Synthetic derivatives of the antifungal drug ciclopirox are active against herpes simplex virus 2

Zangi, Maryam; Donald, Katherine A.; Casals, Andreu Gazquez; Franson, Abaigeal D.; Yu, Alice J.; Marker, Elise M.; Woodson, Molly; Campbell, Scott; Mottaleb, M. Abdul; Kumar, Tanguturi Venkata Narayana Hajay; Reddy, Makala Shakar; Reddy, L. Vijaya Raghava; Sadhukhan, Subir Kumar; Griggs, David W.; Morrison, Lynda A.; Meyers, Marvin J.

doi:10.1016/j.ejmech.2022.114443

Cited by 9 publications

(6 citation statements)

References 36 publications

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“…The FBDD resulted in the development of potent HBV capsid inhibitors with a binding affinity score to the HBV capsid protein higher than that observed in Ciclopirox complexed with HBV core. Similarly, Zangi et al demonstrated that the development of the core fragments of Ciclopirpx into novel derivatives might reduce HSV-1 and HSV-2 replication more than 1000-fold in vitro [ 24 ]. Therefore, the reconstruction of Ciclopirox enhances its therapeutic activities.…”

Section: Discussionmentioning

confidence: 99%

“…Ciclopirox is a hydroxypyridone antifungal agent with therapeutic functions in cancer [19,20], ischemic stroke [21], and oral candidiasis [22]. Further studies have also shown that the ethanolamine salt of Ciclopirox has antiviral properties against human Herpes Simplex Viruses (HSV-1 & HSV-2) [23,24]. Therefore, reconstruction of Ciclopirox, a low molecular weight chemical compound with 32 atoms, as a chemical starting point, into more potent drug-like leads with higher affinity to the HBV core protein is a promising approach.…”

Section: Introductionmentioning

confidence: 99%

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A fragment-based drug discovery developed on ciclopirox for inhibition of Hepatitis B virus core protein: An in silico study

Mohebbi,

Ghorbanzadeh,

Naderifar

et al. 2023

PLoS ONE

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The Hepatitis B virus (HBV) core protein is an attractive target for preventing capsid assembly and viral replication. Drug repurposing strategies have introduced several drugs targeting HBV core protein. This study used a fragment-based drug discovery (FBDD) approach to reconstruct a repurposed core protein inhibitor to some novel antiviral derivatives. Auto Core Fragment in silico Screening (ACFIS) server was used for deconstruction-reconstruction of Ciclopirox in complex with HBV core protein. The Ciclopirox derivatives were ranked based on their free energy of binding (ΔGB). A quantitative structure affinity relationship (QSAR) was established on the Ciclopirox derivatives. The model was validated by a Ciclopirox-property-matched decoy set. A principal component analysis (PCA) was also assessed to define the relationship of the predictive variable of the QSAR model. 24-derivatives with a ΔGB (-16.56±1.46 Kcal.mol-1) more than Ciclopirox was highlighted. A QSAR model with a predictive power of 88.99% (F-statistics = 9025.78, corrected df(25), Pr > F = 0.0001) was developed by four predictive descriptors (ATS1p, nCs, Hy, F08[C-C]). The model validation showed no predictive power for the decoy set (Q2 = 0). No significant correlation was observed between predictors. By directly attaching to the core protein carboxyl-terminal domain, Ciclopirox derivatives may be able to suppress HBV virus assembly and subsequent viral replication inhibition. Hydrophobic residue Phe23 is a critical amino acid in the ligand binding domain. These ligands share the same physicochemical properties that lead to the development of a robust QSAR mode. The same strategy may also be used for future drug discovery of viral inhibitors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A fragment-based drug discovery developed on ciclopirox for inhibition of Hepatitis B virus core protein: An in silico study

Mohebbi,

Ghorbanzadeh,

Naderifar

et al. 2023

PLoS ONE

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“…IR spectroscopy is often used in the context of research in medicine, biotechnology, and pharmacy [ 54 , 55 , 56 ].…”

Section: Medicinementioning

confidence: 99%

The Analytical Possibilities of FT-IR Spectroscopy Powered by Vibrating Molecules

Koczoń

Hołaj-Krzak

Palani

et al. 2023

IJMS

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This paper discusses the state of advancement in the development of spectroscopic methods based on the use of mid (proper) infrared radiation in the context of applications in various fields of science and technology. The authors drew attention to the most important solutions specific to both spectroscopy itself (ATR technique) and chemometric data processing tools (PCA and PLS models). The objective of the current paper is to collect and consistently present information on various aspects of FT-IR spectroscopy, which is not only a well-known and well-established method but is also continuously developing. The innovative aspect of the current review is to show FT-IR’s great versatility that allows its applications to solve and explain issues from both the scientific domain (e.g., hydrogen bonds) and practical ones (e.g., technological processes, medicine, environmental protection, and food analysis). Particular attention was paid to the issue of hydrogen bonds as key non-covalent interactions, conditioning the existence of living matter and determining the number of physicochemical properties of various materials. Since the role of FT-IR spectroscopy in the field of hydrogen bond research has great significance, a historical outline of the most important qualitative and quantitative hydrogen bond theories is provided. In addition, research on selected unconventional spectral effects resulting from the substitution of protons with deuterons in hydrogen bridges is presented. The state-of-the-art and originality of the current review are that it presents a combination of uses of FT-IR spectroscopy to explain the way molecules vibrate and the effects of those vibrations on macroscopic properties, hence practical applications of given substances.

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“…Ciclopirox strongly inhibits the replication of HSV1 and HSV2. Ciclopirox blocks the enzymatic activity of the nucleotidyl transferase superfamily, which is essential for HSV replication 25 , 26 . Several studies have reported that ciclopirox effectively inhibits HIV replication.…”

Section: Introductionmentioning

confidence: 99%

Ciclopirox inhibits SARS-CoV-2 replication by promoting the degradation of the nucleocapsid protein

Wei,

Zhou,

Shen

et al. 2024

Acta Pharmaceutica Sinica B

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Synthetic derivatives of the antifungal drug ciclopirox are active against herpes simplex virus 2

Cited by 9 publications

References 36 publications

A fragment-based drug discovery developed on ciclopirox for inhibition of Hepatitis B virus core protein: An in silico study

A fragment-based drug discovery developed on ciclopirox for inhibition of Hepatitis B virus core protein: An in silico study

The Analytical Possibilities of FT-IR Spectroscopy Powered by Vibrating Molecules

Ciclopirox inhibits SARS-CoV-2 replication by promoting the degradation of the nucleocapsid protein

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