Pharmaceutically Acceptable Carboxylic Acid-Terminated Polymers Show Activity and Selectivity against HSV-1 and HSV-2 and Synergy with Antiviral Drugs

Yadavalli, Tejabhiram; Mallick, Sudipta; Patel, Pratikkumar; Koganti, Raghuram; Shukla, Deepak; Date, Abhijit A.

doi:10.1021/acsinfecdis.0c00368

Cited by 13 publications

(11 citation statements)

References 44 publications

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“…Decoying polymeric scaffolds with carboxylate and carboxylic acid moieties have been shown to introduce antiviral activity by inhibiting the viral entry to the host cells. , It has been shown that the FDA-approved cellulose acetate phthalate in the regular and nanoparticle (NP) form has selectivity and antiviral activity against HSV types 1 and 2, although their exact mechanism of action is under further investigation …”

Section: Introductionmentioning

confidence: 99%

“…19,20 It has been shown that the FDA-approved cellulose acetate phthalate in the regular and nanoparticle (NP) form has selectivity and antiviral activity against HSV types 1 and 2, although their exact mechanism of action is under further investigation. 21 Negatively charged polysaccharides, with similar structures to HS like heparin, have been used as binding decoys to prevent HSV-1 infection. 22,23 However, clinical application of heparin as an antiherpetic drug is limited because of its heterogeneity and possible impurities.…”

Section: ■ Introductionmentioning

confidence: 99%

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Inhibition of Herpes Simplex Virus Type 1 Attachment and Infection by Sulfated Polyglycerols with Different Architectures

et al. 2021

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Inhibition of herpes simplex virus type 1 (HSV-1) binding to the host cell surface by highly sulfated architectures is among the promising strategies to prevent virus entry and infection. However, the structural flexibility of multivalent inhibitors plays a major role in effective blockage and inhibition of virus receptors. In this study, we demonstrate the inhibitory effect of a polymer scaffold on the HSV-1 infection by using highly sulfated polyglycerols with different architectures (linear, dendronized, and hyperbranched). IC 50 values for all synthesized sulfated polyglycerols and the natural sulfated polymer heparin were determined using plaque reduction infection assays. Interestingly, an increase in the IC 50 value from 0.03 to 374 nM from highly flexible linear polyglycerol sulfate (LPGS) to less flexible scaffolds, namely, dendronized polyglycerol sulfate and hyperbranched polyglycerol sulfate was observed. The most potent LPGS inhibits HSV-1 infection 295 times more efficiently than heparin, and we show that LPGS has a much reduced anticoagulant capacity when compared to heparin as evidenced by measuring the activated partial thromboplastin time. Furthermore, prevention of infection by LPGS and the commercially available drug acyclovir were compared. All tested sulfated polymers do not show any cytotoxicity at concentrations of up to 1 mg/mL in different cell lines. We conclude from our results that more flexible polyglycerol sulfates are superior to less flexible sulfated polymers with respect to inhibition of HSV-1 infection and may constitute an alternative to the current antiviral treatments of this ubiquitous pathogen.

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Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Inhibition of Herpes Simplex Virus Type 1 Attachment and Infection by Sulfated Polyglycerols with Different Architectures

et al. 2021

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Section: Hs Mimetics As Viral Inhibitorsmentioning

confidence: 98%

“…Shortly after this study, Yadavalli and co-workers demonstrated that three previously FDA-approved polycarboxylates used for coating drugs in oral formulations,PVAP (poly(vinyl acetate phthalate)), HPMCP-55S (hydroxypropylmethylcellulose phthalate), and Eudragit S100 (methacrylic acid methyl methacrylate copolymer, ratio 1:2)exhibited antiviral activity against HSV infections . Whereas HPMCP-55S was active against both HSV-1 and HSV-2, PVAP only showed neutralizing activity against HSV-1 infections, while Eudragit S100 only showed significant antiviral efficacy against HSV-2, indicating a potential selectivity of the different polyanions against different viruses …”

Section: Hs Mimetics As Viral Inhibitorsmentioning

confidence: 99%

“…218 Whereas HPMCP-55S was active against both HSV-1 and HSV-2, PVAP only showed neutralizing activity against HSV-1 infections, while Eudragit S100 only showed significant antiviral efficacy against HSV-2, indicating a potential selectivity of the different polyanions against different viruses. 218 To the best of our knowledge, the only examples of nonsaccharide-based polymeric HP mimetics targeting SARS-CoV-2 were published by Nie and co-workers. 154 Here, in a similar fashion to their work on HSV, the potential to inhibit SARS-CoV-2 infection for LPGS and HPGS was evaluated with plaque reduction assays and compared to HP and pentosan sulfate.…”

Section: Role Of Hp and Hs In Viralmentioning

confidence: 99%

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Polymers Inspired by Heparin and Heparan Sulfate for Viral Targeting

2022

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Heparin (HP) and heparan sulfate (HS) are linear, anionically charged polysaccharides well-known for their diverse biological activities. While HP is generally localized in mast cells and in connective tissues, HS is part of the glycocalyx and involved in the attachment of viruses to host cells, constituting the first step of an infection. HP and HS also exhibit antiviral activity by blocking viral receptors, thereby inhibiting viruses from engaging with host cells. Inspired by their structural features, such as their high molecular weight and polyanionic character, various synthetic polymers mimicking HP/HS have been developed and used as model systems to study bioactivity, as well as for therapeutic applications. This Perspective provides an overview of the roles of HP/HS in viral engagement, and examines historical and recent approaches toward oligo-/polysaccharide, glycopolymer, and anionic polymer HP/HS mimetics. An overview of current applications and future prospects of these molecules is provided, demonstrating their potential in addressing current and future epidemics and pandemics.

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A Review of Synthetic Application of Homogeneous, Heterogenised‐Homogeneous, and Microwave‐Assisted Catalytic Carbonylation of Selected Substrates

Pant,

Prakash,

Dhami

2024

ChemistrySelect

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Catalytic carbonylation has gained a lot of interest over the past 20 years. It produced various pharmaceuticals, agrochemicals, and intermediates that can made through this process. The carbonylation process is the most straightforward method to insert CO into any organic substrate using a simple carbonyl source, i. e., CO gas. Apart from gaseous CO, many techniques have devised for producing CO in situ using surrogates such as HCOOH, DMF, Formic acid, Phenyl Formate, Oxalic acid, and Chloroform. Several carbonylation methods, such as aminocarbonylation, alkoxycarbonylation, double carbonylation, and oxidative carbonylation, provide viable and appealing substitutes for conventional synthetic methods on a commercial or laboratory scale. Many recent studies focus on catalyst‐product separation, catalyst recoverability, and reusability in these reactions. Therefore, advancements in using different approaches, such as supported liquid phase catalysis and biphasic catalysis, to anchor homogeneous catalysts are becoming increasingly important. These carbonylation methods are easy to use, cost‐effective, and do not require ligands. They also produce excellent yields of the products necessary. Using phosphine ligands has drawbacks, including high work‐up costs, laborious work‐up techniques, and sensitivity to air and moisture. Several phosphine‐free carbonylation pathways offer affordable and straightforward ways to accomplish these changes without phosphine ligands. This review summarizes the synthetic application of homogeneous and immobilized catalysts in producing carboxylic acid derivatives and heterocycles that have medicinal properties.

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Pharmaceutically Acceptable Carboxylic Acid-Terminated Polymers Show Activity and Selectivity against HSV-1 and HSV-2 and Synergy with Antiviral Drugs

Cited by 13 publications

References 44 publications

Inhibition of Herpes Simplex Virus Type 1 Attachment and Infection by Sulfated Polyglycerols with Different Architectures

Inhibition of Herpes Simplex Virus Type 1 Attachment and Infection by Sulfated Polyglycerols with Different Architectures

Polymers Inspired by Heparin and Heparan Sulfate for Viral Targeting

A Review of Synthetic Application of Homogeneous, Heterogenised‐Homogeneous, and Microwave‐Assisted Catalytic Carbonylation of Selected Substrates

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