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Molecular encapsulation of andrographolide in 2-hydroxypropyl-β-cyclodextrin cavity: synthesis, characterization, pharmacokinetic and in vitro antiviral activity analysis against SARS-CoV-2.

ABSTRACT: In present investigation, AND-2-HyP-β-CYD (Andrographolide-2-Hydroxypropyl-β-cyclodextrin) complex was synthesized and characterized for antiviral and pharmacokinetic profile. The linear host-guest relation suggested synthesis of a 1:1 complex of AND with 2-HyP-β-CYD by inclusion mode. The Kc, stability constant of the two phase system of AND with 2-HyP-β-CYD computed to be 38.60 x 10^-3M. ¹H NMR spectrum of AND indicated the presence of triplet at 6.63-ppm which was up-fielded in AND-2-HyP-β-CYD complex at 6.60-ppm (doublet) confirmed the insertion of AND in cavity of 2-HyP-β-CYD through lactone ring. AND-2-HyP-β-CYD complex exhibited the IC₅₀ of 0.1-μg.mL^-1 (E gene) and 0.29-μg.mL^-1 (N gene) against SARS-CoV-2 infected Vero6 cells. Moreover, a 1.5-fold increment in extent of absorption of AND was noticed post complexation. The bioavailability was estimated to be 15.87 ± 3.84% and 23.84 ± 5.46%, respectively for AND and AND-2-HyP-β-CYD complex. AND-2-HyP-β-CYD complex may be a prospective candidate for further studies to evolve as a clinically viable formulation against SARS-CoV-2.

SUBMITTER: Singh SC

PROVIDER: S-EPMC8351079 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Molecular encapsulation of andrographolide in 2-hydroxypropyl-β-cyclodextrin cavity: synthesis, characterization, pharmacokinetic and in vitro antiviral activity analysis against SARS-CoV-2.

Singh Shashi Chandrama SC Khatri Dharmendra Kumar DK Singh Kulbhaskar K Kanchupalli Vinay Kumar VK Madan Jitender J Singh Shashi Bala SB Singh Harshpal H

Heliyon 20210809 8

In present investigation, AND-2-HyP-β-CYD (Andrographolide-2-Hydroxypropyl-β-cyclodextrin) complex was synthesized and characterized for antiviral and pharmacokinetic profile. The linear host-guest relation suggested synthesis of a 1:1 complex of AND with 2-HyP-β-CYD by inclusion mode. The Kc, stability constant of the two phase system of AND with 2-HyP-β-CYD computed to be 38.60 x 10-3M. 1H NMR spectrum of AND indicated the presence of triplet a ...[more]

PMID: 34395929

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Project description:COVID-19 is marked by extensive damage to the respiratory system, often accompanied by systemic manifestations, due to both viral cytopathic effects and hyperinflammatory syndrome. Therefore, the development of new therapeutic strategies or drug repurposing aiming to control virus replication and inflammation are required to mitigate the impact of the disease. Hydroxypropyl-beta-cyclodextrin (HP-BCD) is a cholesterol-sequestering agent with antiviral activity that has been demonstrated against enveloped viruses in in vitro and in vivo experimental models. We also demonstrated that HP-BCD has an immunomodulatory effect, inhibiting the production of selected proinflammatory cytokines induced by microbial products. Importantly, this drug has been used in humans for decades as an excipient in drug delivery systems and as a therapeutic agent in the treatment of Niemann pick C disease. The safety profile for this compound is well established. Here, we investigated whether HP-BCD would affect SARS-CoV-2 replication and virus-induced inflammatory response, using established cell lines and primary human cells. Treating virus or cells with HP-BCD significantly inhibited SARS-CoV-2 replication with a high selective index. A broad activity against distinct SARS-CoV-2 variants was evidenced by a remarkable reduction in the release of infectious particles. The drug did not alter ACE2 surface expression, but affected cholesterol accumulation into intracellular replication complexes, lowering virus RNA and protein levels, and reducing virus-induced cytopathic effects. Virus replication was also impaired by HP-BCD in Calu-3 pulmonary cell line and human primary monocytes, in which not only the virus, but also the production of proinflammatory cytokines were significantly inhibited. Given the pathophysiology of COVID-19 disease, these data indicate that the use HP-BCD, which inhibits both SARS-CoV2 replication and production of proinflammatory cytokines, as a potential COVID-19 therapeutic warrants further investigation.

Dataset Information

Molecular encapsulation of andrographolide in 2-hydroxypropyl-β-cyclodextrin cavity: synthesis, characterization, pharmacokinetic and in vitro antiviral activity analysis against SARS-CoV-2.

Publications

Molecular encapsulation of andrographolide in 2-hydroxypropyl-<i>β</i>-cyclodextrin cavity: synthesis, characterization, pharmacokinetic and <i>in vitro</i> antiviral activity analysis against SARS-CoV-2.

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