In Silico Analysis of the Multi-Targeted Mode of Action of Ivermectin and Related Compounds DOI Creative Commons

Maral Aminpour,

Marco Cannariato, Jordane Preto

et al.

Computation, Journal Year: 2022, Volume and Issue: 10(4), P. 51 - 51

Published: March 25, 2022

Some clinical studies have indicated activity of ivermectin, a macrocyclic lactone, against COVID-19, but biological mechanism initially proposed for this anti-viral effect is not applicable at physiological concentrations. This in silico investigation explores potential modes action ivermectin and 14 related compounds, by which the infectivity morbidity SARS-CoV-2 virus may be limited. Binding affinity computations were performed these agents on several docking sites each models (1) spike glycoprotein virus, (2) CD147 receptor, has been identified as secondary attachment point (3) alpha-7 nicotinic acetylcholine receptor (α7nAChr), an viral penetration neuronal tissue well activation site cholinergic anti-inflammatory pathway controlled vagus nerve. affinities calculated multiple binding compound. Our results indicate high even higher some other compounds evaluated, all three molecular targets. These suggest mechanisms limit stimulate α7nAChr-mediated that could cytokine production immune cells.

Language: Английский

Avermectin Derivatives, Pharmacokinetics, Therapeutic and Toxic Dosages, Mechanism of Action, and Their Biological Effects DOI Creative Commons
Gaber El‐Saber Batiha, Ali Alqahtani, Omotayo B. Ilesanmi

et al.

Pharmaceuticals, Journal Year: 2020, Volume and Issue: 13(8), P. 196 - 196

Published: Aug. 17, 2020

Avermectins are a group of drugs that occurs naturally as product fermenting Streptomyces avermitilis, an actinomycetes, isolated from the soil. Eight different structures, including ivermectin, abamectin, doramectin, eprinomectin, moxidectin, and selamectin, were divided into four major components (A1a, A2a, B1a B2a) minor (A1b, A2b, B1b, B2b). generally used pesticide for treatment pests parasitic worms result their anthelmintic insecticidal properties. Additionally, they possess anticancer, anti-diabetic, antiviral, antifungal, several metabolic disorders. Avermectin works by preventing transmission electrical impulse in muscle nerves invertebrates, amplifying glutamate effects on invertebrates-specific gated chloride channel. has unwanted or reactions, especially when administered indiscriminately, which include respiratory failure, hypotension, coma. The current review examines mechanism actions, biosynthesis, safety, pharmacokinetics, biological toxicity activities avermectins.

Language: Английский

Citations

161
Pharmaceutical compounds used in the COVID-19 pandemic: A review of their presence in water and treatment techniques for their elimination DOI Creative Commons
Carlos Augusto Morales-Paredes, Joan Manuel Rodríguez-Díaz, Nuria Boluda Botella

et al.

The Science of The Total Environment, Journal Year: 2021, Volume and Issue: 814, P. 152691 - 152691

Published: Dec. 30, 2021

During the COVID-19 pandemic, high consumption of antivirals, antibiotics, antiparasitics, antiprotozoals, and glucocorticoids used in treatment this virus has been reported. Conventional systems fail to efficiently remove these contaminants from water, becoming an emerging concern environmental field. Therefore, objective present work is address current state literature on presence removal processes drugs water bodies. It was found that concentration most increased during pandemic Before Azithromycin concentrations surface waters were reported be order 4.3 ng L

Language: Английский

Citations

160
Ivermectin as a potential drug for treatment of COVID-19: an in-sync review with clinical and computational attributes DOI Creative Commons
Harpinder Kaur, Nishant Shekhar, Saurabh Sharma

et al.

Pharmacological Reports, Journal Year: 2021, Volume and Issue: 73(3), P. 736 - 749

Published: Jan. 3, 2021

COVID-19 cases are on surge; however, there is no efficient treatment or vaccine that can be used for its management. Numerous clinical trials being reviewed use of different drugs, biologics, and vaccines in COVID-19. A much empirical approach will to repurpose existing drugs which pharmacokinetic safety data available, because this facilitate the process drug development. The article discusses evidence available Ivermectin, an anti-parasitic with antiviral properties, rational review was carried out utilizing their clinically significant attributes. more thorough understanding met by virtual embodiment structure realizable viral targets using artificial intelligence (AI)-based molecular dynamics (MD)-simulation-based study. Certain studies have highlighted significance ivermectin COVID-19; it requires evidences from Randomised Controlled Trials (RCTs) dose- response support use. In silico-based analysis ivermectin's interaction specificity AI classical mechanics simulation-based methods indicates positive protein targets, leading SARS-CoV 2 N-protein NTD (nucleocapsid N-terminal domain).

Language: Английский

Citations

87
Macrolides: From Toxins to Therapeutics DOI Creative Commons
Kiersten D. Lenz, Katja E. Klosterman, Harshini Mukundan

et al.

Toxins, Journal Year: 2021, Volume and Issue: 13(5), P. 347 - 347

Published: May 12, 2021

Macrolides are a diverse class of hydrophobic compounds characterized by macrocyclic lactone ring and distinguished variable side chains/groups. Some the most well macrolides toxins produced marine bacteria, sea sponges, other species. Many macrolide act as biomimetic molecules to natural actin-binding proteins, affecting actin polymerization, while on different cytoskeletal components. The disruption processes affects cell motility cytokinesis, can result in cellular death. While many toxic nature, others have been shown display therapeutic properties. Indeed, some known antibiotic compounds, including erythromycin, macrolides. In addition properties, antiviral, antiparasitic, antifungal, immunosuppressive actions. Here, we review each functional for their common structures, mechanisms action, pharmacology, human targets.

Language: Английский

Citations

85
Misleading clinical evidence and systematic reviews on ivermectin for COVID-19 DOI Open Access
Luis Garegnani, Eva Madrid, Nicolás Meza

et al.

BMJ evidence-based medicine, Journal Year: 2021, Volume and Issue: 27(3), P. 156 - 158

Published: April 22, 2021

Background:

Avascular necrosis (AN) is a disabling disease affecting predominantly young men. It steadily progresses to secondary osteoarthritis. The rate of disability high, because hip joint most commonly affected by AN; moreover, the bilateral involvement also high. key event in pathogenesis AN circulation disorder which results ischemia and, furthermore, death bone tissue. Nowadays data about lipid metabolism patients with AN. Besides, there contradictory role homocysteine risk cardiovascular events. Based on these, it topical investigate and endothelial function

Objectives:

aim present study was different stages order find factors for incidence progression this disease.

Methods:

We recruited 41 femoral head or condyles aged 51 (35-64) years, 56,1% (n=23) were male. inclusion criteria diagnosis confirmed X-Ray, CT MRI. exclusion were: traumatic AN, Legg-Calve-Pertes disease, connective tissue systemic diseases. Also we divided into subgroups early (39% (n=16)) late (61,0% (n=25)) Patients control group (n=32) comparable age gender. proceeded using non-parametric descriptive statistics. evaluated following parameters: homocysteine, total cholesterol, high-density lipoprotein low-density very cholesterol ratio, apolipoprotein A1, B.

Results:

In observed higher level (12,119 (7,771-14,38) vs. 7,911 (6,612-10,54) mcmol/l, p=0,05). are consistent that homocyseine associated events (1). There literature elevated lower levels vitamin B12 folic acid. Thus, interpretation homocystene significance more reliable association acid levels. Also, HDLP-C than pate (1,55 (1,31-1,57) 1,23 (1,04-1,36) mmol/l, р=0,04). can be interpreted as protective factor against contralateral patients. obtained existing lowers

Conclusion:

indicate significant dyslypidemia context vascular theory.

References:

[1]Steven G. Chrysant & George S. (2018) current status disease: mini review, Expert Review Cardiovascular Therapy, 16:8, 559-565, DOI: 10.1080/14779072.2018.1497974. [2]Narayanan, A., Khanchandani, P., Borkar, R.M. et al. Necrosis Femoral Head: A Metabolomic, Biophysical, Biochemical, Electron Microscopic Histopathological Characterization. Sci Rep 7, 10721 (2017). https://doi.org/10.1038/.

Disclosure Interests:

Katsiarina Gudkevich: None declared, Natalia Martusevich Shareholder of: k, Elena Dashkevich: declared

Language: Английский

Citations

79
Ivermectin: an award-winning drug with expected antiviral activity against COVID-19 DOI Open Access
Fábio Rocha Formiga,

Roger LeBlanc,

Juliana de Souza Rebouças

et al.

Journal of Controlled Release, Journal Year: 2020, Volume and Issue: 329, P. 758 - 761

Published: Oct. 7, 2020

Language: Английский

Citations

78
Effects of Ivermectin in Patients With COVID-19: A Multicenter, Double-blind, Randomized, Controlled Clinical Trial DOI Creative Commons
Leila Shahbaznejad, Alireza Davoudi, Gohar Eslami

et al.

Clinical Therapeutics, Journal Year: 2021, Volume and Issue: 43(6), P. 1007 - 1019

Published: May 6, 2021

Language: Английский

Citations

71
Exploring the Binding Efficacy of Ivermectin Against the Key Proteins of SARS-CoV-2 Pathogenesis: an in silico Approach DOI
Abhigyan Choudhury, Nabarun Chandra Das, Ritwik Patra

et al.

Future Virology, Journal Year: 2021, Volume and Issue: 16(4), P. 277 - 291

Published: March 25, 2021

Aim: COVID-19 is currently the biggest threat to mankind. Recently, ivermectin (a US FDA-approved antiparasitic drug) has been explored as an anti-SARS-CoV-2 agent. Herein, we have studied possible mechanism of action using in silico approaches. Materials & methods: Interaction against key proteins involved SARS-CoV-2 pathogenesis were investigated through molecular docking and dynamic simulation. Results: Ivermectin was found a blocker viral replicase, protease human TMPRSS2, which could be biophysical basis behind its antiviral efficiency. The ADMET profile on par with used anticorona drugs such hydroxychloroquine remdesivir. Conclusion: Our study enlightens candidature effective drug for treating COVID-19.

Language: Английский

Citations

69
Therapeutics for COVID-19 and post COVID-19 complications: An update DOI Creative Commons

Debdoot Basu,

Vivek P. Chavda,

Anita A. Mehta

et al.

Current Research in Pharmacology and Drug Discovery, Journal Year: 2022, Volume and Issue: 3, P. 100086 - 100086

Published: Jan. 1, 2022

Since its inception in late December 2020 China, novel coronavirus has affected the global socio-economic aspect. Currently, world is seeking safe and effective treatment measures against COVID-19 to eradicate it. Many established drug molecules are tested SARS-CoV-2 as a part of repurposing where some proved for symptomatic relief while ineffective. Drug practical strategy rapidly developing antiviral agents. drugs presently being repurposed utilizing basic understanding disease pathogenesis pharmacodynamics, well computational methods. In present situation, could be viewed new option COVID-19. Several biologics engineered under different stages clinical development. A few products approved by USFDA emergency use covid management. Due continuous mutation, many vaccines not much efficacious render individual immune opportunistic infection mutants. Hence, there strong need cogent therapeutic agent this review, consolidated summary developments depicted along with an overview management post complications.

Language: Английский

Citations

69
The mechanisms of action of ivermectin against SARS-CoV-2—an extensive review DOI Open Access
Asiya Kamber Zaidi, Puya Dehgani‐Mobaraki

The Journal of Antibiotics, Journal Year: 2021, Volume and Issue: 75(2), P. 60 - 71

Published: Dec. 21, 2021

Language: Английский

Citations

62