Investigational drugs in early development for treating dengue infection

Beesetti, Hemalatha; Khanna, Navin; Swaminathan, Sathyamangalam

doi:10.1080/13543784.2016.1201063

Cited by 22 publications

(19 citation statements)

References 74 publications

(112 reference statements)

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“…Thus, a drug for treating dengue illness is an unmet public health need. Current dengue drug discovery efforts are based either on high throughput screening of compound libraries for potential antiviral inhibitors or re-purposing of existing clinical compounds which have been developed previously for other disease indications [15].…”

Section: Discussionmentioning

confidence: 99%

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A Quinoline Compound Inhibits the Replication of Dengue virus Serotypes 1–4 in Vero Cells

et al. 2017

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Section: Discussionmentioning

confidence: 99%

“…Introduction drug development [15]. Thus, celgosivir, a drug initially intended for treating HCV infection, was tested for antiviral efficacy against dengue.…”

Section: Original Article a Quinoline Compound Inhibits The Replication Of Dengue Virus Serotypes 1-4 In Vero Cellsmentioning

confidence: 99%

A Quinoline Compound Inhibits the Replication of Dengue virus Serotypes 1–4 in Vero Cells

et al. 2017

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“…Corticosteroid is mainly adopted as an adjunct immunomodulatory treatment for diseases caused by immune responses [48]. Immune pathology of dengue has similarities to other autoimmune diseases that have been successfully treated by corticosteroids [48,62]. A clinical trial has shown the supportive evidence for the actions of methylprednisolone to prevent dengue progression to DHF or DSS [63].…”

Section: Drug Repurposing For Dengue Therapymentioning

confidence: 99%

Structure-Based Design of Antivirals against Envelope Glycoprotein of Dengue Virus

Anasir

Ramanathan

Poh

2020

Viruses

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Dengue virus (DENV) presents a significant threat to global public health with more than 500,000 hospitalizations and 25,000 deaths annually. Currently, there is no clinically approved antiviral drug to treat DENV infection. The envelope (E) glycoprotein of DENV is a promising target for drug discovery as the E protein is important for viral attachment and fusion. Understanding the structure and function of DENV E protein has led to the exploration of structure-based drug discovery of antiviral compounds and peptides against DENV infections. This review summarizes the structural information of the DENV E protein with regards to DENV attachment and fusion. The information enables the development of antiviral agents through structure-based approaches. In addition, this review compares the potency of antivirals targeting the E protein with the antivirals targeting DENV multifunctional enzymes, repurposed drugs and clinically approved antiviral drugs. None of the current DENV antiviral candidates possess potency similar to the approved antiviral drugs which indicates that more efforts and resources must be invested before an effective DENV drug materializes.

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“…Though several attempts have been made for development of drugs against dengue, the efforts have not yielded a safe and effective drug so far. [16][17][18]. Several drugs such as chloroquine [19], celgosivir [20], lovastatin [21], balapiravir [22], prednisolone [23] have been evaluated for their ability to treat dengue infection and disease.…”

Section: Introductionmentioning

confidence: 99%

Cocculus hirsutus-derived phytopharmaceutical drug has potent anti-dengue activity

Poddar

Beesetti

Arora

et al. 2020

Preprint

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BackgroundDengue is a serious public health concern worldwide, with ~3 billion people at risk of contracting dengue virus (DENV) infections. Currently, no effective vaccine or drug is available for the prevention or treatment of dengue, which leaves only anti-mosquito strategies to combat this disease. The present study was initiated to determine the in-vitro and in vivo protective effects of a plant-derived phytopharmaceutical drug for the treatment of dengue.Methodology/Principal FindingsIn our previous report, we had identified methanolic extract of the aerial parts of Cissampelos pareira to exhibit in vitro and in vivo anti-dengue activity against all the four DENV serotypes. In the current study, we have identified another Indian medicinal plant, Cocculus hirsutus, which has a more potent anti-dengue activity than C. pareira. The activity has been evaluated through flow-cytometry-based virus inhibition assay. Interestingly, the stem of C. hirsutus was found to be more potent than the aerial part irrespective of the extraction solvent used viz., denatured spirit, hydro-alcohol (50:50) and water. Hence, the aqueous extract of stem of C. hirsutus (AQCH) was further advanced for investigations because of greater regulatory acceptance. The AQCH exhibited dose-dependent inhibition of release of DENV and its secretory antigen, NS1. Five chemical markers viz. Sinococuline, 20-Hydroxyecdysone, Makisterone-A, Magnoflorine and Coniferyl alcohol were identified as the major chemical ingredients of the AQCH extract. These chemicals were subsequently used for extract standardisation. Importantly, AQCH completely protected AG129 mice at 25 mg/kg/dose body weight when fed 4 times a day post-infection with a lethal dose of DENV-2 S221 strain. Because of its potential as an effective phytopharmaceutical drug against dengue, AQCH, has been formulated into tablets for further pre-clinical and clinical developments.Conclusions/SignificanceWe provide evidence of the pan anti-dengue potential of C. hirsutus-based phytopharmaceutical drug as determined through in vitro and in vivo experiments. We have also characterized five chemical entities in the drug substance, which provides means for standardization of drug substance and drug product. Based on these findings, a program to develop a safe and effective C. hirsutus-derived phytopharmaceutical drug for the treatment of dengue has been initiated.Author summaryThere is an urgent need to develop a safe and effective drug against dengue, which is a rapidly expanding mosquito-borne viral disease. Half of the world’s population has been estimated to be at risk of contracting this disease and the situation remains grim due to lack of an approved drug. We aimed to develop an ethnopharmacological drug against dengue by exploring traditional Indian medicinal science, Ayurveda. This led us to identify a creeper, Cocculus hirsutus, as a more potent anti-dengue plant than Cissampelos pareira, reported in our earlier published study. The stem part of C. hirsutus was found to be more efficacious in inhibiting the propagation of dengue viruses (DENVs) in cell culture than its aerial part. Hence, we chose to advance aqueous extract of stem of C. hirsutus (AQCH) for further studies. Importantly, AQCH also protected immune-compromised mice from lethal DENV infection, which is suggestive of its potential clinical relevance. We have identified five chemical marker compounds in AQCH to gauge the quality and consistency of extract preparation and its formulation into stable tablets. Based on the findings of this study, we have undertaken the development of a safe and effective C. hirsutus-derived phytopharmaceutical drug for the treatment of dengue.

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Investigational drugs in early development for treating dengue infection

Cited by 22 publications

References 74 publications

A Quinoline Compound Inhibits the Replication of Dengue virus Serotypes 1–4 in Vero Cells

A Quinoline Compound Inhibits the Replication of Dengue virus Serotypes 1–4 in Vero Cells

Structure-Based Design of Antivirals against Envelope Glycoprotein of Dengue Virus

Cocculus hirsutus-derived phytopharmaceutical drug has potent anti-dengue activity

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