scholarly journals Fast and scalable lipid nanoparticle formulation of niclosamide (nano NCM) effectively inhibits SARS-CoV-2 replication in vitro

2020 ◽  
Author(s):  
Guankui Wang ◽  
Hanmant Gaikwad ◽  
Mary K McCarthy ◽  
Mercedes Gonzalez-Juarrero ◽  
Yue Li ◽  
...  

As exemplified by the COVID-19 pandemic, highly infective respiratory viruses can spread rapidly in the population because of lack of effective approaches to control viral replication and spread. Niclosamide (NCM) is an old anthelminthic drug (World Health Organization essential medicine list) with pleiotropic pharmacological activities. Several recent publications demonstrated that NCM has broad antiviral activities and potently inhibits viral replication, including replication of SARS-CoV-2, SARS-CoV, and dengue viruses. Unfortunately, NCM is almost completely insoluble in water, which limits its clinical use. We developed a highly scalable and cost-effective nanoparticle formulation of NCM (nano NCM) using only FDA-approved excipient and demonstrated potency against SARS-CoV-2 infection in cells (Vero E6 and ACE2-expressing lung epithelium cells). Our ultimate goal is to develop the nano NCM formulation for treatment of COVID-19 patients.

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2278 ◽  
Author(s):  
Sahu Henamayee ◽  
Kishore Banik ◽  
Bethsebie Lalduhsaki Sailo ◽  
Bano Shabnam ◽  
Choudhary Harsha ◽  
...  

According to the World Health Organization (WHO), cancer is the second-highest cause of mortality in the world, and it kills nearly 9.6 million people annually. Besides the fatality of the disease, poor prognosis, cost of conventional therapies, and associated side-effects add more burden to patients, post-diagnosis. Therefore, the search for alternatives for the treatment of cancer that are safe, multi-targeted, effective, and cost-effective has compelled us to go back to ancient systems of medicine. Natural herbs and plant formulations are laden with a variety of phytochemicals. One such compound is rhein, which is an anthraquinone derived from the roots of Rheum spp. and Polygonum multiflorum. In ethnomedicine, these plants are used for the treatment of inflammation, osteoarthritis, diabetes, and bacterial and helminthic infections. Increasing evidence suggests that this compound can suppress breast cancer, cervical cancer, colon cancer, lung cancer, ovarian cancer, etc. in both in vitro and in vivo settings. Recent studies have reported that this compound modulates different signaling cascades in cancer cells and can prevent angiogenesis and progression of different types of cancers. The present review highlights the cancer-preventing and therapeutic properties of rhein based on the available literature, which will help to extend further research to establish the chemoprotective and therapeutic roles of rhein compared to other conventional drugs. Future pharmacokinetic and toxicological studies could support this compound as an effective anticancer agent.


2022 ◽  
Vol 2022 ◽  
pp. 1-12
Author(s):  
Arpita Roy ◽  
Ashutosh Anand ◽  
Saksham Garg ◽  
Mohd Shahnawaz Khan ◽  
Sidharth Bhasin ◽  
...  

Cancer is recognized as one of the main causes of mortality worldwide by the World Health Organization. The high cost of currently available cancer therapy and certain limitations of current treatment make it necessary to search for novel, cost-effective, and efficient methods of cancer treatment. Therefore, in the current investigation, sixty-two compounds from five medicinal plants (Tinospora cordifolia, Ocimum tenuiflorum, Podophyllum hexandrum, Andrographis paniculata, and Beta vulgaris) and two proteins that are associated with breast cancer, i.e., HER4/ErbB4 kinase and ERα were selected. Selected compounds were screened using Lipinski’s rule, which resulted in eighteen molecules being ruled out. The remaining forty-four compounds were then taken forward for docking studies followed by molecular dynamics studies of the best screened complexes. Results showed that isocolumbin, isopropylideneandrographolide, and 14-acetylandrographolide were potential lead compounds against the selected breast cancer receptors. Furthermore, in vitro studies are required to confirm the efficacy of the lead compounds.


2020 ◽  
Vol 11 (SPL1) ◽  
pp. 1278-1285
Author(s):  
Mohamed Yafout ◽  
Amine Ousaid ◽  
Ibrahim Sbai El Otmani ◽  
Youssef Khayati ◽  
Amal Ait Haj Said

The new SARS-CoV-2 belonging to the coronaviruses family has caused a pandemic affecting millions of people around the world. This pandemic has been declared by the World Health Organization as an international public health emergency. Although several clinical trials involving a large number of drugs are currently underway, no treatment protocol for COVID-19 has been officially approved so far. Here we demonstrate through a search in the scientific literature that the traditional Moroccan pharmacopoeia, which includes more than 500 medicinal plants, is a fascinating and promising source for the research of natural molecules active against SARS-CoV-2. Multiple in-silico and in-vitro studies showed that some of the medicinal plants used by Moroccans for centuries possess inhibitory activity against SARS-CoV or SARS-CoV-2. These inhibitory activities are achieved through the different molecular mechanisms of virus penetration and replication, or indirectly through stimulation of immunity. Thus, the potential of plants, plant extracts and molecules derived from plants that are traditionally used in Morocco and have activity against SARS-CoV-2, could be explored in the search for a preventive or curative treatment against COVID-19. Furthermore, safe plants or plant extracts that are proven to stimulate immunity could be officially recommended by governments as nutritional supplements.


Author(s):  
Lara Bittmann

On December 31, 2019, WHO was informed of cases of pneumonia of unknown cause in Wuhan City, China. A novel coronavirus was identified as the cause by Chinese authorities on January 7, 2020 and was provisionally named "2019-nCoV". This new Coronavirus causes a clinical picture which has received now the name COVID-19. The virus has spread subsequently worldwide and was explained on the 11th of March, 2020 by the World Health Organization to the pandemic.


2018 ◽  
Vol 24 (10) ◽  
pp. 1138-1147
Author(s):  
Bruno Rivas-Santiago ◽  
Flor Torres-Juarez

Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of World Health Organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the Antimicrobial Peptides (AMPs). These peptides have demonstrated remarkable efficacy to kill mycobacteria in vitro and in vivo in experimental models, nevertheless, these peptides not only have antimicrobial activity but also have a wide variety of functions such as angiogenesis, wound healing, immunomodulation and other well-described roles into the human physiology. Therapeutic strategies for tuberculosis using AMPs must be well thought prior to their clinical use; evaluating comorbidities, family history and risk factors to other diseases, since the wide function of AMPs, they could lead to collateral undesirable effects.


2020 ◽  
Vol 14 (2) ◽  
pp. 134-144 ◽  
Author(s):  
Matthew P. Ameh ◽  
Mamman Mohammed ◽  
Yusuf P. Ofemile ◽  
Magaji G. Mohammed ◽  
Ada Gabriel ◽  
...  

Background: The World Health Organization included snakebite envenomation among Neglected Tropical Diseases in 2017. The importance of natural products from plants is enormous, given that most prescribed drugs originate from plants. Among this is Mucuna pruriens and Mimosa pudica, with many registered patents asserting their health benefits. Objective: This study investigated the in vitro neutralizing effects of Mucuna pruriens seed and Mimosa pudica root extracts on venoms of Naja nigricollis and Bitis arietans. Methods: In mice, the LD50 and phytochemical analysis of M. pruriens and M. pudica plant extracts were carried out prior to the evaluation of their haemolytic and fibrinolytic effect. Their effects on the activities of phospholipase A2 (PLA2) were also assessed. Results: At a concentration of 50 mg/ml, both plant extracts were found to neutralize the fibrinolytic activity of N. nigricollis, but 400 mg/ml was required to neutralize the fibrinolytic activity of B. arietans. In haemolytic studies, 50 mg/ml concentration of M. pruriens extract suppressed haemolysis caused by N. nigricollis venom by 70% but at the same concentration, M. pudica extract reduced haemolysis by 49.4%. M. pruriens, at 50 mg/ml concentration, only inhibited phospholipase A2 activity by 7.7% but higher concentrations up to 400mg/ml had no effect against the venom of N. nigricollis; at 200 mg/ml. M. pudica extract inhibited PLA2 activity by 23%. Conclusion: The results suggest that M. pruriens and M. pudica may be considered as promising antivenom agents for people living in a snake-bite prone environment.


2014 ◽  
Vol 58 (10) ◽  
pp. 5643-5649 ◽  
Author(s):  
Katherine Kay ◽  
Eva Maria Hodel ◽  
Ian M. Hastings

ABSTRACTIt is now World Health Organization (WHO) policy that drug concentrations on day 7 be measured as part of routine assessment in antimalarial drug efficacy trials. The rationale is that this single pharmacological measure serves as a simple and practical predictor of treatment outcome for antimalarial drugs with long half-lives. Herein we review theoretical data and field studies and conclude that the day 7 drug concentration (d7c) actually appears to be a poor predictor of therapeutic outcome. This poor predictive capability combined with the fact that many routine antimalarial trials will have few or no failures means that there appears to be little justification for this WHO recommendation. Pharmacological studies have a huge potential to improve antimalarial dosing, and we propose study designs that use more-focused, sophisticated, and cost-effective ways of generating these data than the mass collection of single d7c concentrations.


2009 ◽  
Vol 6 (4) ◽  
pp. 453-456 ◽  
Author(s):  
Mohammed A. Alshawsh ◽  
Ramzi A. Mothana ◽  
Hassan A. Al-shamahy ◽  
Salah F. Alsllami ◽  
Ulrike Lindequist

Developing countries, where malaria is one of the most prevalent diseases, still rely on traditional medicine as a source for the treatment of this disease. In the present study, six selected plants (Acalypha fruticosa,Azadirachta indica,Cissus rotundifolia,Echium rauwalfii,Dendrosicyos socotranaandBoswellia elongata) commonly used in Yemen by traditional healers for the treatment of malaria as well as other diseases, were collected from different localities of Yemen, dried and extracted with methanol and water successfully. The antiplasmodial activity of the extracts was evaluated against fresh clinical isolates ofPlasmodium falciparum. The selectivity parameters to evaluate the efficacy of these medicinal plants were measured byin vitromicro test (Mark III) according to World Health Organization (WHO) 1996 & WHO 2001 protocols of antimalarial drug tests. Among the investigated 12 extracts, three were found to have significant antiplasmodial activity with IC50values less than 4 µg/ml, namely the water extracts ofA. fruticosa,A. indicaandD. socotrana. Six extracts showed moderate activity with IC50values ranging from 10 to 30 µg/ml and three appeared to be inactive with IC50values more than 30 µg/ml. In addition, preliminary phytochemical screening of the methanolic and aqueous extracts indicated the presence of saponins, tannins, flavonoids, terpenoids, polysaccharides and peptides.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Abd-Elhamid M. Taha

The Safe System (SS) approach to road safety emphasizes safety-by-design through ensuring safe vehicles, road networks, and road users. With a strong motivation from the World Health Organization (WHO), this approach is increasingly adopted worldwide. Considerations in SS, however, are made for the medium-to-long term. Our interest in this work is to complement the approach with a short-to-medium term dynamic assessment of road safety. Toward this end, we introduce a novel, cost-effective Internet of Things (IoT) architecture that facilitates the realization of a robust and dynamic computational core in assessing the safety of a road network and its elements. In doing so, we introduce a new, meaningful, and scalable metric for assessing road safety. We also showcase the use of machine learning in the design of the metric computation core through a novel application of Hidden Markov Models (HMMs). Finally, the impact of the proposed architecture is demonstrated through an application to safety-based route planning.


2002 ◽  
Vol 16 (8) ◽  
pp. 541-545 ◽  
Author(s):  
Naoki Chiba

The issue of whether to screen individuals for Barrett’s esophagus (BE) to prevent esophageal adenocarcinoma (EAC) is highly controversial. Important considerations are that BE is not highly prevalent in the general population and that not many patients with BE develop or die from EAC. Studies that suggest an improved prognosis from surveillance programs are susceptible to lead-time bias. Most of the principles for effective screening, as outlined by the World Health Organization, are not met by endoscopic screening and surveillance protocols. The diagnosis of BE (and dysplasia) is often unclear. Most patients with BE are not identified by screening, and few deaths would be prevented by surveillance. A decision analysis found that the most cost effective screening protocol would be every five years, but the costs associated with prolongation of life are very high, even if a group at high risk for EAC could be identified.


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