Computational Study on Potential Novel Anti-Ebola Virus Protein VP35 Natural Compounds

Darko, Louis K. S.; Broni, Emmanuel; Amuzu, Dominic S. Y.; Wilson, Michael D.; Parry, Christian S.; Kwofie, Samuel K.

doi:10.3390/biomedicines9121796

Cited by 15 publications

(8 citation statements)

References 135 publications

(170 reference statements)

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“…Therefore, this study employed similar techniques to identify potential anti-EBOV VP40 lead compounds from natural product sources and to repurpose currently approved drugs. This study bolsters the findings of existing studies undertaken to find potential EBOV inhibitors to increase our therapeutic arsenal against EVD [ 94 , 237 , 256 , 257 , 258 ]. A total of 32,300 ligands were successfully screened against VP40, of which 65 (42 natural products and 23 approved drugs) were predicted to be potential anti-EBOV compounds.…”

Section: Discussionsupporting

confidence: 74%

Cheminformatics-Based Study Identifies Potential Ebola VP40 Inhibitors

Broni

Ashley

Adams

et al. 2023

IJMS

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The Ebola virus (EBOV) is still highly infectious and causes severe hemorrhagic fevers in primates. However, there are no regulatorily approved drugs against the Ebola virus disease (EVD). The highly virulent and lethal nature of EVD highlights the need to develop therapeutic agents. Viral protein 40 kDa (VP40), the most abundantly expressed protein during infection, coordinates the assembly, budding, and release of viral particles into the host cell. It also regulates viral transcription and RNA replication. This study sought to identify small molecules that could potentially inhibit the VP40 protein by targeting the N-terminal domain using an in silico approach. The statistical quality of AutoDock Vina’s capacity to discriminate between inhibitors and decoys was determined, and an area under the curve of the receiver operating characteristic (AUC-ROC) curve of 0.791 was obtained. A total of 29,519 natural-product-derived compounds from Chinese and African sources as well as 2738 approved drugs were successfully screened against VP40. Using a threshold of −8 kcal/mol, a total of 7, 11, 163, and 30 compounds from the AfroDb, Northern African Natural Products Database (NANPDB), traditional Chinese medicine (TCM), and approved drugs libraries, respectively, were obtained after molecular docking. A biological activity prediction of the lead compounds suggested their potential antiviral properties. In addition, random-forest- and support-vector-machine-based algorithms predicted the compounds to be anti-Ebola with IC50 values in the micromolar range (less than 25 μM). A total of 42 natural-product-derived compounds were identified as potential EBOV inhibitors with desirable ADMET profiles, comprising 1, 2, and 39 compounds from NANPDB (2-hydroxyseneganolide), AfroDb (ZINC000034518176 and ZINC000095485942), and TCM, respectively. A total of 23 approved drugs, including doramectin, glecaprevir, velpatasvir, ledipasvir, avermectin B1, nafarelin acetate, danoprevir, eltrombopag, lanatoside C, and glycyrrhizin, among others, were also predicted to have potential anti-EBOV activity and can be further explored so that they may be repurposed for EVD treatment. Molecular dynamics simulations coupled with molecular mechanics Poisson–Boltzmann surface area calculations corroborated the stability and good binding affinities of the complexes (−46.97 to −118.9 kJ/mol). The potential lead compounds may have the potential to be developed as anti-EBOV drugs after experimental testing.

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Section: Discussionsupporting

confidence: 74%

Cheminformatics-Based Study Identifies Potential Ebola VP40 Inhibitors

Broni

Ashley

Adams

et al. 2023

IJMS

Self Cite

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“…Huperzine A, for example, has been proven to be anti-Alzheimer's disease, and the study was based on MDS. Moreover, MDS has also been found to have great potential in the treatment of Ebola virus (EBOV) (Darko et al, 2021). As in our study using MDS, DPGS analogs were also able to block interleukin-6 (IL-6) and influence the course of inflammatory diseases (Sanader Maršić et al, 2021).…”

Section: Discussionmentioning

confidence: 55%

Based on Network Pharmacology and Molecular Dynamics Simulations, Baicalein, an Active Ingredient of Yiqi Qingre Ziyin Method, Potentially Protects Patients With Atrophic Rhinitis From Cognitive Impairment

Kang

Sun

et al. 2022

Front. Aging Neurosci.

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Cognition may be improved by the active ingredients of the Yiqi Qingre Ziyin method in patients with atrophic rhinitis (AR). This study aimed to identify potential targets of the Yiqi Qingre Ziyin method for the treatment of patients with cognitive impairment. Nasal mucosal tissue samples from patients with AR were subjected to proteomic assays, and differentially expressed proteins were obtained. To explore the mechanism of AR leading to mild cognitive impairment (MCI), a differential analysis of AR related differential proteins in the MCI related GSE140831 dataset was performed. Most AR-related differential proteins are also differentially expressed in peripheral blood tissues of MCI, have similar biological functions and are enriched in similar pathways. These co-expressed differential factors in AR and MCI are known as common differential proteins of AR and MCI (CDPAM). Based on the analysis and validation of the random forest, support vector machine and neural network models, CDPAM acted as a diagnostic marker for MCI risk. Cytochrome C (CYCS) was significantly upregulated in the peripheral blood of patients with MCI. The active ingredients in the Yiqi Qingre Ziqin method were obtained and targeted 137 proteins. Among these targeted proteins, CYCS belong to the CDPAM set. Molecular docking and molecular dynamics analysis revealed that baicalein, an active ingredient in the Yiqi Qingre Ziyin method, stably targeted the CYCS protein. Results of the enrichment analysis revealed that the up-regulation of CYCS expression may have a defensive effect on the cells to resist foreign stimuli. Therefore, baicalein, an active ingredient in the Yiqi Qingre Ziyin method, may prevent the development and progression of MCI by targeting the CYCS protein.

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“…Inmazeb is currently the available drug for treating EVD, with its compounds showing docking scores ranging from -8.0 to -8.8Kcal/mol according to the literature [20]. However, this medication is associated with side effects such as chills, faster heartbeat, vomiting, and tachypnea [21].…”

Section: Discussionmentioning

confidence: 99%

In-silico Screening ofOriganum vulgarePhytocompounds as Potential Drug Agents AgainstVp35Protein of the Ebola Virus

Saeed

Ashraf

Sabir

et al. 2023

Preprint

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The leading cause of the Ebola virus outbreak during 2013-16 in Western Africa was a lack of targeted anti-viral drug choices, a fast rate of mutations and the unavailability of many of the structural proteins and annotations within its genome. The surroundings of the Ebola River in DR-Congo fail to get rid of this endemic, the reason behind this was believed to be its origin from non-human primates, which made its risk assessment and tracing difficult. The Vp35 is a multifunctional protein with innate immune antagonistic properties and is considered one of the most suitable drug targets within this virus. The main motive of this study is to discover a potential anti-viral drug against the Ebola virus by targeting the aforementioned protein with different phytocompounds of oregano that have the lowest binding energies and qualifies over different simulation parameters, so firstly, molecular docking was performed on its 28 compounds using PyRx to get the best complexes with minimum binding energies e.g., -8.9Kcal/mol. Ligands with the best docking scores were gone through Lipinski's rule of five for drug likeliness potential. For the drug affirmation, molecular dynamic simulation was also performed with the best two docked complexes using NAMD/VMD to find out their conformational stability through RMSD, RMSF, Rg, SASA and H-bond analyses. Current computer-generated prediction suggested that Ursolic acid and Oleanolic acid possess potential inhibitory effects against virus replication. Furthermore, paradigm shifts of usage of natural and herbal products for treating infectious diseases are being encouraged here, However, further wet-lab experiments and clinical trials are still needed to determine the robustness of these virtually tested phytocompounds against the Vp35 protein of the Ebola virus.

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Computational Study on Potential Novel Anti-Ebola Virus Protein VP35 Natural Compounds

Cited by 15 publications

References 135 publications

Cheminformatics-Based Study Identifies Potential Ebola VP40 Inhibitors

Cheminformatics-Based Study Identifies Potential Ebola VP40 Inhibitors

Based on Network Pharmacology and Molecular Dynamics Simulations, Baicalein, an Active Ingredient of Yiqi Qingre Ziyin Method, Potentially Protects Patients With Atrophic Rhinitis From Cognitive Impairment

In-silico Screening ofOriganum vulgarePhytocompounds as Potential Drug Agents AgainstVp35Protein of the Ebola Virus

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