Repurposing antiviral drugs against the human monkeypox virus DNA-dependent RNA polymerase; in silico perspective

Abduljalil, Jameel M.; Elfiky, Abdo A.

doi:10.1016/j.jinf.2022.09.002

Cited by 17 publications

(12 citation statements)

References 3 publications

(1 reference statement)

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“…Since smallpox was the only human infection of medical significance that has been eradicated through vaccination, limited research has been conducted on identifying anti-poxvirus drugs. Based on our previous results [14] , the top 15 natural products from the docking step show lower binding energies (i.e., higher affinities to the DdRp) than the four nucleotide triphosphates, which may indicate promising scaffolds for non-nucleoside inhibitors as seen in other compounds from natural sources [38] , [39] . The interaction of identified compounds with R380 and H385, and the nearby amino acids, is interesting since counterpart residues in the actively transcribing model of the vaccinia virus (PDB: 6RID) are involved in direct contact with the backbone of the DNA strand being transcribed.…”

Section: Discussionmentioning

confidence: 79%

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Exploration of natural compounds against the human mpox virus DNA-dependent RNA polymerase in silico

Abduljalil

Elfiky

Elgohary

2023

Journal of Infection and Public Health

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Section: Discussionmentioning

confidence: 79%

“…In this study, we used the model of hMPXV DdRp, as reported previously [14] . The amino acid sequence of hMPXV DdRp chain A was obtained from the NCBI database (GenBank: AAY97089.1).…”

Section: Methodsmentioning

confidence: 99%

Exploration of natural compounds against the human mpox virus DNA-dependent RNA polymerase in silico

Abduljalil

Elfiky

Elgohary

2023

Journal of Infection and Public Health

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“…Although Methisazone's antiviral activity suggests that the element of replication can be targeted in the development of antiviral drugs, this substance was ineffective at reducing the mortality of cowpox‐infected mice 81 . In a recent study, the molecular docking of two antiviral medications (Norov‐29 and Bemnifosbuvir) against MPXV DNA‐dependent RNA polymerase (DdRp) yielded encouraging results, with binding‐free energy (BFE) of −24.26 ± 4.43 and −21.32 ± 6.43 kcal/mol, respectively, that warrant further investigation 129 . Another in silico study determined that fludarabine (a purine analog used to treat chronic lymphocytic leukemia) had BFE of −7.53 kcal/mol, suggesting that it has the potential to act as an inhibitor of DdRp subunit A6R 130 …”

Section: Monkeypox Therapeutic Drug Targets and Strategiesmentioning

confidence: 99%

Monkeypox outbreak 2022: What we know so far and its potential drug targets and management strategies

Rabaan

Abas

Tallei

et al. 2022

Journal of Medical Virology

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Monkeypox is a rare zoonotic disease caused by infection with the monkeypox virus. The disease can result in flu‐like symptoms, fever, and a persistent rash. The disease is currently spreading throughout the world and prevention and treatment efforts are being intensified. Although there is no treatment that has been specifically approved for monkeypox virus infection, infected patients may benefit from using certain antiviral medications that are typically prescribed for the treatment of smallpox. The drugs are tecovirimat, brincidofovir, and cidofovir, all of which are currently in short supply due to the spread of the monkeypox virus. Resistance is also a concern, as widespread replication of the monkeypox virus can lead to mutations that produce monkeypox viruses that are resistant to the currently available treatments. This article discusses monkeypox disease, potential drug targets, and management strategies to overcome monkeypox disease. With the discovery of new drugs, it is hoped that the problem of insufficient drugs will be resolved, and it is not anticipated that drug resistance will become a major issue in the near future.

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“…We focussed on the mpxvgp158 protein from the monkeypox virus that is known to be crucial for the viral replication cycle. In a recent study, Abduljalil and Elfiky concluded that Norov-29 and bemnifosbuvir, two antiviral drugs, can bind to the active site of DNA dependent RNA polymerase (DdRp) and help in fighting against human monkeypox virus (HMP) 26 demonstrated that eight drugs namely NMCT and rutaecarpine for A48R, fosdagrocorat and lixivaptan for I7L, simeprevir for D13L, nilotinib for A50R, and hypericin and naldemedine for F13L can be potential targets for the inhibition of HMP so that fatalities can be decreased. 27 D9 decapping enzyme and thymidylate kinase (TMPK) enzymes of viruses may also make potent antiviral drugs (Doxorubicin, Cefiderocol, Tipranavir, and Dolutegravir) targets, according to earlier research.…”

Section: Introductionmentioning

confidence: 99%

Tecovirimat as a Potential Bioavailable inhibitor against MPXVgp158 Established through Molecular Dynamic Simulations and Docking Studies

Sharma¹,

Panwar²,

Garg³

et al. 2022

J. Pure Appl. Microbiol.

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Monkeypox is a zoonotic viral infection caused by monkeypox virus which belongs to the Poxviridae family of genus Orthopoxvirus. Usually, the virus transmission happens when the individual comes in contact with the infected person through body fluids, animal lesions, respiratory droplets or through virus contaminated materials. Clinical presentation of the monkeypox has shown significant resemblance to that of smallpox and chickenpox, belonging to the same orthopoxvirus genus but were eradicated during 1980s globally. Monkeypox may lead to a range of medical complications including clinical symptoms like fever, rashes, headaches, back pain, myodynia and swollen lymph nodes. As far as the treatment modalities are concerned, the antiviral therapeutic agents developed for the smallpox treatment, were also permitted to be used for the monkeypox treatment. However, there is no proven treatment for human monkeypox. In the current study, we have focused on designing of a best probable ligand against the target MPXVgp158 (Monkeypox virus protein). Since Tecovirimat is an FDA approved compound known as an antipoxviral drug, the study aimed to develop a Monkeypox virus protein MPXVgp158 inhibitor which is bioavailable and biocompatible as well through drug designing using computational tools. Molecular docking (MD) analysis displayed Tecovirimat with lesser binding energy, higher non-bonded interaction capability, and more stability against MPXVgp158, with efficient binding mode of interactions. Hence, Tecovirimat was adjudged to be the potential candidate against MPXVgp158 inhibition.

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Repurposing antiviral drugs against the human monkeypox virus DNA-dependent RNA polymerase; in silico perspective

Cited by 17 publications

References 3 publications

Exploration of natural compounds against the human mpox virus DNA-dependent RNA polymerase in silico

Exploration of natural compounds against the human mpox virus DNA-dependent RNA polymerase in silico

Monkeypox outbreak 2022: What we know so far and its potential drug targets and management strategies

Tecovirimat as a Potential Bioavailable inhibitor against MPXVgp158 Established through Molecular Dynamic Simulations and Docking Studies

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