Repurposing clinical drugs is a promising strategy to discover drugs against Zika virus infection

Song, Weibao; Zhang, Hongjuan; Zhang, Yu; Li, Rui; Han, Yan‐Xing; Lin, Yuan; Jiang, Jian‐Dong

doi:10.1007/s11684-021-0834-9

Cited by 13 publications

(8 citation statements)

References 107 publications

(143 reference statements)

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“…However, 1e showed equivalent binding energy of −6.675 ± 0.05 kcal/mol and K i of 12.67519392 ± 1.115312 μM for RNA-dependent RNA polymerase, while 4e showed equivalent binding energy of −7.6 ± 0.00 kcal/mol and K i of 2.648363028 ± 0.000000 μM for NS5-methyltransferase when compared with efavirenz, 3e, (−6.60 ± 0.00 kcal/mol and 14.34816176 ± 0.000000 μM for RNA-dependent RNA polymerase; −7.43 ± 0.05 kcal/mol and 3.568824547 ± 0.288630 μM for NS5-methyltransferase) (Supporting Information 1). Previous studies have reported inhibitors of the zika virus replication/NS5-RNA-dependent RNA polymerase and/or NS5-methyltransferase 2,13,[15][16][17][18][19]36,47,48 using various strategies. This study identified some derivatives of the said parent compounds as potential inhibitors of the virus NS5 protein, and a previous report had validated N- [4-[6-tert-butyl-5methoxy-8-(6-methoxy-2-oxo-1H-pyridin-3-yl)-3 quinolyl] phenyl] methanesulfonamide (PubChem identifier: CID 49835560), a derivative of dasabuvir, against hepatitis C virus NS5B polymerase 44 but not zika virus.…”

Section: ■ Introductionmentioning

confidence: 99%

Chemoinformatic Design and Profiling of Derivatives of Dasabuvir, Efavirenz, and Tipranavir as Potential Inhibitors of Zika Virus RNA-Dependent RNA Polymerase and Methyltransferase

et al. 2022

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Zika virus (ZIKV) infection is one of the mosquito-borne flaviviruses of human importance with more than 2 million suspected cases and more than 1 million people infected in about 30 countries. There are reported inhibitors of the zika virus replication machinery, but no approved effective antiviral therapy including vaccines directed against the virus for treatment or prevention is currently available. The study investigated the chemoinformatic design and profiling of derivatives of dasabuvir, efavirenz, and tipranavir as potential inhibitors of the zika virus RNA-dependent RNA polymerase (RdRP) and/or methyltransferase (MTase). The three-dimensional (3D) coordinates of dasabuvir, efavirenz, and tipranavir were obtained from the PubChem database, and their respective derivatives were designed with DataWarrior-5.2.1 using an evolutionary algorithm. Derivatives that were not mutagenic, tumorigenic, or irritant were selected; docked into RdRP and MTase; and further subjected to absorption, distribution, metabolism, excretion, and toxicity (ADMET) evaluation with Swiss-ADME and pkCSM web tools. Some of the designed compounds are Lipinski’s rule-of-five compliant, with good synthetic accessibilities. Compounds 20d , 21d , 22d , and 1e are nontoxic with the only limitation of CYP1A2, CYP2C19, and/or CYP2C9 inhibition. Replacements of −CH 3 and −NH– in the methanesulfonamide moiety of dasabuvir with −OH and −CH 2 – or −CH 2 CH 2 –, respectively, improved the safety/toxicity profile. Hepatotoxicity in 5d , 4d , and 18d is likely due to −NH– in their methanesulfonamide/sulfamic acid moieties. These compounds are potent inhibitors of N-7 and 2′-methylation activities of ZIKV methyltransferase and/or RNA synthesis through interactions with amino acid residues in the priming loop/“N-pocket” in the virus RdRP. Synthesis of these compounds and wet laboratory validation against ZIKV are recommended.

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Section: ■ Introductionmentioning

confidence: 99%

Chemoinformatic Design and Profiling of Derivatives of Dasabuvir, Efavirenz, and Tipranavir as Potential Inhibitors of Zika Virus RNA-Dependent RNA Polymerase and Methyltransferase

et al. 2022

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“…While keeping this in mind, we should, however, understand that there have been various approaches implemented by the scientists across the world to develop novel formulations that could be useful as antiviral medications to deal with COVID-19. One of the most useful strategies is repurposing [19][20][21] already existing FDA-approved drug candidates involving biomaterials, such as organic or inorganic ones, in order to improve their therapeutic efficacy. However, one has to rationally select highly biocompatible and efficient drug carriers to selectively target the infected cells, and thereby minimize the side effects on the unaffected cells or tissues.…”

Section: Introductionmentioning

confidence: 99%

Bovine Serum Albumin-Coated Niclosamide-Zein Nanoparticles as Potential Injectable Medicine against COVID-19

Choi

Piao

2021

Materials

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(1) Background: COVID-19 has affected millions of people worldwide, but countries with high experimental anti-SARS-CoV-2 vaccination rates among the general population respectively show progress in achieving general herd immunity in the population (a combination of natural and vaccine-induced acquired immunity), resulting in a significant reduction in both newly detected infections and mortality rates. However, the longevity of the vaccines’ ability to provide protection against the ongoing pandemic is still unclear. Therefore, it is of utmost importance to have new medications to fight against the pandemic at the earliest point possible. Recently, it has been found that repurposing already existing drugs could, in fact, be an ideal strategy to formulate effective medication for COVID-19. Though there are many FDA-approved drugs, it has been found that niclosamide (NIC), an anthelmintic drug, has significantly high potential against the SARS-CoV-2 virus. (2) Methods: Here we deployed a simple self-assembling technique through which Zein nanoparticles were successfully used to encapsulate NIC, which was then coated with bovine serum albumin (BSA) in order to improve the drugs’ stability, injectablity, and selectivity towards the virus-infected cells. (3) Results: The particle size for the BSA-stabilized Zein-NIC nanohybrid was found to be less than 200 nm, with excellent colloidal stability and sustained drug release properties. In addition, the nanohybrid showed enhanced drug release behavior under serum conditions, indicating that such a hybrid drug delivery system could be highly beneficial for treating COVID-19 patients suffering from high endothelial glycocalyx damage followed by a cytokine storm related to the severe inflammations.

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“…The systematic review was conducted following the Cochrane Handbook principles and was based on similar previous studies 32,36–38 . The search, selection of studies, data extraction, and analysis of the results were performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement 39 …”

Section: Methodsmentioning

confidence: 99%

“…The systematic review was conducted following the Cochrane Handbook principles and was based on similar previous studies. 32,[36][37][38] The search, selection of studies, data extraction, and analysis of the results were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. 39 Studies that identified compounds that target the NS2B-NS3 pro of ZIKV were screened using PubMed/MEDLINE and Scopus databases (last search: June 24, 2021).…”

Section: Search Strategiesmentioning

confidence: 99%

NS2B‐NS3 protease inhibitors as promising compounds in the development of antivirals against Zika virus: A systematic review

Nunes

Santos

Fonseca

et al. 2021

Journal of Medical Virology

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Zika virus (ZIKV) infections are associated with severe neurological complications and are a global public health concern. There are no approved vaccines or antiviral drugs to inhibit ZIKV replication. NS2B-NS3 protease (NS2B-NS3 pro), which is essential for viral replication, is a promising molecular target for anti-ZIKV drugs. We conducted a systematic review to identify compounds with promising effects against ZIKV; we discussed their pharmacodynamic and pharmacophoric characteristics. The online search, performed using the PubMed/MEDLINE and SCOPUS databases, yielded 56 articles; seven relevant studies that reported nine promising compounds with inhibitory activity against ZIKV NS2B-NS3 pro were selected. Of these, five (niclosamide, nitazoxanide, bromocriptine, temoporfin, and novobiocin) are currently available on the market and have been tested for off-label use against ZIKV. The 50% inhibitory concentration values of these compounds for the inhibition of NS2B-NS3 pro ranged at 0.38-21.6 µM; most compounds exhibited noncompetitive inhibition (66%). All compounds that could inhibit the NS2B-NS3 pro complex showed potent in vitro anti-ZIKV activity with a 50% effective concentration ranging 0.024-50 µM. The 50% cytotoxic concentration of the compounds assayed using A549, Vero, and WRL-69 cell lines ranged at 0.6-1388.02 µM and the selectivity index was 3.07-1698. This review summarizes the most promising antiviral agents against ZIKV that have inhibitory activity against viral proteases.

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Repurposing clinical drugs is a promising strategy to discover drugs against Zika virus infection

Cited by 13 publications

References 107 publications

Chemoinformatic Design and Profiling of Derivatives of Dasabuvir, Efavirenz, and Tipranavir as Potential Inhibitors of Zika Virus RNA-Dependent RNA Polymerase and Methyltransferase

Chemoinformatic Design and Profiling of Derivatives of Dasabuvir, Efavirenz, and Tipranavir as Potential Inhibitors of Zika Virus RNA-Dependent RNA Polymerase and Methyltransferase

Bovine Serum Albumin-Coated Niclosamide-Zein Nanoparticles as Potential Injectable Medicine against COVID-19

NS2B‐NS3 protease inhibitors as promising compounds in the development of antivirals against Zika virus: A systematic review

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