scholarly journals Pharmacological Advances of Chloroquine and Hydroxychloroquine: From Antimalarials to Investigative Therapies in COVID-19

2020 ◽  
Vol 15 (9) ◽  
pp. 1934578X2095364
Author(s):  
Yang Song ◽  
Elise Fields
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Adverse Effects ◽  
Viral Infection ◽  
Therapeutic Potential ◽  
Pharmacological Activities ◽  
Pharmaceutical Applications ◽  
Natural Alkaloid ◽  
Derivatives Of ◽  
Existing Chemicals

During the coronavirus disease 2019 (COVID-19) pandemic, numerous existing chemicals have been screened for antiviral potential against the emerging coronavirus severe acute respiratory syndrome coronavirus 2. Chloroquine and hydroxychloroquine, after exhibiting potent in vitro efficacy, have gained tremendous attention. Both therapeutics are derivatives of natural alkaloid quinine and were first synthesized to treat malaria. Thereafter, the pharmaceutical applications of the agents have expanded to many new areas. In this article, the medicinal history and pharmacological activities of chloroquine and hydroxychloroquine are summarized. Antimalarial, anti-inflammatory, antitumor, antiviral properties, and therapeutic potential in the emerging viral infection COVID-19 are discussed. Pharmacokinetics, adverse effects, and toxicities are reviewed.

scholarly journals Identification of Anti-Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Oxysterol Derivatives In Vitro

2021 ◽  
Vol 22 (6) ◽  
pp. 3163
Author(s):  
Hirofumi Ohashi ◽  
Feng Wang ◽  
Frank Stappenbeck ◽  
Kana Tsuchimoto ◽  
Chisa Kobayashi ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Viral Replication ◽  
Cultured Cells ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Membrane Vesicles ◽  
Drug Candidates ◽  
Increased Risk ◽  
Derivatives Of

The development of effective antiviral drugs targeting the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is urgently needed to combat the coronavirus disease 2019 (COVID-19). We have previously studied the use of semi-synthetic derivatives of oxysterols, oxidized derivatives of cholesterol as drug candidates for the inhibition of cancer, fibrosis, and bone regeneration. In this study, we screened a panel of naturally occurring and semi-synthetic oxysterols for anti-SARS-CoV-2 activity using a cell culture infection assay. We show that the natural oxysterols, 7-ketocholesterol, 22(R)-hydroxycholesterol, 24(S)-hydroxycholesterol, and 27-hydroxycholesterol, substantially inhibited SARS-CoV-2 propagation in cultured cells. Among semi-synthetic oxysterols, Oxy210 and Oxy232 displayed more robust anti-SARS-CoV-2 activities, reducing viral replication more than 90% at 10 μM and 99% at 15 μM, respectively. When orally administered in mice, peak plasma concentrations of Oxy210 fell into a therapeutically relevant range (19 μM), based on the dose-dependent curve for antiviral activity in our cell-based assay. Mechanistic studies suggest that Oxy210 reduced replication of SARS-CoV-2 by disrupting the formation of double-membrane vesicles (DMVs); intracellular membrane compartments associated with viral replication. Our study warrants further evaluation of Oxy210 and Oxy232 as a safe and reliable oral medication, which could help protect vulnerable populations with increased risk of developing COVID-19.

scholarly journals The 3a protein of severe acute respiratory syndrome-associated coronavirus induces apoptosis in Vero E6 cells

2005 ◽  
Vol 86 (7) ◽  
pp. 1921-1930 ◽  
Author(s):  
Patrick T. W. Law ◽  
Chi-Hang Wong ◽  
Thomas C. C. Au ◽  
Chi-Pang Chuck ◽  
Siu-Kai Kong ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Severe Acute Respiratory Syndrome ◽  
Viral Infection ◽  
Viral Protein ◽  
Host Response ◽  
Transmembrane Protein ◽  
Chromatin Condensation ◽  
Aetiological Agent ◽  
First Case

An outbreak of severe acute respiratory syndrome (SARS) occurred in China and the first case emerged in mid-November 2002. The aetiological agent of this disease was found to be a previously unknown coronavirus, SARS-associated coronavirus (SARS-CoV). The detailed pathology of SARS-CoV infection and the host response to the viral infection are still not known. The 3a gene encodes a non-structural viral protein, which is predicted to be a transmembrane protein. In this study, it was shown that the 3a protein was expressed in the lungs and intestinal tissues of SARS patients and that the protein localized to the endoplasmic reticulum in 3a-transfected monkey kidney Vero E6 cells. In vitro experiments of chromatin condensation and DNA fragmentation suggested that the 3a protein may trigger apoptosis. These data showed that overexpression of a single SARS-CoV protein can induce apoptosis in vitro.

scholarly journals Uncontrolled mass use of hydroxychloroquine

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 396-398
Author(s):  
Tugolbai Tagaev ◽  
Sagynali Mamatov ◽  
Farida Imanalieva ◽  
Vityala Yethindra ◽  
Altynai Zhumabekova ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Therapeutic Drug Monitoring ◽  
Severe Acute Respiratory Syndrome ◽  
Adverse Effects ◽  
Medical Advice ◽  
Therapeutic Drug ◽  
Converting Enzyme ◽  
Weak Base ◽  
Angiotensin Converting Enzyme 2

Hydroxychloroquine (HCQ) has previously been shown to inhibit coronavirus replication in vitro. But antiviral properties mechanisms are not well known, HCQ is a weak base that accumulates in lysosomes, modifies their pH, and interferes with some enzymes. In the lack of confirmed efficacy, the initial potential risk is not to expose patients to adverse effects. However, results from preliminary clinical studies have drawn inconclusive results regarding the efficacy of HCQ in coronavirus disease 2019 (COVID-19), due to several important weaknesses in research methodologies. Hypokalemia often occurs in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), possibly due to the particular tropism of SARS-CoV-2 with regard to Angiotensin-converting enzyme 2 (ACE2). The wide use of HCQ, even against medical advice, will show an impact on ongoing clinical trials. It is important that we can recruite COVID-19 patients in these research studies to generate appropriate data regarding drugs that show promising efficacy against COVID-19. Currently, only doctors should be allowed to prescribe HCQ, and treatment should be confined to hospital settings, with proper cardiac and therapeutic drug monitoring.

scholarly journals Therapeutic Potential Of Multifunctional Derivatives Of Cholinesterase Inhibitors

2020 ◽  
Vol 19 ◽  
Author(s):  
Maja Przybyłowska ◽  
Krystyna Dzierzbicka ◽  
Szymon Kowalski ◽  
Klaudia Chmielewska ◽  
Iwona Inkielewicz-Stepniak
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Amyloid Plaque ◽  
Β Amyloid ◽  
Derivatives Of ◽  
And Oxidative Stress ◽  
Pro Inflammatory Cytokines

: The aim of this work is review of tacrine analogues from the last three years, which were not included in the latest review work, donepezil and galantamine hybrids from 2015 and rivastigmine derivatives from 2014. In this account we summarize the efforts toward the development and characterization of non-toxic inhibitors of cholinesterases based on mentioned drugs with various interesting additional properties such as antioxidant, decreasing β-amyloid plaque aggregation, nitric oxide production, pro-inflammatory cytokines release, monoamine oxidase-B activity, cytotoxicity and oxidative stress in vitro and in animal model that classify these hybrids as potential multifunctional therapeutic agents for Alzheimer’s disease. Moreover, herein, we have described the cholinergic hypothesis, mechanisms of neurodegeneration and current pharmacotherapy of Alzheimer’s disease which is based on the restoration of cholinergic function through blocking enzymes that break down acetylcholine.

scholarly journals Synergistic Interferon-Alpha-Based Combinations for Treatment of SARS-CoV-2 and Other Viral Infections

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2489
Author(s):  
Aleksandr Ianevski ◽  
Rouan Yao ◽  
Eva Zusinaite ◽  
Laura Sandra Lello ◽  
Sainan Wang ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Side Effects ◽  
Severe Acute Respiratory Syndrome ◽  
Viral Infections ◽  
Therapeutic Potential ◽  
Clinical Development ◽  
Rna Transcription ◽  
Synthesis And Processing ◽  
Synergistic Combinations

Background: There is an urgent need for new antivirals with powerful therapeutic potential and tolerable side effects. Methods: Here, we tested the antiviral properties of interferons (IFNs), alone and with other drugs in vitro. Results: While IFNs alone were insufficient to completely abolish replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), IFNα, in combination with remdesivir, EIDD-2801, camostat, cycloheximide, or convalescent serum, proved to be more effective. Transcriptome and metabolomic analyses revealed that the IFNα–remdesivir combination suppressed SARS-CoV-2-mediated changes in Calu-3 cells and lung organoids, although it altered the homeostasis of uninfected cells and organoids. We also demonstrated that IFNα combinations with sofosbuvir, telaprevir, NITD008, ribavirin, pimodivir, or lamivudine were effective against HCV, HEV, FLuAV, or HIV at lower concentrations, compared to monotherapies. Conclusions: Altogether, our results indicated that IFNα can be combined with drugs that affect viral RNA transcription, protein synthesis, and processing to make synergistic combinations that can be attractive targets for further pre-clinical and clinical development against emerging and re-emerging viral infections.

Chyavanprash: Choice of Drug for immunity boosting and health supplements during COVID -19 pandemic

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 1346-1350
Author(s):  
Bharat Rathi ◽  
Renu Rathi ◽  
Vinod Ade ◽  
Akshay Pargaonkar
Keyword(s):  
Therapeutic Potential ◽  
Age Groups ◽  
Pharmacological Activities ◽  
Common People ◽  
The World ◽  
The Common ◽  
Made In ◽  
Health Supplements

Chyavanprash a known Ayurvedic formulation formulated by sage Chyavan to impart youth, charm, strength & prolonged life. It is very much valued for possessing numerous health benefits with respect to the preventive, curative and promotive aspects of health. Chyavanprash can be consumed throughout the year. Several scientific evidences support its wholesome and safe healthy tonic status that is favorable for all age groups and genders alike. In modern days, it has gained mammoth popularity throughout the world. CP is prepared with Amalaki (Emblica officinalis) as a prime drug with other nutrient rich herbs help to preserve stamina, strength and vitality. Various pre clinical (in vivo & in vitro), Experimental, Analytical and clinical studies conducted on CP and its individual components revealed its various pharmacological activities most of which are suggestive of immunity enhancer and health supplements. Hence an attempt is made in the present paper to find out and explore the scientific evidences based on therapeutic potential of CP with respect to immunity and health supplements and make evidences available to the common people to combat the COVID-19 menace effectively.

Perspectives for the use of N-acetylcysteine as a candidate drug to treat COVID-19

2020 ◽  
Vol 20 ◽  
Author(s):  
Pan Luo ◽  
Yi Liu ◽  
Dong Liu ◽  
Juan Li
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Clinical Efficacy ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Antiviral Drugs ◽  
Potential Functions ◽  
Remedial Measure ◽  
Pharmacological Activities ◽  
Candidate Drug ◽  
Promising Therapeutic Agent

: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has become an ongoing pandemic worldwide. However, there are no vaccines or antiviral drugs with proven clinical efficacy. Therefore, a remedial measure is urgently needed to combat with the devastating COVID-19. The pharmacological activities of N-acetylcysteine (NAC) and its potential functions in inhibiting the progression of COVID19 make it a promising therapeutic agent in COVID-19. In this mini-review, we discussed the therapeutic potential of NAC in COVID-19 from the perspective of its multisite pharmacological actions.

A Review of Saurauia roxburghii Wall. (Actinidiacaea) as a Traditional Medicinal Plant, Its Phytochemical Study and Therapeutic Potential

2020 ◽  
Vol 20 (19) ◽  
pp. 2036-2051
Author(s):  
Afsana Nahrin ◽  
Md. Junaid ◽  
Syeda Samira Afrose ◽  
Muhammad Shaiful Alam ◽  
S.M. Zahid Hosen ◽  
...  
Keyword(s):  
Ursolic Acid ◽  
Therapeutic Potential ◽  
Wide Spectrum ◽  
Relevant Information ◽  
In Vitro Tests ◽  
Pharmacological Activities ◽  
Phytochemical Study ◽  
Corosolic Acid

Saurauia roxburghii Wall. is an interesting plant, found growing chiefly along the eastern and south-eastern countries of Asia. The various ethnic groups of these regions use the plant as a medication for relieving a wide spectrum of diseases and conditions, including indigestion, boils, fever, gout, piles, eczema, asthma, ulcers, bronchitis, epilepsy, and hepatitis B. This review aims to appraise the vernacular information, botanical characterization, geographical distribution, traditional uses, phytochemistry, and pharmacological activities of S. roxburghii as well as to conduct a critical analysis on the findings. To understand the therapeutic potential and provide an overall idea about the ethnomedicinal practices, phytochemistry, and pharmacological activities of S. roxburghii, relevant information was collected via a library and electronic search of online journals, books, and reputed databases. Phytochemical examination revealed the presence of alkaloids, glycosides, O-glycosides, flavonoids, carbohydrates, saponins, steroids, reducing sugars, tannins, phlobatannins, and triterpenoids. The sterols were identified as Stigmasterol and beta-Sitosterol. The triterpenes were found to be Ursolic acid, Corosolic acid, Maslinic acid, 24-Hydroxy corosolic acid, 3b,7b,24-trihydroxy-urs-12-en-28-oic acid, Oleanolic acid, beta-Amyrin, cis-3-O-p-Hydroxycinnamoyl ursolic acid, trans-3-O-p- Hydroxycinnamoyl ursolic acid, and 7,24-dihydroxyursolic acid. Several in-vivo and in-vitro tests revealed anti-bacterial, anti-cancer, anti-diabetic, anti-oxidant, and anti-viral activities of the plant leaves. Detailed analysis of the information collected on S. roxburghii suggested some promising leads for future drug development. However, many scientific gaps were found in the study of this and further extensive investigation is needed to fully understand the mechanism of action of the active constituents and exploit its therapeutic promises.

scholarly journals Synthesis of a Novel α-Glucosyl Ginsenoside F1 by Cyclodextrin Glucanotransferase and Its In Vitro Cosmetic Applications

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 142 ◽  
Author(s):  
Seong Moon ◽  
Hye Lee ◽  
Ramya Mathiyalagan ◽  
Yu Kim ◽  
Dong Yang ◽  
...  
Keyword(s):  
Quantum Coherence ◽  
Dermal Fibroblast ◽  
Multiple Bond ◽  
Proton Nuclear Magnetic Resonance ◽  
Cyclodextrin Glucanotransferase ◽  
The Novel ◽  
Pharmacological Activities ◽  
Matrix Metalloproteinase 1 ◽  
Derivatives Of

Ginsenosides from Panax ginseng (Korean ginseng) are unique triterpenoidal saponins that are considered to be responsible for most of the pharmacological activities of P. ginseng. However, the various linkage positions cause different pharmacological activities. In this context, we aimed to synthesize new derivatives of ginsenosides with unusual linkages that show enhanced pharmacological activities. Novel α-glycosylated derivatives of ginsenoside F1 were synthesized from transglycosylation reactions of dextrin (sugar donor) and ginsenoside F1 (acceptor) by the successive actions of Toruzyme®3.0L, a cyclodextrin glucanotransferase. One of the resultant products was isolated and identified as (20S)-3β,6α,12β-trihydroxydammar-24ene-(20-O-β-D-glucopyranosyl-(1→2)-α-D-glucopyranoside) by various spectroscopic characterization techniques of fast atom bombardment-mass spectrometry (FAB-MS), infrared spectroscopy (IR), proton-nuclear magnetic resonance (1H-NMR), 13C-NMR, gradient heteronuclear single quantum coherence (gHSQC), and gradient heteronuclear multiple bond coherence (gHMBC). As expected, the novel α-glycosylated ginsenoside F1 (G1-F1) exhibited increased solubility, lower cytotoxicity toward human dermal fibroblast cells (HDF), and higher tyrosinase activity and ultraviolet A (UVA)-induced inhibitory activity against matrix metalloproteinase-1 (MMP-1) than ginsenoside F1. Since F1 has been reported as an antiaging and antioxidant agent, the enhanced efficacies of the novel α-glycosylated ginsenoside F1 suggest that it might be useful in cosmetic applications after screening.

scholarly journals Imperata cylindrica: A Review of Phytochemistry, Pharmacology, and Industrial Applications

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1454
Author(s):  
Young-Kyung Jung ◽  
Dongyun Shin
Keyword(s):  
Medicinal Plant ◽  
Therapeutic Potential ◽  
Chemical Constituents ◽  
Industrial Applications ◽  
Imperata Cylindrica ◽  
Pharmacological Activities ◽  
Wide Range ◽  
Pharmacological Studies

Imperata cylindrica is a medicinal plant native to southwestern Asia and the tropical and subtropical zones. To date, 72 chemical constituents have been isolated and identified from I. cylindrica Among these compounds, saponins, flavonoids, phenols, and glycosides are the major constituents. Investigations of pharmacological activities of I. cylindrica revealed that this edible medicinal herb exhibits a wide range of therapeutic potential including immunomodulatory, antibacterial, antitumor, anti-inflammatory, and liver protection activities both in vivo and in vitro. The purpose of this review is to provide an overview of I. cylindrica studies until 2019. This article also intends to review advances in the botanical, phytochemical, and pharmacological studies and industrial applications of I. cylindrica, which will provide a useful bibliography for further investigations and applications of I. cylindrica in medicines and foods.

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