In silico evaluation of lapachol derivatives binding to the Nsp9 of SARS-CoV-2

Nicolau-Júnior, Nilson; Santos, Igor Andrade; Meireles, Bruno A.; Nicolau, Mariana Sant’Anna Pereira; Lapa, Igor Rodrigues; Aguiar, Renato Santana; Jardim, Ana Carolina Gomes; José, Diego Pandeló

doi:10.1080/07391102.2021.1875050

Cited by 7 publications

(7 citation statements)

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“…More interestingly, lapachol and its derivatives, which are naphthoquinone derivatives, were recently tested against SARS-CoV-2 using in silico approaches [ 6 ]. In this study, GOLD program was used for molecular docking against Nsp9 of SARS-CoV-2 and lapachol derivative IX showed the highest docking score.…”

Section: Resultsmentioning

confidence: 99%

“…RNA binding site of Nsp9 was reported as a promising drug target to discover potential antiviral compounds. With this approach, potential compounds were identified against dengue virus, Chikungunya virus and SARS-CoV [ 6 ]. After specifying the grid boxes based on predicted druggable pockets, protein and ligand preparations were completed and 6W4B were docked against 1 – 17 using Autodock Vina.…”

Section: Resultsmentioning

confidence: 99%

“…and Tecoma sp., was reported as a potential therapeutic agent with various bioactivities such as anti-inflammatory, analgesic, antimalarial, antischistosomal, antiviral, antitrypanosomal, leishmanicide, antifungal, anticancer and antiulcerative activities [ 5 ]. Additionally, in a recent study, lapachol and its derivatives were screened against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using an in silico approach and some of lapachol derivatives exhibited strong binding affinity to non-structural protein 9 (Nsp9) of SARS-CoV-2, which is one of the potential drug target proteins [ 6 ]. Another natural naphthoquinone is shikonin, which is isolated from Lithospermum erythrorhizon .…”

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confidence: 99%

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Biosynthesis of Novel Naphthoquinone Derivatives in the Commonly-used Chassis Cells Saccharomyces cerevisiae and Escherichia coli

Wang

Zhang

et al. 2021

Appl Biochem Microbiol

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Naphthoquinones harboring 1,4-naphthoquinone pharmacophore are considered as privileged structures in medicinal chemistry. In pharmaceutical industry and fundamental research, polyketide naphthoquinones were widely produced by heterologous expression of polyketide synthases in microbial chassis cells, such as Saccharomyces cerevisiae and Escherichia coli . Nevertheless, these cell factories still remain, to a great degree, black boxes that often exceed engineers’ expectations. In this work, the biotransformation of juglone or 1,4-naphthoquinone was conducted to generate novel derivatives and it was revealed that these two naphthoquinones can indeed be modified by the chassis cells. Seventeen derivatives, including 6 novel compounds, were isolated and their structural characterizations indicated the attachment of certain metabolites of chassis cells to naphthoquinones. Some of these biosynthesized derivatives were reported as potent antimicrobial agents with reduced cytotoxic activities. Additionally, molecular docking as simple and quick in silico approach was performed to screen the biosynthesized compounds for their potential antiviral activity. It was found that compound 11 and 17 showed the most promising binding affinities against Nsp9 of SARS-CoV-2, demonstrating their potential antiviral activities. Overall, this work provides a new approach to generate novel molecules in the commonly used chassis cells, which would expand the chemical diversity for the drug development pipeline. It also reveals a novel insight into the potential of the catalytic power of the most widely used chassis cells. Supplementary Information The online version contains supplementary material available at 10.1134/S0003683821100124.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Biosynthesis of Novel Naphthoquinone Derivatives in the Commonly-used Chassis Cells Saccharomyces cerevisiae and Escherichia coli

Wang

Zhang

et al. 2021

Appl Biochem Microbiol

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“…good binding energies and stable dynamics with the target protein. [128] 8 | OTHERS Crytospirolepine, 10ʹ-hydroxyusambaresine, strychnopentamine, usararotenoid A and 12α-epi-milletosin showed good binding affinity towards inhibition of RdRp of SARS-CoV-2. Here, the best molecules that were found through in silico studies were compiled and they need to be studied further for effective drug development.…”

Section: Sars-covmentioning

confidence: 99%

Implication of in silico studies in the search for novel inhibitors against SARS‐CoV‐2

Ali¹,

Alom²,

Shakya

et al. 2022

Archiv der Pharmazie

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Corona Virus Disease-19 (COVID-19) is a pandemic disease mainly caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It had spread from Wuhan, China, in late 2019 and spread over 222 countries and territories all over the world. Earlier, at the very beginning of COVID-19 infection, there were no approved medicines or vaccines for combating this disease, which adversely affected a lot of individuals worldwide. Although frequent mutation leads to the generation of more deadly variants of SARS-CoV-2, researchers have developed several highly effective vaccines that were approved for emergency use by the World Health Organization (WHO), such as mRNA-1273 by Moderna, BNT162b2 by Pfizer/BioNTech, Ad26.-COV2.S by Janssen, AZD1222 by Oxford/AstraZeneca, Covishield by the Serum Institute of India, BBIBP-CorV by Sinopharm, coronaVac by Sinovac, and Covaxin by Bharat Biotech, and the first US Food and Drug Administration-approved antiviral drug Veklury (remdesivir) for the treatment of COVID-19. Several waves of COVID-19 have already occurred worldwide, and good-quality vaccines and medicines should be available for ongoing as well as upcoming waves of the pandemic.Therefore, in silico studies have become an excellent tool for identifying possible ligands that could lead to the development of safer medicines or vaccines. Various phytoconstituents from plants and herbs with antiviral properties are studied further to obtain inhibitors of SARS-CoV-2. In silico screening of various molecular databases like PubChem, ZINC, Asinex Biol-Design Library, and so on has been performed extensively for finding effective ligands against targets. Herein, in silico studies carried out by various researchers are summarized so that one can easily find the best molecule for further in vitro and in vivo studies.

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“…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 ). 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.

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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.

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In silico evaluation of lapachol derivatives binding to the Nsp9 of SARS-CoV-2

Cited by 7 publications

References 60 publications

Biosynthesis of Novel Naphthoquinone Derivatives in the Commonly-used Chassis Cells Saccharomyces cerevisiae and Escherichia coli

Biosynthesis of Novel Naphthoquinone Derivatives in the Commonly-used Chassis Cells Saccharomyces cerevisiae and Escherichia coli

Implication of in silico studies in the search for novel inhibitors against SARS‐CoV‐2

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

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