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Repurposing of Doxycycline to Hinder the Viral Replication of SARS-CoV-2: From in silico to in vitro Validation

Since the rapid spread of coronavirus disease (COVID-19) became a global pandemic, healthcare ministries around the world have recommended specific control methods such as quarantining infected peoples, identifying infections, wearing mask, and practicing hand hygiene. Since no effective treatment f...

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Autores principales: Alexpandi, Rajaiah, Gendrot, Mathieu, Abirami, Gurusamy, Delandre, Océane, Fonta, Isabelle, Mosnier, Joel, Mariadasse, Richard, Jeyakanthan, Jeyaraman, Pandian, Shunmugiah Karutha, Pradines, Bruno, Ravi, Arumugam Veera
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9115549/
https://www.ncbi.nlm.nih.gov/pubmed/35602049
http://dx.doi.org/10.3389/fmicb.2022.757418
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author Alexpandi, Rajaiah
Gendrot, Mathieu
Abirami, Gurusamy
Delandre, Océane
Fonta, Isabelle
Mosnier, Joel
Mariadasse, Richard
Jeyakanthan, Jeyaraman
Pandian, Shunmugiah Karutha
Pradines, Bruno
Ravi, Arumugam Veera
author_facet Alexpandi, Rajaiah
Gendrot, Mathieu
Abirami, Gurusamy
Delandre, Océane
Fonta, Isabelle
Mosnier, Joel
Mariadasse, Richard
Jeyakanthan, Jeyaraman
Pandian, Shunmugiah Karutha
Pradines, Bruno
Ravi, Arumugam Veera
author_sort Alexpandi, Rajaiah
collection PubMed
description Since the rapid spread of coronavirus disease (COVID-19) became a global pandemic, healthcare ministries around the world have recommended specific control methods such as quarantining infected peoples, identifying infections, wearing mask, and practicing hand hygiene. Since no effective treatment for COVID-19 has yet been discovered, a variety of drugs approved by Food and Drug Administration (FDA) have been suggested for repurposing strategy. In the current study, we predicted that doxycycline could interact with the nucleotide triphosphate (NTP) entry channel, and is therefore expected to hinder the viral replication of SARS-CoV-2 RNA-dependent RNA-polymerase (RdRp) through docking analysis. Further, the molecular dynamics results revealed that the RdRp-Doxycycline complex was structurally relatively stable during the dynamic period (100 ns), and its complex maintained close contact with their active catalytic domains of SARS-CoV-2 RdRp. The molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) calculation of binding free energy also showed that the doxycycline has worthy affinities with SARS-CoV-2 RdRp. As expected, doxycycline effectively inhibited the viral replication of IHU strains of SARS-CoV-2 (IHUMI-3 and IHUMI-6), identified from the hospitalized patients in IHU Méditerranée Infection (IHUMI), Marseille, France. Moreover, doxycycline inhibited the viral load in vitro at both on-entry and after viral entry of IHU variants of SARS-CoV-2. The results suggest that doxycycline exhibits strains-dependant antiviral activity against COVID-19. As a result, the current study concludes that doxycycline may be more effective in combination with other drugs for better COVID-19 treatment efficacy.
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spelling pubmed-91155492022-05-19 Repurposing of Doxycycline to Hinder the Viral Replication of SARS-CoV-2: From in silico to in vitro Validation Alexpandi, Rajaiah Gendrot, Mathieu Abirami, Gurusamy Delandre, Océane Fonta, Isabelle Mosnier, Joel Mariadasse, Richard Jeyakanthan, Jeyaraman Pandian, Shunmugiah Karutha Pradines, Bruno Ravi, Arumugam Veera Front Microbiol Microbiology Since the rapid spread of coronavirus disease (COVID-19) became a global pandemic, healthcare ministries around the world have recommended specific control methods such as quarantining infected peoples, identifying infections, wearing mask, and practicing hand hygiene. Since no effective treatment for COVID-19 has yet been discovered, a variety of drugs approved by Food and Drug Administration (FDA) have been suggested for repurposing strategy. In the current study, we predicted that doxycycline could interact with the nucleotide triphosphate (NTP) entry channel, and is therefore expected to hinder the viral replication of SARS-CoV-2 RNA-dependent RNA-polymerase (RdRp) through docking analysis. Further, the molecular dynamics results revealed that the RdRp-Doxycycline complex was structurally relatively stable during the dynamic period (100 ns), and its complex maintained close contact with their active catalytic domains of SARS-CoV-2 RdRp. The molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) calculation of binding free energy also showed that the doxycycline has worthy affinities with SARS-CoV-2 RdRp. As expected, doxycycline effectively inhibited the viral replication of IHU strains of SARS-CoV-2 (IHUMI-3 and IHUMI-6), identified from the hospitalized patients in IHU Méditerranée Infection (IHUMI), Marseille, France. Moreover, doxycycline inhibited the viral load in vitro at both on-entry and after viral entry of IHU variants of SARS-CoV-2. The results suggest that doxycycline exhibits strains-dependant antiviral activity against COVID-19. As a result, the current study concludes that doxycycline may be more effective in combination with other drugs for better COVID-19 treatment efficacy. Frontiers Media S.A. 2022-05-04 /pmc/articles/PMC9115549/ /pubmed/35602049 http://dx.doi.org/10.3389/fmicb.2022.757418 Text en Copyright © 2022 Alexpandi, Gendrot, Abirami, Delandre, Fonta, Mosnier, Mariadasse, Jeyakanthan, Pandian, Pradines and Ravi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Alexpandi, Rajaiah
Gendrot, Mathieu
Abirami, Gurusamy
Delandre, Océane
Fonta, Isabelle
Mosnier, Joel
Mariadasse, Richard
Jeyakanthan, Jeyaraman
Pandian, Shunmugiah Karutha
Pradines, Bruno
Ravi, Arumugam Veera
Repurposing of Doxycycline to Hinder the Viral Replication of SARS-CoV-2: From in silico to in vitro Validation
title Repurposing of Doxycycline to Hinder the Viral Replication of SARS-CoV-2: From in silico to in vitro Validation
title_full Repurposing of Doxycycline to Hinder the Viral Replication of SARS-CoV-2: From in silico to in vitro Validation
title_fullStr Repurposing of Doxycycline to Hinder the Viral Replication of SARS-CoV-2: From in silico to in vitro Validation
title_full_unstemmed Repurposing of Doxycycline to Hinder the Viral Replication of SARS-CoV-2: From in silico to in vitro Validation
title_short Repurposing of Doxycycline to Hinder the Viral Replication of SARS-CoV-2: From in silico to in vitro Validation
title_sort repurposing of doxycycline to hinder the viral replication of sars-cov-2: from in silico to in vitro validation
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9115549/
https://www.ncbi.nlm.nih.gov/pubmed/35602049
http://dx.doi.org/10.3389/fmicb.2022.757418
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