Clinical safety and pharmacokinetic evaluation of aqueous extract of Cocculus hirsutus, an anti-viral phytopharmacetical drug as a potential for the treatment of dengue and COVID-19

Dar, Sajad Khaliq; Kumar, Sanjeev; Maiti, Sovan; Dhawan, Shilpi; Joglekar, Sadhna; Arora, Upasana; Kalra, Rinku; Madan, Sumit; Lal, Altaf A.; Singamaneni, Venugopal; Gupta, Prasoon; Nandi, Utpal; Singh, Deepika; Khuroo, Arshad

doi:10.1016/j.heliyon.2022.e09416

Cited by 5 publications

(3 citation statements)

References 14 publications

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“…Out of these chemical compounds, only Sinococuline exhibited anti-DENV inhibitory property when evaluated in vitro. Furthermore, the AQCH phytopharmaceutical substance was made and evaluated clinically which was found to be very safe for human use 41 .…”

Section: Discussionmentioning

confidence: 99%

Sinococuline, a bioactive compound of Cocculus hirsutus has potent anti-dengue activity

Ahuja

Beesetti

Garg

et al. 2023

Sci Rep

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Dengue virus (DENV) infection has increased worldwide, with over 400 million infections annually, and has become a serious public health concern. Several drug candidates, new and repurposed, have failed to meet the primary efficacy endpoints. We have recently shown that Aqueous Extract of the stem of Cocculus hirsutus (AQCH) was effective in vitro and in vivo against DENV and was safe in humans. We now report that an active ingredient of AQCH, Sinococuline, protects against the antibody-mediated secondary-DENV infection in the AG129 mouse model. DENV infection markers were assessed, viz. serum viremia and vital organs pathologies-viral load, proinflammatory cytokines and intestinal vascular leakage. The treatment with Sinococuline at 2.0 mg/kg/day; BID (twice a day), was the most effective in protecting the severely DENV-infected AG129 mice. Also, this dose effectively reduced serum viremia and tissue-viral load and inhibited the elevated expression levels of proinflammatory cytokines (TNF-α and IL-6) in several vital organs. Based on these findings, it could be explored further for pre-clinical and clinical developments for the treatment of dengue.

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Section: Discussionmentioning

confidence: 99%

Sinococuline, a bioactive compound of Cocculus hirsutus has potent anti-dengue activity

Ahuja

Beesetti

Garg

et al. 2023

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

'Sinococuline, a bioactive compound of Cocculus hirsutus has potent anti-dengue activity’

Ahuja

Beesetti

Garg

et al. 2022

Preprint

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Dengue Virus (DENV) infection has increased worldwide, with over 400 million infections annually, and has become a serious public health concern. Several drug candidates, new and repurposed, have failed to meet the primary efficacy endpoints. We have recently shown that Aqueous Extract of the stem of Cocculus hirsutus (AQCH) was effective in vitro and in vivo against DENV and was safe in humans. We now report that an active ingredient of AQCH, Sinococuline, protects against the antibody-mediated secondary-DENV infection in the AG129 mouse model. DENV infection markers were assessed, viz. serum viremia and vital organs pathologies- viral load, proinflammatory cytokines and intestinal vascular leakage. The treatment with Sinococuline at 2.0 mg/kg/dose, twice a day (BID), was the most effective in protecting the severely DENV-infected AG129 mice. Also, this dose effectively reduced serum viremia and tissue-viral load and inhibited the elevated expression levels of proinflammatory cytokines (TNF-α & IL-6) in several vital organs. Based on these findings, it could be explored further for pre-clinical and clinical developments for the treatment of dengue.

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“…The vast majority of clinical trials do not evaluate anti-infective drugs registered for human use for an indication other than the NTD for which they are trialed and thus do not meet our inclusion criteria. Given the extent of research with traditional medicines which does not meet our inclusion criteria ( Cocculus hirsutus extracts [ 137 , 138 ], C. papaya extracts [ 139 – 141 ], Ganghuo Kanggan decoction (GHKGD) [ 142 ], Eupatorium perfoliatum [ 143 , 144 ]) we provided short summaries in Additional file 1 .…”

Section: Ntds Targeted For Controlmentioning

confidence: 99%

The pipeline for drugs for control and elimination of neglected tropical diseases: 2. Oral anti-infective drugs and drug combinations for off-label use

Pfarr,

Krome,

Al-Obaidi

et al. 2023

Parasites Vectors

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In its ‘Road map for neglected tropical diseases 2021–2030’, the World Health Organization outlined its targets for control and elimination of neglected tropical diseases (NTDs) and research needed to achieve them. For many NTDs, this includes research for new treatment options for case management and/or preventive chemotherapy. Our review of small-molecule anti-infective drugs recently approved by a stringent regulatory authority (SRA) or in at least Phase 2 clinical development for regulatory approval showed that this pipeline cannot deliver all new treatments needed. WHO guidelines and country policies show that drugs may be recommended for control and elimination for NTDs for which they are not SRA approved (i.e. for ‘off-label’ use) if efficacy and safety data for the relevant NTD are considered sufficient by WHO and country authorities. Here, we are providing an overview of clinical research in the past 10 years evaluating the anti-infective efficacy of oral small-molecule drugs for NTD(s) for which they are neither SRA approved, nor included in current WHO strategies nor, considering the research sponsors, likely to be registered with a SRA for that NTD, if found to be effective and safe. No such research has been done for yaws, guinea worm, Trypanosoma brucei gambiense human African trypanosomiasis (HAT), rabies, trachoma, visceral leishmaniasis, mycetoma, T. b. rhodesiense HAT, echinococcosis, taeniasis/cysticercosis or scabies. Oral drugs evaluated include sparfloxacin and acedapsone for leprosy; rifampicin, rifapentin and moxifloxacin for onchocerciasis; imatinib and levamisole for loiasis; itraconazole, fluconazole, ketoconazole, posaconazole, ravuconazole and disulfiram for Chagas disease, doxycycline and rifampicin for lymphatic filariasis; arterolane, piperaquine, artesunate, artemether, lumefantrine and mefloquine for schistosomiasis; ivermectin, tribendimidine, pyrantel, oxantel and nitazoxanide for soil-transmitted helminths including strongyloidiasis; chloroquine, ivermectin, balapiravir, ribavirin, celgosivir, UV-4B, ivermectin and doxycycline for dengue; streptomycin, amoxicillin, clavulanate for Buruli ulcer; fluconazole and isavuconazonium for mycoses; clarithromycin and dapsone for cutaneous leishmaniasis; and tribendimidine, albendazole, mebendazole and nitazoxanide for foodborne trematodiasis. Additional paths to identification of new treatment options are needed. One promising path is exploitation of the worldwide experience with ‘off-label’ treatment of diseases with insufficient treatment options as pursued by the ‘CURE ID’ initiative. Graphical abstract

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Clinical safety and pharmacokinetic evaluation of aqueous extract of Cocculus hirsutus, an anti-viral phytopharmacetical drug as a potential for the treatment of dengue and COVID-19

Cited by 5 publications

References 14 publications

Sinococuline, a bioactive compound of Cocculus hirsutus has potent anti-dengue activity

Sinococuline, a bioactive compound of Cocculus hirsutus has potent anti-dengue activity

'Sinococuline, a bioactive compound of Cocculus hirsutus has potent anti-dengue activity’

The pipeline for drugs for control and elimination of neglected tropical diseases: 2. Oral anti-infective drugs and drug combinations for off-label use

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