IN SILICO EVALUATION OF POTASSIUM USNATE

A new coronavirus appears in China in December 2019, subsequently threatening the world, it was identified as Covid-19. Its main symptomatic characteristic is directly linked to acute respiratory failure, however there are asymptomatic cases of the disease, mainly in the group not considered at risk. For the treatment of the disease a variety ofantiviral drugs have been tested, with conflicting results. The use of computer-assisted drugs is essential for the development of new therapeutic alternatives for various diseases, once they reduce the time consumed in the initial screening tests, in addition to determining the possible mechanisms of action and reducing toxicity. In our study, we evaluated the interaction of viral components of the coronavirus with potassium usnate, salt derived from lichenic origin and with proven antimicrobial and antitumor activities. Derived from ussic acid, potassium usnate showed low energy for complex formation, this interaction occurs between the usnate salt and the structures of proteinase 3CLpro and enzyme Mpro, all key parts of Covid-19. In addition, in order to prove in silico the use of potassium usnate, they were tested and compared with other approved drugs and candidates for clinical trials to combat the new coronavirus.

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A narrative review of newly approved drugs for COVID-19

10.31219/osf.io/7f3qs ◽

2020 ◽

Author(s):

Rajmohan Seetharaman ◽

Jaisen Lokhande

Keyword(s):

Technical Assistance ◽

Scientific Information ◽

Mechanisms Of Action ◽

New Drugs ◽

Efficacy And Safety ◽

Regulatory Authorities ◽

Viral Structure ◽

The World ◽

Approved Drugs ◽

Regulatory Flexibility

COVID-19 disease is swiftly spreading over the globe. There were no specific approved drugs or therapies at the start of the pandemic. Hence, the management of these patients involves optimized supportive care. Researchers worldwide are analyzing the viral structure viruses pathophysiology to develop new drugs and repurpose the currently approved drugs. Regulatory authorities worldwide, such as the USFDA, EMA, CDSCO, etc. are working closely with these scientists. They are expediting their efforts by providing advice, technical assistance, regulatory flexibility, and leveraging on scientific information from the trials conducted across various parts of the globe. These efforts have led to emergency use authorizations and restricted emergency use approvals of a few drugs, namely remdesivir, favipiravir, and 2% propofol emulsion for use in COVID-19 patients. The USFDA has revoked the approval of chloroquine and hydroxychloroquine. Many more new drugs are in the pipeline for their antiviral or immunomodulatory or other supportive mechanisms of action. These drugs are under the radar of regulatory authorities who are monitoring their efficacy and safety firmly as the world hopes to find a solution to combat this pandemic.

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Apitherapy for Osteoarthritis: Perspectives from Basic Research

Complementary Medicine Research ◽

10.1159/000505015 ◽

2020 ◽

Vol 27 (3) ◽

pp. 184-192 ◽

Cited By ~ 1

Author(s):

Andrés Jagua-Gualdrón ◽

José Adolfo Peña-Latorre ◽

Roger Edwin Fernadez-Bernal

Keyword(s):

Rheumatic Disease ◽

Royal Jelly ◽

Basic Research ◽

The Elderly ◽

Mechanisms Of Action ◽

Therapeutic Tool ◽

Current State ◽

The World ◽

Ancient Times ◽

Therapeutic Alternatives

Osteoarthritis is one of the most common rheumatic disease in the world and one of the leading causes of disability in the elderly. There is still no curative management for the disease, so the search for new therapeutic alternatives continues. Apitherapy is a therapeutic tool based on the use of beehive products used since ancient times and, at present, their mechanism of action begins to be known. Many of the mechanisms of action of the beehive products are useful for chronic articular pathophysiological processes such as those described in osteoarthritis. This article presents a review of the current state of understanding of the mechanisms through which bee venom, propolis, honey, pollen, and royal jelly may act on osteoarthritis.

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In silico and In vitro Investigations of Antihelmintic Activities of some Selected Approved Drugs

10.1101/837427 ◽

2019 ◽

Author(s):

Christopher Arinze Agube ◽

Daniel Lotanna Ajaghaku ◽

Ikemefuna Chijioke Uzochukwu

Keyword(s):

Drug Discovery ◽

In Silico ◽

Public Health Problem ◽

Alternative Methods ◽

Computational Techniques ◽

Major Public Health Problem ◽

Life Years ◽

The World ◽

Approved Drugs

AbstractThe search for alternative methods to mitigate the drawbacks associated with wet laboratory drug discovery has been a major challenge in drug design and has limited the options available in the fight against most Neglected Tropical Diseases (NTDs) such as helminthiasis. We investigated the binding affinities of some approved drugs to Ascaris suum mitochondrial rhodoquinol fumarate reductase enzyme (MRFR),an essential enzyme for ascaris survival, and the possibility of repurposing these drugs as antihelmintic agents using in silico molecular docking and in vitro paralysis and mortality times of fifteen selected front runners.Two hundred approved drugs were selected from ZINC® database based on bioactivity scores while MRFR(PDB code, 3vra) was obtained from the Protein Data Bank (PDB). Both were prepared using AutoDock tools v.1.5.6 and Chimerav.1.9.The docking protocol was validated by computationally reproducing the binding of atpenin to MRFR. The selected approved drugs and the receptor were docked using AutoDockVina v. 4.0. The docking results were analyzed using PyMoL v. 1.4.1.The paralysis and mortality times of the identified frontrunners against Pheretima posthuma were determined in vitro and synergistic testings were done by the checkerboard method. Fifteen drugs had binding free energies between −7.825 to 11.025 kcal/mol while four of these drugs (mefloquine, doxycycline, mepacrine and proguanil) emerged as major frontrunners by both in silico and in vitro assessments. The paralysis and mortality times of the four drugs were between 0.33-0.50 hr as against 1.80-2.36 hr for albendazole. They were therefore predicted to have ability to affect MRFR in the same manner as atpenin hence, suggestive of potential antihelmintic activity. In vivo investigation of these frontrunner drugs is strongly recommended.Author SummaryFor decades, intestinal worm infections have been a major public health problem particularly in the tropical regions of the world with infection figures put at 5.3b [16].This disease is often associated with poor hygiene and sanitation hence is predominant in the resource-poor nations with physical infrastructural deficit [8].Children between the ages of 2-10 years are the most vulnerable by reason of their hand habits with morbidity leading to compromise of physical and cognitive development while several sufferers have had to live disability-adjusted life years as a consequence [12].Efforts at implementing improved hygiene and mass deworming campaigns have not delivered the intended outcomes with many reports coming from clinicians regarding gradual development of resistance to the standard treatments [9].Given the huge cost and time invested in traditional drug discovery and the rarity of this disease in regions of the world with the resources for research, no new drugs have been developed in the past two decades [18].The advent of computational techniques in drug discovery has come to mitigate these drawbacks. This study exploited this technique to full effect and through laboratory assays and clinical investigation of selected approved drugs, mepacrine and doxycycline were identified as potential antihelmintic agents fit for combination therapy.

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Mechanisms of action of antihyperglycemic mexicanolides isolated from Swietenia humillis: in vivo and in silico approaches

Planta Medica ◽

10.1055/s-0036-1596301 ◽

2016 ◽

Vol 81 (S 01) ◽

pp. S1-S381 ◽

Cited By ~ 1

Author(s):

B Ovalle-Magallanes ◽

A Madariaga-Mazón ◽

A Navarrete ◽

R Mata

Keyword(s):

In Silico ◽

Mechanisms Of Action

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One-Shot Fabrication of Polymeric Hollow Microneedles by Standard Photolithography

Polymers ◽

10.3390/polym13040520 ◽

2021 ◽

Vol 13 (4) ◽

pp. 520 ◽

Cited By ~ 2

Author(s):

Principia Dardano ◽

Selene De Martino ◽

Mario Battisti ◽

Bruno Miranda ◽

Ilaria Rea ◽

...

Keyword(s):

Light Propagation ◽

World Market ◽

Emerging Technology ◽

Standard Formulation ◽

Proof Of Concept ◽

Fabrication Technique ◽

The World ◽

Small Doses ◽

Approved Drugs ◽

Hollow Microneedles

Microneedles (MNs) are an emerging technology in pharmaceutics and biomedicine, and are ready to be commercialized in the world market. However, solid microneedles only allow small doses and time-limited administration rates. Moreover, some well-known and already approved drugs need to be re-formulated when supplied by MNs. Instead, hollow microneedles (HMNs) allow for rapid, painless self-administrable microinjection of drugs in their standard formulation. Furthermore, body fluids can be easily extracted for analysis by a reverse use of HMNs, thus making them perfect for sensing issues and theranostics applications. The fabrication of HMNs usually requires several many-step processes, increasing the costs and consequently decreasing the commercial interest. Photolithography is a well-known fabrication technique in microelectronics and microfluidics that fabricates MNs. In this paper, authors show a proof of concept of a patented, easy and one-shot fabrication of two kinds of HMNs: (1) Symmetric HMNs with a “volcano” shape, made by using a photolithographic mask with an array of transparent symmetric rings; and (2) asymmetric HMNs with an oblique aperture, like standard hypodermic steel needles, made by using an array of transparent asymmetric rings, defined by two circles, which centers are slightly mismatched. Simulation of light propagation, fabrication process, and preliminary results on ink microinjection are presented.

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Deepening of In Silico Evaluation of SARS-CoV-2 Detection RT-qPCR Assays in the Context of New Variants

Genes ◽

10.3390/genes12040565 ◽

2021 ◽

Vol 12 (4) ◽

pp. 565

Author(s):

Mathieu Gand ◽

Kevin Vanneste ◽

Isabelle Thomas ◽

Steven Van Gucht ◽

Arnaud Capron ◽

...

Keyword(s):

Performance Evaluation ◽

Severe Acute Respiratory Syndrome ◽

In Silico ◽

The Other ◽

Viral Rna ◽

Potential Threat ◽

The World

For 1 year now, the world is undergoing a coronavirus disease-2019 (COVID-19) pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The most widely used method for COVID-19 diagnosis is the detection of viral RNA by RT-qPCR with a specific set of primers and probe. It is important to frequently evaluate the performance of these tests and this can be done first by an in silico approach. Previously, we reported some mismatches between the oligonucleotides of publicly available RT-qPCR assays and SARS-CoV-2 genomes collected from GISAID and NCBI, potentially impacting proper detection of the virus. In the present study, 11 primers and probe sets investigated during the first study were evaluated again with 84,305 new SARS-CoV-2 unique genomes collected between June 2020 and January 2021. The lower inclusivity of the China CDC assay targeting the gene N has continued to decrease with new mismatches detected, whereas the other evaluated assays kept their inclusivity above 99%. Additionally, some mutations specific to new SARS-CoV-2 variants of concern were found to be located in oligonucleotide annealing sites. This might impact the strategy to be considered for future SARS-CoV-2 testing. Given the potential threat of the new variants, it is crucial to assess if they can still be correctly targeted by the primers and probes of the RT-qPCR assays. Our study highlights that considering the evolution of the virus and the emergence of new variants, an in silico (re-)evaluation should be performed on a regular basis. Ideally, this should be done for all the RT-qPCR assays employed for SARS-CoV-2 detection, including also commercial tests, although the primer and probe sequences used in these kits are rarely disclosed, which impedes independent performance evaluation.

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Protein nutritional quality, amino acid profile, anti-amylase and anti-glucosidase properties of microalgae: Inhibition and mechanisms of action through in vitro and in silico studies

LWT ◽

10.1016/j.lwt.2021.112023 ◽

2021 ◽

pp. 112023

Author(s):

Roghayeh Siahbalaei ◽

Gholamreza Kavoosi ◽

Mostafa Noroozi

Keyword(s):

Amino Acid ◽

In Silico ◽

Nutritional Quality ◽

Amino Acid Profile ◽

Mechanisms Of Action ◽

In Silico Studies

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Mining of high throughput screening database reveals AP-1 and autophagy pathways as potential targets for COVID-19 therapeutics

Scientific Reports ◽

10.1038/s41598-021-86110-8 ◽

2021 ◽

Vol 11 (1) ◽

Cited By ~ 2

Author(s):

Hu Zhu ◽

Catherine Z. Chen ◽

Srilatha Sakamuru ◽

Jinghua Zhao ◽

Deborah K. Ngan ◽

...

Keyword(s):

Clinical Trials ◽

High Throughput Screening ◽

Animal Studies ◽

Cytopathic Effect ◽

Mechanisms Of Action ◽

Activity Profile ◽

Pathway Activity ◽

Global Pandemic ◽

Approved Drugs

AbstractThe recent global pandemic of the Coronavirus disease 2019 (COVID-19) caused by the new coronavirus SARS-CoV-2 presents an urgent need for the development of new therapeutic candidates. Many efforts have been devoted to screening existing drug libraries with the hope to repurpose approved drugs as potential treatments for COVID-19. However, the antiviral mechanisms of action of the drugs found active in these phenotypic screens remain largely unknown. In an effort to deconvolute the viral targets in pursuit of more effective anti-COVID-19 drug development, we mined our in-house database of approved drug screens against 994 assays and compared their activity profiles with the drug activity profile in a cytopathic effect (CPE) assay of SARS-CoV-2. We found that the autophagy and AP-1 signaling pathway activity profiles are significantly correlated with the anti-SARS-CoV-2 activity profile. In addition, a class of neurology/psychiatry drugs was found to be significantly enriched with anti-SARS-CoV-2 activity. Taken together, these results provide new insights into SARS-CoV-2 infection and potential targets for COVID-19 therapeutics, which can be further validated by in vivo animal studies and human clinical trials.

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