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Inhibition of Chikungunya Virus Infection by 4-Hydroxy-1-Methyl-3-(3-morpholinopropanoyl)quinoline-2(1H)-one (QVIR) Targeting nsP2 and E2 Proteins
[Image: see text] The re-emergence of Chikungunya virus (CHIKV) infection in humans with no approved antiviral therapies or vaccines is one of the major problems with global significance. In the present investigation, we screened 80 in-house quinoline derivatives for their anti-CHIKV activity by com...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047676/ https://www.ncbi.nlm.nih.gov/pubmed/33869959 http://dx.doi.org/10.1021/acsomega.1c00447 |
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author | Islamuddin, Mohammad Afzal, Obaid Khan, Wajihul Hasan Hisamuddin, Malik Altamimi, Abdulmalik Saleh Alfawaz Husain, Ibraheem Kato, Kentaro Alamri, Mubarak A. Parveen, Shama |
author_facet | Islamuddin, Mohammad Afzal, Obaid Khan, Wajihul Hasan Hisamuddin, Malik Altamimi, Abdulmalik Saleh Alfawaz Husain, Ibraheem Kato, Kentaro Alamri, Mubarak A. Parveen, Shama |
author_sort | Islamuddin, Mohammad |
collection | PubMed |
description | [Image: see text] The re-emergence of Chikungunya virus (CHIKV) infection in humans with no approved antiviral therapies or vaccines is one of the major problems with global significance. In the present investigation, we screened 80 in-house quinoline derivatives for their anti-CHIKV activity by computational techniques and found 4-hydroxy-1-methyl-3-(3-morpholinopropanoyl)quinoline-2(1H)-one (QVIR) to have potential binding affinities with CHIKV nsP2 and E2 glycoproteins. QVIR was evaluated in vitro for its anti-CHIKV potential. QVIR showed strong inhibition of CHIKV infection with an EC(50) (50% effective concentration) value of 2.2 ± 0.49 μM without significant cytotoxicity (CC(50) > 200 μM) and was chosen for further elucidation of its antiviral mechanism. The infectious viral particle formation was abolished by approximately 72% at a QVIR concentration of 20 μM during infection in the BHK-21 cell line, and the CHIKV RNA synthesis was diminished by 84% for nsP2 as well as 74% for E2, whereas the levels of viral proteins were decreased by 69.9% for nsP2 and 53.9% for E2. Flow cytometry analysis confirmed a huge decline in the expression of viral nsP2 and E2 proteins by 71.84 and 67.7%, respectively. Time of addition experiments indicated that QVIR inhibited viral infection at early and late stages of viral replication cycle, and the optimal inhibition was observed at 16 h post infection. The present study advocates for the first time that QVIR acts as a substantial and potent inhibitor against CHIKV and might be as an auspicious novel drug candidate for the development of therapeutic agents against CHIKV infections. |
format | Online Article Text |
id | pubmed-8047676 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-80476762021-04-16 Inhibition of Chikungunya Virus Infection by 4-Hydroxy-1-Methyl-3-(3-morpholinopropanoyl)quinoline-2(1H)-one (QVIR) Targeting nsP2 and E2 Proteins Islamuddin, Mohammad Afzal, Obaid Khan, Wajihul Hasan Hisamuddin, Malik Altamimi, Abdulmalik Saleh Alfawaz Husain, Ibraheem Kato, Kentaro Alamri, Mubarak A. Parveen, Shama ACS Omega [Image: see text] The re-emergence of Chikungunya virus (CHIKV) infection in humans with no approved antiviral therapies or vaccines is one of the major problems with global significance. In the present investigation, we screened 80 in-house quinoline derivatives for their anti-CHIKV activity by computational techniques and found 4-hydroxy-1-methyl-3-(3-morpholinopropanoyl)quinoline-2(1H)-one (QVIR) to have potential binding affinities with CHIKV nsP2 and E2 glycoproteins. QVIR was evaluated in vitro for its anti-CHIKV potential. QVIR showed strong inhibition of CHIKV infection with an EC(50) (50% effective concentration) value of 2.2 ± 0.49 μM without significant cytotoxicity (CC(50) > 200 μM) and was chosen for further elucidation of its antiviral mechanism. The infectious viral particle formation was abolished by approximately 72% at a QVIR concentration of 20 μM during infection in the BHK-21 cell line, and the CHIKV RNA synthesis was diminished by 84% for nsP2 as well as 74% for E2, whereas the levels of viral proteins were decreased by 69.9% for nsP2 and 53.9% for E2. Flow cytometry analysis confirmed a huge decline in the expression of viral nsP2 and E2 proteins by 71.84 and 67.7%, respectively. Time of addition experiments indicated that QVIR inhibited viral infection at early and late stages of viral replication cycle, and the optimal inhibition was observed at 16 h post infection. The present study advocates for the first time that QVIR acts as a substantial and potent inhibitor against CHIKV and might be as an auspicious novel drug candidate for the development of therapeutic agents against CHIKV infections. American Chemical Society 2021-03-31 /pmc/articles/PMC8047676/ /pubmed/33869959 http://dx.doi.org/10.1021/acsomega.1c00447 Text en © 2021 The Authors. Published by American Chemical Society Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Islamuddin, Mohammad Afzal, Obaid Khan, Wajihul Hasan Hisamuddin, Malik Altamimi, Abdulmalik Saleh Alfawaz Husain, Ibraheem Kato, Kentaro Alamri, Mubarak A. Parveen, Shama Inhibition of Chikungunya Virus Infection by 4-Hydroxy-1-Methyl-3-(3-morpholinopropanoyl)quinoline-2(1H)-one (QVIR) Targeting nsP2 and E2 Proteins |
title | Inhibition of Chikungunya Virus
Infection by 4-Hydroxy-1-Methyl-3-(3-morpholinopropanoyl)quinoline-2(1H)-one (QVIR) Targeting nsP2 and E2 Proteins |
title_full | Inhibition of Chikungunya Virus
Infection by 4-Hydroxy-1-Methyl-3-(3-morpholinopropanoyl)quinoline-2(1H)-one (QVIR) Targeting nsP2 and E2 Proteins |
title_fullStr | Inhibition of Chikungunya Virus
Infection by 4-Hydroxy-1-Methyl-3-(3-morpholinopropanoyl)quinoline-2(1H)-one (QVIR) Targeting nsP2 and E2 Proteins |
title_full_unstemmed | Inhibition of Chikungunya Virus
Infection by 4-Hydroxy-1-Methyl-3-(3-morpholinopropanoyl)quinoline-2(1H)-one (QVIR) Targeting nsP2 and E2 Proteins |
title_short | Inhibition of Chikungunya Virus
Infection by 4-Hydroxy-1-Methyl-3-(3-morpholinopropanoyl)quinoline-2(1H)-one (QVIR) Targeting nsP2 and E2 Proteins |
title_sort | inhibition of chikungunya virus
infection by 4-hydroxy-1-methyl-3-(3-morpholinopropanoyl)quinoline-2(1h)-one (qvir) targeting nsp2 and e2 proteins |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047676/ https://www.ncbi.nlm.nih.gov/pubmed/33869959 http://dx.doi.org/10.1021/acsomega.1c00447 |
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