Natural Products and Potential Therapeutic Intervention for COVID-19

2021 ◽  
Author(s):  
Fengyu Zhang
Keyword(s):  
Natural Products ◽  
Drug Targets ◽  
Randomized Clinical Trials ◽  
Preventive Intervention ◽  
Pharmacokinetic Parameters ◽  
Potential Efficacy ◽  
Effective Prophylaxis ◽  
Parasite Infections ◽  
Eukaryotic Organisms ◽  
Potential Therapeutic Intervention

The coronavirus disease 19 (COVID-19) caused pandemic is still prevailing, but few approved medications are available. While the vaccinations have begun in some areas, it is of concern how the virus mutations will affect the vaccine effectiveness in populations. Various natural products exhibit good pharmacological properties of antiviral, antioxidant, and anti-inflammatory activities that may offer preventive intervention benefits. In addition to that, adequate essential minerals and trace elements (e.g., selenium and zinc) are required for healthy immune function; many natural products from prokaryotic and eukaryotic organisms can be potential drug targets. Among them are plant extracts traditionally used for antiviral and parasite infections. Two phytochemicals, hesperidin, and sulforaphane might be the most promising candidates for effective prophylaxis and mitigating disease severity. Therefore, they deserve a further study of their antiviral mechanisms of action then move to randomized clinical trials to determine appropriate dosing, pharmacokinetic parameters, and their potential efficacy and safety in humans.

scholarly journals Natural Products in Clinical Trials

Proceedings ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 32
Author(s):  
YERER
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Alternative Medicine ◽  
Complementary And Alternative Medicine ◽  
Randomized Clinical Trials ◽  
Ginseng Root ◽  
Pharmacokinetic Parameters ◽  
Number Of Patients ◽  
Cancer Types ◽  
Complementary And Alternative

Herbal medicines are complementary and alternative medicine that is used not only in the treatment of cancer and cancer-related conditions, but also to improve the side effects of anticancer therapies. The use of so‐called alternative medicine has increased over the past 10 years, and the use of herbal preparations in clinical trials are growing. Complementary therapies are used by a large number of patients with cancer, particularly those with progressive disease or who have undergone multiple treatments. In 1998, spurred by rising interest in the use of complementary and alternative medicine (CAM) for cancer patients, the National Cancer Institute (NCI) created the Office of Cancer Complementary and Alternative Medicine (OCCAM) and has supported OCCAM with more than $100 million annually since 2005. In the clinical trials official website there are 540 studies were found to be held by extracts whereas 78 studies were found to be held by CAM and 49 studies with marine products by December 2019. The green tea, grape seed, pomegranate, wheat germ, ginger, ginseng root, broccoli sprout, green coffee, Red Reishi, Iscador Q, mistletoe were the most common herbal extracts used in Randomized Clinical Trials (RCT). Curcumin, resveratrol, epigallocathechin gallate, osthole, fiscetin are the samples which are the most common used natural products in RCTs in several cancer types. Prostate, colorectal, breast, lung, head and neck cancers were the most common cancer types where these CAM and natural products were used in RCTs. Increasingly, many researchers have focused their efforts on the potential use of CAMs and natural products and have reevaluated earlier epidemiologic data and initiated clinical trials to determine their potential efficacy as cancer therapy however the pharmacokinetic parameters of these products still need to be widely evaluated by identifying more clinical evidence to be able to use in patients.

scholarly journals Pharmacokinetics of intramuscularly administered aminosidine in healthy subjects.

1997 ◽  
Vol 41 (5) ◽  
pp. 982-986 ◽  
Author(s):  
T P Kanyok ◽  
A D Killian ◽  
K A Rodvold ◽  
L H Danziger
Keyword(s):  
Healthy Subjects ◽  
Randomized Clinical Trials ◽  
Elimination Rate ◽  
Pharmacokinetic Parameters ◽  
Multiple Drug ◽  
Time Data ◽  
Time Curve ◽  
First Order ◽  
Significant Difference

Aminosidine is an older, broad-spectrum aminoglycoside antibiotic that has been shown to be effective in in vitro and animal models against multiple-drug-resistant tuberculosis and the Mycobacterium avium complex. The objective of this randomized, parallel trial was to characterize the single-dose pharmacokinetics of aminosidine sulfate in healthy subjects (eight males, eight females). Sixteen adults (mean [+/- standard deviation] age, 27.6 +/- 5.6 years) were randomly allocated to receive a single, intramuscular aminosidine sulfate injection at a dose of 12 or 15 mg/kg of body weight. Serial plasma and urine samples were collected over a 24-h period and used to determine aminosidine concentrations by high-performance liquid chromatographic assay. A one-compartment model with first-order input, first-order output, and a lag time (Tlag) and with a weighting factor of 1/y2 best described the data. Compartmental and noncompartmental pharmacokinetic parameters were estimated with the microcomputer program WinNonlin. One subject was not included (15-mg/kg group) because of the lack of sampling time data. On average, subjects attained peak concentrations of 22.4 +/- 3.2 microg/ml at 1.34 +/- 0.45 h. All subjects had plasma aminosidine concentrations below 2 microg/ml at 12 h, and all but two subjects (one in each dosing group) had undetectable plasma aminosidine concentrations at 24 h. The dose-adjusted area under the concentration-time curve from 0 h to infinity of aminosidine was identical for the 12- and 15-mg/kg groups (9.29 +/- 1.5 versus 9.29 +/- 2.2 microg x h/ml per mg/kg; P = 0.998). Similarly, no significant differences (P > 0.05) were observed between dosing groups for peak aminosidine concentration in plasma, time to peak aminosidine concentration in plasma, Tlag, apparent clearance, renal clearance, elimination rate constant, and elimination half-life. A significant difference was observed for the volume of distribution (0.35 versus 0.41 liters/kg; P = 0.037) between the 12 and 15 mg/kg dosing groups. Now that comparable pharmacokinetic profiles between dosing groups have been demonstrated, therapeutic equivalency testing via in vitro pharmacokinetic and pharmacodynamic modelling and randomized clinical trials in humans should be conducted.

scholarly journals Multiplexed screening of thousands of natural products for protein-ligand binding in native mass spectrometry

2021 ◽  
Author(s):  
Giang Nguyen ◽  
Jack Bennett ◽  
Sherrie Liu ◽  
Sarah Hancock ◽  
Daniel Winter ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Natural Products ◽  
Drug Discovery ◽  
Small Molecules ◽  
Natural Product ◽  
Drug Targets ◽  
Structural Diversity ◽  
Native Mass Spectrometry ◽  
Protein Targets ◽  
Rapid Measurement

The structural diversity of natural products offers unique opportunities for drug discovery, but challenges associated with their isolation and screening can hinder the identification of drug-like molecules from complex natural product extracts. Here we introduce a mass spectrometry-based approach that integrates untargeted metabolomics with multistage, high-resolution native mass spectrometry to rapidly identify natural products that bind to therapeutically relevant protein targets. By directly screening crude natural product extracts containing thousands of drug-like small molecules using a single, rapid measurement, novel natural product ligands of human drug targets could be identified without fractionation. This method should significantly increase the efficiency of target-based natural product drug discovery workflows.

scholarly journals Targeting tRNA-Synthetase Interactions towards Novel Therapeutic Discovery Against Eukaryotic Pathogens

2019 ◽  
Author(s):  
Paul Kelly ◽  
Fatemeh Hadi-Nezhad ◽  
Dennis Liu ◽  
Travis J. Lawrence ◽  
Roger G. Linington ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Broad Spectrum ◽  
Marine Natural Products ◽  
Drug Targets ◽  
Leishmania Major ◽  
Trna Synthetase ◽  
Cross Reactivity ◽  
Protein Synthesis Inhibitors ◽  
Macromolecular Interactions

AbstractThe development of chemotherapies against eukaryotic pathogens is especially challenging because of both the evolutionary conservation of drug targets between host and parasite, and the evolution of strain-dependent drug resistance. There is a strong need for new nontoxic drugs with broad-spectrum activity against trypanosome parasites such as Leishmania and Trypanosoma. A relatively untested approach is to target macromolecular interactions in parasites rather than small molecular interactions, under the hypothesis that the features specifying macromolecular interactions diverge more rapidly through coevolution. We computed tRNA Class-Informative Features in humans and eight clades of trypanosomes, identifying parasite-specific informative features (including base-pairs and base mis-pairs) that are broadly conserved over approximately 250 million years of trypanosome evolution. Validating these observations, we demonstrated biochemically that tRNA:aminoacyl-tRNA synthetase interactions are a promising target for anti-trypanosomal drug discovery. From a marine natural products extract library, we identified several fractions with inhibitory activity toward Leishmania major alanyl-tRNA synthetase (AlaRS) but no activity against the human homolog. These marine natural products extracts showed cross-reactivity towards Trypanosoma cruzi AlaRS indicating the broad-spectrum potential of our network predictions. These findings support a systems biology model in which combination chemotherapies that target multiple tRNA-synthetase interactions should be comparatively less prone to the emergence of resistance than conventional single drug therapies.Author SummaryTrypanosome parasites pose a significant health risk worldwide. Conventional drug development strategies have proven challenging given the high conservation between humans and pathogens, with off-target toxicity being a common problem. Protein synthesis inhibitors have historically been an attractive target for antimicrobial discovery against bacteria, and more recently for eukaryotic pathogens. Here we propose that exploiting pathogen-specific tRNA-synthetase interactions offers the potential for highly targeted drug discovery. To this end, we improved tRNA gene annotations in trypanosome genomes, identified functionally informative trypanosome-specific tRNA features, and showed that these features are highly conserved over approximately 250 million years of trypanosome evolution. Highlighting the species-specific and broad-spectrum potential of our approach, we identified natural product inhibitors against the parasite translational machinery that have no effect on the homologous human enzyme.

scholarly journals Natural product drug discovery in the artificial intelligence era

2022 ◽  
Author(s):  
Fernanda I Saldivar-Gonzalez ◽  
Victor Daniel Aldas-Bulos ◽  
José Luis Medina-Franco ◽  
Fabien Plisson
Keyword(s):  
Artificial Intelligence ◽  
Natural Products ◽  
Drug Discovery ◽  
Natural Product ◽  
Drug Targets ◽  
Structural Diversity ◽  
Protein Drug ◽  
Privileged Structures

Natural products (NPs) are primarily recognized as privileged structures to interact with protein drug targets. Their unique characteristics and structural diversity continue to marvel scientists for developing NP-inspired medicines, even...

scholarly journals Drug Discovery on Natural Products: From Ion Channels to nAChRs, from Nature to Libraries, from Analytics to Assays

2019 ◽  
Vol 24 (3) ◽  
pp. 362-385 ◽  
Author(s):  
Reka A. Otvos ◽  
Kristina B. M. Still ◽  
Govert W. Somsen ◽  
August B. Smit ◽  
Jeroen Kool
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Ion Channels ◽  
Ion Channel ◽  
Bioactive Compounds ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Drug Targets ◽  
Α7 Nachr ◽  
Analytical Approaches

Natural extracts are complex mixtures that may be rich in useful bioactive compounds and therefore are attractive sources for new leads in drug discovery. This review describes drug discovery from natural products and in explaining this process puts the focus on ion-channel drug discovery. In particular, the identification of bioactives from natural products targeting nicotinic acetylcholine receptors (nAChRs) and serotonin type 3 receptors (5-HT3Rs) is discussed. The review is divided into three parts: “Targets,” “Sources,” and “Approaches.” The “Targets” part will discuss the importance of ion-channel drug targets in general, and the α7-nAChR and 5-HT3Rs in particular. The “Sources” part will discuss the relevance for drug discovery of finding bioactive compounds from various natural sources such as venoms and plant extracts. The “Approaches” part will give an overview of classical and new analytical approaches that are used for the identification of new bioactive compounds with the focus on targeting ion channels. In addition, a selected overview is given of traditional venom-based drug discovery approaches and of diverse hyphenated analytical systems used for screening complex bioactive mixtures including venoms.

Evidence and the main adverse effects regarding drug therapies in the war against COVID-19

2020 ◽  
Vol 27 ◽  
Author(s):  
Mauricio Mora-Ramírez ◽  
Paulina Melgoza-Hernández ◽  
Sebastian Eduardo Toledo-Ramírez ◽  
Juan Manuel Mejía Aranguré
Keyword(s):  
Adverse Effects ◽  
Drug Targets ◽  
English Language ◽  
Randomized Clinical Trials ◽  
Case Reports ◽  
Case Series ◽  
Pharmacological Therapy ◽  
Rapid Review ◽  
Definitive Therapy ◽  
Potential Drug Targets

Background: Nowadays, the breakthrough of COVID-19 pandemic around the world is the biggest health challenge for the clinicians, and it represents an unexpected effort to identify effective treatment for those patients. No proven definitive therapies for this infection currently exist. Unfortunately, the infected patients increased in an alarming way every day, faster than medical evidence. At present, the expanding knowledge regarding SARS-COV-2 virology provides several potential drug targets. Objective: Therefore, clinicians need a rapid review and guideline about the main adverse effects regarding the most prescribed drugs and, specifically, the efficacy and potential risk of each pharmacological therapy, during hospital care. Methods: The articles review was performed using PubMed to identify relevant papers in English language reported through July 20th, 2020; a second review was performed using Web of Science until August 28th. Due to the lack of randomized clinical trials, we included case reports, case series, and reviews. We found 1606 total articles related. The authors independently reviewed the titles and abstracts for inclusion. Conclusion: At present, despite the enormous medical effort for publishing several trials or case reports, we have not yet discovered a definitive therapy against the COVID-19 infection. This brief review aims to prompt identification of risk factors and main adverse effects in a systematic view related to therapy with partial evidence proposed to date.

Multiplexed screening of thousands of natural products for protein-ligand binding in native mass spectrometry

2021 ◽  
Author(s):  
Giang Nguyen ◽  
Jack Bennett ◽  
Sherrie Liu ◽  
Sarah Hancock ◽  
Daniel Winter ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Natural Products ◽  
Drug Discovery ◽  
Small Molecules ◽  
Natural Product ◽  
Drug Targets ◽  
Structural Diversity ◽  
Native Mass Spectrometry ◽  
Protein Targets ◽  
Rapid Measurement

The structural diversity of natural products offers unique opportunities for drug discovery, but challenges associated with their isolation and screening can hinder the identification of drug-like molecules from complex natural product extracts. Here we introduce a mass spectrometry-based approach that integrates untargeted metabolomics with multistage, high-resolution native mass spectrometry to rapidly identify natural products that bind to therapeutically relevant protein targets. By directly screening crude natural product extracts containing thousands of drug-like small molecules using a single, rapid measurement, novel natural product ligands of human drug targets could be identified without fractionation. This method should significantly increase the efficiency of target-based natural product drug discovery workflows.

Binding of anti-Trypanosoma natural products from African flora against selected drug targets: a docking study

2017 ◽  
Vol 26 (3) ◽  
pp. 562-579 ◽  
Author(s):  
Akachukwu Ibezim ◽  
Biplab Debnath ◽  
Fidele Ntie-Kang ◽  
Chika John Mbah ◽  
Ngozi Justina Nwodo
Keyword(s):  
Natural Products ◽  
Drug Targets ◽  
Docking Study ◽  
African Flora
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