Tackling Influenza A virus by M2 ion channel blockers: Latest progress and limitations
Eur J Med Chem. 2024 Feb 3;267:116172. doi: 10.1016/j.ejmech.2024.116172. Online ahead of print.ABSTRACTInfluenza outbreaks cause pandemics in millions of people. The treatment of influenza remains a challenge due to significant genetic polymorphism in the influenza virus. Also, developing vaccines to protect against seasonal and pandemic influenza infections is constantly impeded. Thus, antibiotics are the only first line of defense against antigenically distinct strains or new subtypes of influenza viruses. Among several anti-influenza targets, the M2 protein of the influenza virus performs several activities. M2 protein...
Source: European Journal of Medicinal Chemistry - February 8, 2024 Category: Chemistry Authors: Gautam Kumar Kakade Aditi Sakharam Source Type: research
In Situ Spectroscopic Detection of Large-Scale Reorientations of Transmembrane Helices During Influenza A M2 Channel Opening
Angew Chem Int Ed Engl. 2023 Sep 21:e202309069. doi: 10.1002/anie.202309069. Online ahead of print.ABSTRACTViroporins are small ion channels in membranes of enveloped viruses that play key roles during viral life cycles. To use viroporins as drug targets against viral infection requires in-depth mechanistic understanding and, with that, methods that enable investigations under in situ conditions. Here, we apply surface-enhanced infrared absorption (SEIRA) spectroscopy to Influenza A M2 reconstituted within a solid-supported membrane, to shed light on the mechanics of its viroporin function. M2 is a paradigm of pH-activated...
Source: Angewandte Chemie - September 21, 2023 Category: Chemistry Authors: Ronja Rabea Paschke Swantje Mohr Sascha Lange Adam Lange Jacek Kozuch Source Type: research
Antiviral Compounds to Address Influenza Pandemics: An Update from 2016-2022
Curr Med Chem. 2023 Sep 7. doi: 10.2174/0929867331666230907093501. Online ahead of print.ABSTRACTIn recent decades, the world has gained experience of the dangerous effects of pandemic events caused by emerging respiratory viruses. In particular, annual epidemics of influenza are responsible for severe illness and deaths. Even if conventional influenza vaccines represent the most effective tool for preventing virus infections, they are not completely effective in patients with severe chronic disease and immunocompromised and new small molecules have emerged to prevent and control the influenza viruses. Thus, the attention ...
Source: Current Medicinal Chemistry - September 11, 2023 Category: Chemistry Authors: Roberto Romeo Laura Legnani Maria Assunta Chiacchio Salvatore V Giofr è Daniela Iannazzo Source Type: research
Antiviral Compounds to Address Influenza Pandemics: An Update from 2016-2022
Curr Med Chem. 2023 Sep 7. doi: 10.2174/0929867331666230907093501. Online ahead of print.ABSTRACTIn recent decades, the world has gained experience of the dangerous effects of pandemic events caused by emerging respiratory viruses. In particular, annual epidemics of influenza are responsible for severe illness and deaths. Even if conventional influenza vaccines represent the most effective tool for preventing virus infections, they are not completely effective in patients with severe chronic disease and immunocompromised and new small molecules have emerged to prevent and control the influenza viruses. Thus, the attention ...
Source: Current Medicinal Chemistry - September 11, 2023 Category: Chemistry Authors: Roberto Romeo Laura Legnani Maria Assunta Chiacchio Salvatore V Giofr è Daniela Iannazzo Source Type: research
Viruses, Vol. 15, Pages 1684: Elimination of Solanum nigrum ilarvirus 1 and Apple Hammerhead Viroid from Apple Cultivars Using Antivirals Ribavirin, Rimantadine, and Zidovudine
merák
Apple hammerhead viroid (AHVd) was detected in the apple cultivar ‘Šampion’ and in mixed infection with Solanum nigrum ilarvirus 1 (SnIV-1) in the cultivars ‘Selena’ and ‘Jonagored Supra’, using a high-throughput sequencing method. Experiments were conducted to eliminate both pathogens in apples using meristem tip cultures in combination with the antivirotics ribavirin, rimantadine, and zidovudine. Elimination of both pathogens was verified by repeated RT-PCR and qRT-PCR assays after 7–11 months. Elim...
Source: Viruses - August 2, 2023 Category: Virology Authors: Ji ří Sedlák Jaroslava P řibylová Igor Kolo ňuk Josef Špak Ond řej Lenz Mat ěj Semerák Tags: Article Source Type: research
Adamantyl Amines Activity Study Against Mutant Influenza A M2 Channels Identified a Polycyclic Cage Amine Triple blocker Explored with MD simulations and Solid state NMR
ChemMedChem. 2023 Jun 28:e202300182. doi: 10.1002/cmdc.202300182. Online ahead of print.ABSTRACTWe compared the anti-influenza potencies of 57 adamantyl amines and analogs against influenza A virus with serine-31 M2 proton channel, usually termed as WT M2 channel, which is amantadine sensitive. We also tested a sub-set of these compounds against viruses with the amantadine resistant L26F, V27A, A30T, G34E M2 mutant channels. (a) Four compounds inhibited WT M2 virus in vitro with mid-nanomolar and 27 compounds with sub-micromolar to low micromolar potency. (b) Several compounds inhibited L26F M2 virus in vitro with sub-micr...
Source: ChemMedChem - June 28, 2023 Category: Chemistry Authors: Anja Hoffman Marianna Stampolaki Christina Tzitzoglaki Patrick Schmerer Chunlong Ma Kristin D öring Andreea Turcu Jun Wang Santiago Vazquez Michaela Schmidtke Antonios Kolokouris Ioannis Stylianakis Kumar Tekwani Movellan Loren Andreas Stefan Becker Source Type: research
Adamantyl Amines Activity Study Against Mutant Influenza A M2 Channels Identified a Polycyclic Cage Amine Triple blocker Explored with MD simulations and Solid state NMR
ChemMedChem. 2023 Jun 28:e202300182. doi: 10.1002/cmdc.202300182. Online ahead of print.ABSTRACTWe compared the anti-influenza potencies of 57 adamantyl amines and analogs against influenza A virus with serine-31 M2 proton channel, usually termed as WT M2 channel, which is amantadine sensitive. We also tested a sub-set of these compounds against viruses with the amantadine resistant L26F, V27A, A30T, G34E M2 mutant channels. (a) Four compounds inhibited WT M2 virus in vitro with mid-nanomolar and 27 compounds with sub-micromolar to low micromolar potency. (b) Several compounds inhibited L26F M2 virus in vitro with sub-micr...
Source: ChemMedChem - June 28, 2023 Category: Chemistry Authors: Anja Hoffman Marianna Stampolaki Christina Tzitzoglaki Patrick Schmerer Chunlong Ma Kristin D öring Andreea Turcu Jun Wang Santiago Vazquez Michaela Schmidtke Antonios Kolokouris Ioannis Stylianakis Kumar Tekwani Movellan Loren Andreas Stefan Becker Source Type: research
Adamantyl Amines Activity Study Against Mutant Influenza A M2 Channels Identified a Polycyclic Cage Amine Triple blocker Explored with MD simulations and Solid state NMR
ChemMedChem. 2023 Jun 28:e202300182. doi: 10.1002/cmdc.202300182. Online ahead of print.ABSTRACTWe compared the anti-influenza potencies of 57 adamantyl amines and analogs against influenza A virus with serine-31 M2 proton channel, usually termed as WT M2 channel, which is amantadine sensitive. We also tested a sub-set of these compounds against viruses with the amantadine resistant L26F, V27A, A30T, G34E M2 mutant channels. (a) Four compounds inhibited WT M2 virus in vitro with mid-nanomolar and 27 compounds with sub-micromolar to low micromolar potency. (b) Several compounds inhibited L26F M2 virus in vitro with sub-micr...
Source: ChemMedChem - June 28, 2023 Category: Chemistry Authors: Anja Hoffman Marianna Stampolaki Christina Tzitzoglaki Patrick Schmerer Chunlong Ma Kristin D öring Andreea Turcu Jun Wang Santiago Vazquez Michaela Schmidtke Antonios Kolokouris Ioannis Stylianakis Kumar Tekwani Movellan Loren Andreas Stefan Becker Source Type: research
Synthesis and antiviral activity of 1,2,3-triazolyl nucleoside analogues with < em > N < /em > -acetyl-d-glucosamine residue
Nucleosides Nucleotides Nucleic Acids. 2023 Mar 24:1-23. doi: 10.1080/15257770.2023.2189914. Online ahead of print.ABSTRACTA series of 1,2,3-triazolyl nucleoside analogues bearing N-acetyl-D-glucosamine residue was synthesized by the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction of N1-ω-alkynyl derivatives of uracil, 6-methyluracil, thymine and 3,4,6-tri-O-acetyl-2-deoxy-2-acetamido-β-D-glucopyranosyl azide. Antiviral assays revealed the lead compound 3f which showed both the same activity against the influenza virus A H1N1 (IC50=70.7 µM) as the antiviral drug Rimantadine in control (IC50=77 µM) and good...
Source: Nucleosides, Nucleotides and Nucleic Acids - March 24, 2023 Category: Biochemistry Authors: Bulat F Garifullin Leysan R Khabibulina Maya G Belenok Liliya F Saifina Vladimir V Zarubaev Alexander V Slita Alexandrina S Volobueva Vyacheslav E Semenov Vladimir E Kataev Source Type: research
Molecules, Vol. 27, Pages 7797: Essential Oils and Their Compounds as Potential Anti-Influenza Agents
eji
Essential oils (EOs) are chemical substances, mostly produced by aromatic plants in response to stress, that have a history of medicinal use for many diseases. In the last few decades, EOs have continued to gain more attention because of their proven therapeutic applications against the flu and other infectious diseases. Influenza (flu) is an infectious zoonotic disease that affects the lungs and their associated organs. It is a public health problem with a huge health burden, causing a seasonal outbreak every year. Occasionally, it comes as a disease pandemic with unprecedentedly high hospitalization and mortality...
Source: Molecules - November 12, 2022 Category: Chemistry Authors: Ayodeji Oluwabunmi Oriola Adebola Omowunmi Oyedeji Tags: Review Source Type: research
Insights into binding molecular mechanism of hemagglutinin H3N2 of influenza virus complexed with arbidol and its derivative: A molecular dynamics simulation perspective
Comput Biol Chem. 2022 Aug 28;101:107764. doi: 10.1016/j.compbiolchem.2022.107764. Online ahead of print.ABSTRACTRecently, the H3N2 influenza outbreak has caused serious global public health concern for future control of the next influenza pandemic. Since using current anti-influenza drugs targeting neuraminidase (oseltamivir and zanamivir) and the proton M2 channel (amantadine and rimantadine) leads to drug resistance, it is essential to seek new anti-viral agents that act on additional viral targets. Hemagglutinin (HA), a glycoprotein embedded in the viral surface and playing a critical role in influenza the viral replic...
Source: Computational Biology and Chemistry - September 1, 2022 Category: Bioinformatics Authors: Thitiya Boonma Nattharuja Soikudrua Bodee Nutho Thanyada Rungrotmongkol Nadtanet Nunthaboot Source Type: research
Insights into binding molecular mechanism of hemagglutinin H3N2 of influenza virus complexed with arbidol and its derivative: A molecular dynamics simulation perspective
Comput Biol Chem. 2022 Aug 28;101:107764. doi: 10.1016/j.compbiolchem.2022.107764. Online ahead of print.ABSTRACTRecently, the H3N2 influenza outbreak has caused serious global public health concern for future control of the next influenza pandemic. Since using current anti-influenza drugs targeting neuraminidase (oseltamivir and zanamivir) and the proton M2 channel (amantadine and rimantadine) leads to drug resistance, it is essential to seek new anti-viral agents that act on additional viral targets. Hemagglutinin (HA), a glycoprotein embedded in the viral surface and playing a critical role in influenza the viral replic...
Source: Computational Biology and Chemistry - September 1, 2022 Category: Bioinformatics Authors: Thitiya Boonma Nattharuja Soikudrua Bodee Nutho Thanyada Rungrotmongkol Nadtanet Nunthaboot Source Type: research
Insights into binding molecular mechanism of hemagglutinin H3N2 of influenza virus complexed with arbidol and its derivative: A molecular dynamics simulation perspective
Comput Biol Chem. 2022 Aug 28;101:107764. doi: 10.1016/j.compbiolchem.2022.107764. Online ahead of print.ABSTRACTRecently, the H3N2 influenza outbreak has caused serious global public health concern for future control of the next influenza pandemic. Since using current anti-influenza drugs targeting neuraminidase (oseltamivir and zanamivir) and the proton M2 channel (amantadine and rimantadine) leads to drug resistance, it is essential to seek new anti-viral agents that act on additional viral targets. Hemagglutinin (HA), a glycoprotein embedded in the viral surface and playing a critical role in influenza the viral replic...
Source: Computational Biology and Chemistry - September 1, 2022 Category: Bioinformatics Authors: Thitiya Boonma Nattharuja Soikudrua Bodee Nutho Thanyada Rungrotmongkol Nadtanet Nunthaboot Source Type: research
