schuller

2022

Sci Rep

View full text Add to dashboard Cite

Several highly effective Covid-19 vaccines are in emergency use, although more-infectious coronavirus strains, could delay the end of the pandemic even further. Because of this, it is highly desirable to develop fast antiviral drug treatments to accelerate the lasting immunity against the virus. From a theoretical perspective, computational approaches are useful tools for antiviral drug development based on the data analysis of gene expression, chemical structure, molecular pathway, and protein interaction mapping. This work studies the structural stability of virus–host interactome networks based on the graphical representation of virus–host protein interactions as vertices or nodes connected by commonly shared proteins. These graphical network visualization methods are analogous to those use in the design of artificial neural networks in neuromorphic computing. In standard protein-node-based network representation, virus–host interaction merges with virus–protein and host–protein networks, introducing redundant links associated with the internal virus and host networks. On the contrary, our approach provides a direct geometrical representation of viral infection structure and allows the effective and fast detection of the structural robustness of the virus–host network through proteins removal. This method was validated by applying it to H1N1 and HIV viruses, in which we were able to pinpoint the changes in the Interactome Network produced by known vaccines. The application of this method to the SARS-CoV-2 virus–host protein interactome implies that nonstructural proteins nsp4, nsp12, nsp16, the nuclear pore membrane glycoprotein NUP210, and ubiquitin specific peptidase USP54 play a crucial role in the viral infection, and their removal may provide an efficient therapy. This method may be extended to any new mutations or other viruses for which the Interactome Network is experimentally determined. Since time is of the essence, because of the impact of more-infectious strains on controlling the spread of the virus, this method may be a useful tool for novel antiviral therapies.

show abstract

Section: Discussionmentioning

confidence: 99%

The impact of the suppression of highly connected protein interactions on the corona virus infection

Torres

Kiwi

Schuller

2022

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The repurposing potential of 34 bioactive terpenes and their derivatives to Mpro and PLpro was also predicted by docking and MM/PBSA calculations . Other MM/PB(GB)SA-based drug repurposing works considering two or more targets include studies in the literature. − …”

Section: Methods and Approachesmentioning

confidence: 99%

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

Gao¹,

Wang²,

Chen³

et al. 2022

Chem. Rev.

View full text Add to dashboard Cite

Despite tremendous efforts in the past two years, our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), virus–host interactions, immune response, virulence, transmission, and evolution is still very limited. This limitation calls for further in-depth investigation. Computational studies have become an indispensable component in combating coronavirus disease 2019 (COVID-19) due to their low cost, their efficiency, and the fact that they are free from safety and ethical constraints. Additionally, the mechanism that governs the global evolution and transmission of SARS-CoV-2 cannot be revealed from individual experiments and was discovered by integrating genotyping of massive viral sequences, biophysical modeling of protein–protein interactions, deep mutational data, deep learning, and advanced mathematics. There exists a tsunami of literature on the molecular modeling, simulations, and predictions of SARS-CoV-2 and related developments of drugs, vaccines, antibodies, and diagnostics. To provide readers with a quick update about this literature, we present a comprehensive and systematic methodology-centered review. Aspects such as molecular biophysics, bioinformatics, cheminformatics, machine learning, and mathematics are discussed. This review will be beneficial to researchers who are looking for ways to contribute to SARS-CoV-2 studies and those who are interested in the status of the field.

show abstract

“…The nsp9 is single-strand RNA-binding protein of SARS-CoV (nsp9–SARS) which was found to be essential for viral replication ( Frieman et al, 2012 ). nsp9 of SARS-CoV-2 can bind to the nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain relating the viral replication and transcription ( Kumar M. et al, 2021 ), and it was also considered to be the therapy target for COVID-19 treatment ( Zhang et al, 2020 ; Kumar et al, 2021b ). There were several studies to screen the potential candidate compounds to bind or act on nsp9 by in silico tools ( Barros et al, 2020 ; Chandra et al, 2021 ; Junior et al, 2021 ), and one in vitro cellular assay showed the inhibition on nsp9 can reduce the viral replication of SARS-CoV-2 ( Littler et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…There were several studies to screen the potential candidate compounds to bind or act on nsp9 by in silico tools ( Barros et al, 2020 ; Chandra et al, 2021 ; Junior et al, 2021 ), and one in vitro cellular assay showed the inhibition on nsp9 can reduce the viral replication of SARS-CoV-2 ( Littler et al, 2021 ). The molecular docking results showed that curcumin can bind to the ligand binding site of nsp9, and curcumin can form about 11 interaction sites with nsp9 ( Kumar et al, 2021b ).…”

Section: Introductionmentioning

confidence: 99%

Pharmaceutical Prospects of Curcuminoids for the Remedy of COVID-19: Truth or Myth

Fu¹,

Kang³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is a positive-strand RNA virus, and has rapidly spread worldwide as a pandemic. The vaccines, repurposed drugs, and specific treatments have led to a surge of novel therapies and guidelines nowadays; however, the epidemic of COVID-19 is not yet fully combated and is still in a vital crisis. In repositioning drugs, natural products are gaining attention because of the large therapeutic window and potent antiviral, immunomodulatory, anti-inflammatory, and antioxidant properties. Of note, the predominant curcumoid extracted from turmeric (Curcuma longa L.) including phenolic curcumin influences multiple signaling pathways and has demonstrated to possess anti-inflammatory, antioxidant, antimicrobial, hypoglycemic, wound healing, chemopreventive, chemosensitizing, and radiosensitizing spectrums. In this review, all pieces of current information related to curcumin-used for the treatment and prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through in vitro, in vivo, and in silico studies, clinical trials, and new formulation designs are retrieved to re-evaluate the applications based on the pharmaceutical efficacy of clinical therapy and to provide deep insights into knowledge and strategy about the curcumin’s role as an immune booster, inflammatory modulator, and therapeutic agent against COVID-19. Moreover, this study will also afford a favorable application or approach with evidence based on the drug discovery and development, pharmacology, functional foods, and nutraceuticals for effectively fighting the COVID-19 pandemic.

show abstract

Multi-targeting approach for nsp3, nsp9, nsp12 and nsp15 proteins of SARS-CoV-2 by Diosmin as illustrated by molecular docking and molecular dynamics simulation methodologies

Cited by 16 publications

References 39 publications

The impact of the suppression of highly connected protein interactions on the corona virus infection

The impact of the suppression of highly connected protein interactions on the corona virus infection

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

Pharmaceutical Prospects of Curcuminoids for the Remedy of COVID-19: Truth or Myth

Contact Info

Product

Resources

About