MCCS: a novel recognition pattern-based method for fast track discovery of anti-SARS-CoV-2 drugs.
Abstract
Given the scale and rapid spread of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, or 2019-nCoV), there is an urgent need to identify therapeutics that are effective against COVID-19 before vaccines are available. Since the current rate of SARS-CoV-2 knowledge acquisition via traditional research methods is not sufficient to match the rapid spread of the virus, novel strategies of drug discovery for SARS-CoV-2 infection are required. Structure-based virtual screening for example relies primarily on docking scores and does not take the...
Source: Briefings in Bioinformatics - October 20, 2020 Category: Bioinformatics Authors: Feng Z, Chen M, Xue Y, Liang T, Chen H, Zhou Y, Nolin TD, Smith RB, Xie XQ Tags: Brief Bioinform Source Type: research
Intravenous Zanamivir: A Viable Option for Critically Ill Patients With Influenza.
CONCLUSIONS: The available information suggests that the intravenous formulation of zanamivir offers a viable alternative treatment for critically ill patients with influenza, especially when resistance to other agents is present.
PMID: 33016090 [PubMed - as supplied by publisher] (Source: The Annals of Pharmacotherapy)
Source: The Annals of Pharmacotherapy - October 4, 2020 Category: Drugs & Pharmacology Authors: Slain D Tags: Ann Pharmacother Source Type: research
Novel insights into the treatment of SARS-CoV-2 infection: An overview of current clinical trials.
Abstract
The emergence of the global pandemic caused by the novel SARS-CoV-2 virus has motivated scientists to find a definitive treatment or a vaccine against it in the shortest possible time. Current efforts towards this goal remain fruitless without a full understanding of the behavior of the virus and its adaptor proteins. This review provides an overview of the biological properties, functional mechanisms, and molecular components of SARS-CoV-2, along with investigational therapeutic and preventive approaches for this virus. Since the proteolytic cleavage of the S protein is critical for virus penetra...
Source: International Journal of Biological Macromolecules - September 25, 2020 Category: Biochemistry Authors: Oroojalian F, Haghbin A, Baradaran B, Hemat N, Shahbazi MA, Baghi HB, Mokhtarzadeh A, Hamblin MR Tags: Int J Biol Macromol Source Type: research
Molecules, Vol. 25, Pages 4248: Five Novel Non-Sialic Acid-Like Scaffolds Inhibit In Vitro H1N1 and H5N2 Neuraminidase Activity of Influenza a Virus
s Scior
Neuraminidase (NA) of influenza viruses enables the virus to access the cell membrane. It degrades the sialic acid contained in extracellular mucin. Later, it is responsible for releasing newly formed virions from the membrane of infected cells. Both processes become key functions within the viral cycle. Therefore, it is a therapeutic target for research of the new antiviral agents. Structure–activity relationships studies have revealed which are the important functional groups for the receptor–ligand interaction. Influenza virus type A NA activity was inhibited by five scaffolds wit...
Source: Molecules - September 15, 2020 Category: Chemistry Authors: Luis M árquez-Domínguez Julio Reyes-Leyva Irma Herrera-Camacho Gerardo Santos-L ópez Thomas Scior Tags: Article Source Type: research
Evaluation of Cell-Penetrating Peptides as Versatile, Effective Absorption Enhancers: Relation to Molecular Weight and Inherent Epithelial Drug Permeability
ConclusionsCPPs are useful as oral absorption enhancers for low-permeable drugs. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - September 3, 2020 Category: Drugs & Pharmacology Source Type: research
Substitutions at H134 and in the 430-loop region in influenza B neuraminidases can confer reduced susceptibility to multiple neuraminidase inhibitors.
Abstract
With the introduction of the influenza specific neuraminidase inhibitors (NAIs) in 1999, there were concerns about the emergence and spread of resistant viruses in the community setting. Surveillance and testing of community isolates for their susceptibility to the NAIs was initially carried out by the Neuraminidase Inhibitor Susceptibility Network (NISN).and has subsequently been taken on by the global WHO influenza network laboratories. During the NISN surveillance, we identified two Yamagata lineage influenza B viruses with amino acid substitutions of H134Y (B/Auckland/2/2001) or W438R (B/Yokoh...
Source: Antiviral Research - July 31, 2020 Category: Virology Authors: Mohr PG, Williams J, Tashiro M, Streltsov VA, McKimm-Breschkin JL Tags: Antiviral Res Source Type: research
Functional neuraminidase inhibitor resistance motifs in avian influenza A(H5Nx) viruses.
In this study we introduced four NAI resistance-associated mutations (N2 numbering) previously found in human infections into the NA of three current AIV subtypes of the H5Nx genotype that threaten the poultry industry and human health: highly pathogenic H5N8, H5N6 and H5N2. Using the established MUNANA assay we showed that a R292K substitution in H5N6 and H5N2 viruses significantly reduced susceptibility to three licenced NAIs: oseltamivir, zanamivir and peramivir. In contrast the mutations E119V, H274Y and N294S had more variable effects with NAI susceptibility being drug- and strain-specific. We measured the replicative...
Source: Antiviral Research - July 31, 2020 Category: Virology Authors: Bialy D, Shelton H Tags: Antiviral Res Source Type: research
Probing antiviral drugs against SARS-CoV-2 through virus-drug association prediction based on the KATZ method.
In this study, 96 virus-drug associations (VDAs) from 12 viruses including SARS-CoV-2 and similar viruses and 78 small molecules are selected. Complete genomic sequence similarity of viruses and chemical structure similarity of drugs are then computed. A KATZ-based VDA prediction method (VDA-KATZ) is developed to infer possible drugs associated with SARS-CoV-2. VDA-KATZ obtained the best AUCs of 0.8803 when the walking length is 2. The predicted top 3 antiviral drugs against SARS-CoV-2 are remdesivir, oseltamivir, and zanamivir. Molecular docking is conducted between the predicted top 10 drugs and the virus spike protein/h...
Source: Genomics - July 30, 2020 Category: Genetics & Stem Cells Authors: Zhou L, Wang J, Liu G, Lu Q, Dong R, Tian G, Yang J, Peng L Tags: Genomics Source Type: research
Laninamivir-Interferon- λ1 Combination Treatment Promotes Resistance by Influenza A Virus More Rapidly Than Laninamivir Alone.
We examined the effectiveness of co-treatment with two distinct classes of anti-influenza drugs, i.e., neuraminidase (NA) inhibitor, laninamivir, and interferon (IFN)-λ1, against the emergence of drug-resistant virus variants in vitro We serially passaged pandemic A/California/04/09 (A(H1N1)pdm09) influenza virus in a human lung epithelial cell line (Calu-3) in the presence or absence of increasing concentrations of laninamivir or laninamivir plus IFN-λ1. Surprisingly, laninamivir used in combination with IFN-λ1 promoted the emergence of the E119G NA mutation five passages earlier than laninamivir alone (passage 2 vs pa...
Source: Antimicrobial Agents and Chemotherapy - May 10, 2020 Category: Microbiology Authors: Adams SE, Lugovtsev VY, Kan A, Bovin NV, Donnelly RP, Ilyushina NA Tags: Antimicrob Agents Chemother Source Type: research
Drugs Past Their Expiration Date
Date: July 27, 2020
Issue #:
1603Summary:
Healthcare providers are often asked if drugs can
be used past their expiration date. Because of legal
restrictions and liability concerns, manufacturers do
not sanction such use and usually do not comment
on the safety or effectiveness of their products beyond
the date on the label. Since our last article on this
subject, more data have become available. (Source: The Medical Letter)
Source: The Medical Letter - April 29, 2020 Category: Drugs & Pharmacology Authors: admin Tags: Adrenaclick Amphetamine Antiviral drugs Aspirin Atropine Auvi-Q Drug Safety Epinephrine Epipen Naloxone Oseltamivir Relenza Tamiflu Tetracyclines Zanamivir Source Type: research
Alternative Regimens of Neuraminidase Inhibitors for Therapy of Hospitalized Adults with Influenza: A Systematic Review of Randomized Controlled Trials
ConclusionHigher compared to standard doses of NAIs or systemic peramivir therapy compared to oral oseltamivir therapy did not demonstrate benefit. (Source: Advances in Therapy)
Source: Advances in Therapy - April 27, 2020 Category: Drugs & Pharmacology Source Type: research
Development of Novel Anti-influenza Thiazolides with Relatively Broad-spectrum Antiviral Potentials.
In this study, we report a series of novel thiazolides derived from an FDA-approved drug nitazoxanide with antiviral activity against influenza and a broad range of viruses. The preferred candidates 4a and 4d showed significantly enhanced anti-influenza potentials with 10-fold improvement, compared with nitazoxanide, and were effective against a variety of influenza subtypes including oseltamivir-resistant strains. Notably, the combination using of compounds 4a/4d and oseltamivir carboxylate or zanamivir displayed synergistic antiviral effect against oseltamivir-resistant strain. Mode of action analysis demonstrated that c...
Source: Antimicrobial Agents and Chemotherapy - April 19, 2020 Category: Microbiology Authors: Zhao L, Yan Y, Dai Q, Li X, Xu K, Zou G, Yang K, Li W, Guo X, Yang J, Li Y, Xia Q, Cao R, Zhong W Tags: Antimicrob Agents Chemother Source Type: research
Identification of entry inhibitors with 4-aminopiperidine scaffold targeting group 1 influenza A virus.
In this study, we report the identification of compound CBS1116 with a 4-aminopiperidine scaffold from a chemical library screen as an entry inhibitor specifically targeting two group 1 influenza A viruses, A/Puerto Rico/8/34 (H1N1) and recombinant low pathogenic avian H5N1 virus (A/Vietnam/1203/04, VN04Low). Mechanism of action study shows that CBS1116 interferes with the HA-mediated fusion process. Further structure activity relationship study generated a more potent compound CBS1117 which has a 50% inhibitory concentration of 70 nM and a selectivity index of ∼4000 against A/Puerto Rico/8/34 (H1N1) infection in human...
Source: Antiviral Research - March 24, 2020 Category: Virology Authors: Hussein AFA, Cheng H, Tundup S, Antanasijevic A, Varhegyi E, Perez J, AbdulRahman EM, Elenany MG, Helal S, Caffrey M, Peet N, Manicassamy B, Rong L Tags: Antiviral Res Source Type: research
Association of moderately abnormal behavior and administered neuraminidase inhibitors.
Authors: Sugawara T, Ohkusa Y, Taniguchi K, Miyazaki C, Momoi MY, Okabe N
Abstract
Our earlier study investigated the incidence of severe abnormal behavior associated with neuraminidase inhibitors (NIs), but some studies have specifically examined the association of oseltamivir use and moderately abnormal behavior. Therefore, this study was undertaken to assess associations between moderately abnormal behavior and administered drugs. All cases of patients with influenza who exhibited moderately abnormal behavior were reported to us by physicians of all sentinel clinics and hospitals for influenza throughou...
Source: Drug Discoveries and Therapeutics - February 28, 2020 Category: Drugs & Pharmacology Tags: Drug Discov Ther Source Type: research
Global update on the susceptibilities of human influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2017–2018
Publication date: Available online 28 January 2020Source: Antiviral ResearchAuthor(s): Emi Takashita, Rod S. Daniels, Seiichiro Fujisaki, Vicki Gregory, Larisa V. Gubareva, Weiijuan Huang, Aeron C. Hurt, Angie Lackenby, Ha T. Nguyen, Dmitriy Pereyaslov, Merryn Roe, Magdi Samaan, Kanta Subbarao, Herman Tse, Dayan Wang, Hui-Ling Yen, Wenqing Zhang, Adam MeijerAbstractThe global analysis of neuraminidase inhibitor (NAI) susceptibility of influenza viruses has been conducted since the 2012–13 period. In 2018 a novel cap-dependent endonuclease inhibitor, baloxavir, that targets polymerase acidic subunit (PA) was approved for ...
Source: Antiviral Therapy - January 30, 2020 Category: Virology Source Type: research
