Antiviral activity against Middle East Respiratory Syndrome coronavirus by Montelukast, an anti-asthma drug

Middle East Respiratory Syndrome (MERS) is a respiratory disease caused by a coronavirus (MERS-CoV). Since its emergence in 2012, nosocomial amplifications have led to its high epidemic potential and mortality rate of 34.5%. To date, there is an unmet need for vaccines and specific therapeutics for...

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Main Authors: Gan, Hanjie Jonathan, Harikishore, Amaravadhi, Lee, Jihye, Jeon, Sangeun, Rajan, Sreekanth, Chen, Ming Wei, Neo, Jun Long, Kim, Seungtaek, Yoon, Ho Sup
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2022
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Online Access:https://hdl.handle.net/10356/159916
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1599162022-07-05T08:44:33Z Antiviral activity against Middle East Respiratory Syndrome coronavirus by Montelukast, an anti-asthma drug Gan, Hanjie Jonathan Harikishore, Amaravadhi Lee, Jihye Jeon, Sangeun Rajan, Sreekanth Chen, Ming Wei Neo, Jun Long Kim, Seungtaek Yoon, Ho Sup School of Biological Sciences Science::Biological sciences MERS-CoV Receptor-Binding Domain Middle East Respiratory Syndrome (MERS) is a respiratory disease caused by a coronavirus (MERS-CoV). Since its emergence in 2012, nosocomial amplifications have led to its high epidemic potential and mortality rate of 34.5%. To date, there is an unmet need for vaccines and specific therapeutics for this disease. Available treatments are either supportive medications in use for other diseases or those lacking specificity requiring higher doses. The viral infection mode is initiated by the attachment of the viral spike glycoprotein to the human Dipeptidyl Peptidase IV (DPP4). Our attempts to screen antivirals against MERS led us to identify montelukast sodium hydrate (MSH), an FDA-approved anti-asthma drug, as an agent attenuating MERS-CoV infection. We showed that MSH directly binds to MERS-CoV-Receptor-Binding Domain (RBD) and inhibits its molecular interaction with DPP4 in a dose-dependent manner. Our cell-based inhibition assays using MERS pseudovirions demonstrated that viral infection was significantly inhibited by MSH and was further validated using infectious MERS-CoV culture. Thus, we propose MSH as a potential candidate for therapeutic developments against MERS-CoV infections. Nanyang Technological University National Research Foundation (NRF) This study was supported by Research Student Scholarship from Nanyang Technological University Singapore (given to H.J. Gan), NRF2017M3A9G6068245, and CRC-16-01-KRICT. 2022-07-05T08:44:33Z 2022-07-05T08:44:33Z 2021 Journal Article Gan, H. J., Harikishore, A., Lee, J., Jeon, S., Rajan, S., Chen, M. W., Neo, J. L., Kim, S. & Yoon, H. S. (2021). Antiviral activity against Middle East Respiratory Syndrome coronavirus by Montelukast, an anti-asthma drug. Antiviral Research, 185, 104996-. https://dx.doi.org/10.1016/j.antiviral.2020.104996 0166-3542 https://hdl.handle.net/10356/159916 10.1016/j.antiviral.2020.104996 33309540 2-s2.0-85097801797 185 104996 en NRF2017M3A9G6068245 Antiviral Research © 2020 Elsevier B.V. All rights reserved.
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences
MERS-CoV
Receptor-Binding Domain
spellingShingle Science::Biological sciences
MERS-CoV
Receptor-Binding Domain
Gan, Hanjie Jonathan
Harikishore, Amaravadhi
Lee, Jihye
Jeon, Sangeun
Rajan, Sreekanth
Chen, Ming Wei
Neo, Jun Long
Kim, Seungtaek
Yoon, Ho Sup
Antiviral activity against Middle East Respiratory Syndrome coronavirus by Montelukast, an anti-asthma drug
description Middle East Respiratory Syndrome (MERS) is a respiratory disease caused by a coronavirus (MERS-CoV). Since its emergence in 2012, nosocomial amplifications have led to its high epidemic potential and mortality rate of 34.5%. To date, there is an unmet need for vaccines and specific therapeutics for this disease. Available treatments are either supportive medications in use for other diseases or those lacking specificity requiring higher doses. The viral infection mode is initiated by the attachment of the viral spike glycoprotein to the human Dipeptidyl Peptidase IV (DPP4). Our attempts to screen antivirals against MERS led us to identify montelukast sodium hydrate (MSH), an FDA-approved anti-asthma drug, as an agent attenuating MERS-CoV infection. We showed that MSH directly binds to MERS-CoV-Receptor-Binding Domain (RBD) and inhibits its molecular interaction with DPP4 in a dose-dependent manner. Our cell-based inhibition assays using MERS pseudovirions demonstrated that viral infection was significantly inhibited by MSH and was further validated using infectious MERS-CoV culture. Thus, we propose MSH as a potential candidate for therapeutic developments against MERS-CoV infections.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Gan, Hanjie Jonathan
Harikishore, Amaravadhi
Lee, Jihye
Jeon, Sangeun
Rajan, Sreekanth
Chen, Ming Wei
Neo, Jun Long
Kim, Seungtaek
Yoon, Ho Sup
format Article
author Gan, Hanjie Jonathan
Harikishore, Amaravadhi
Lee, Jihye
Jeon, Sangeun
Rajan, Sreekanth
Chen, Ming Wei
Neo, Jun Long
Kim, Seungtaek
Yoon, Ho Sup
author_sort Gan, Hanjie Jonathan
title Antiviral activity against Middle East Respiratory Syndrome coronavirus by Montelukast, an anti-asthma drug
title_short Antiviral activity against Middle East Respiratory Syndrome coronavirus by Montelukast, an anti-asthma drug
title_full Antiviral activity against Middle East Respiratory Syndrome coronavirus by Montelukast, an anti-asthma drug
title_fullStr Antiviral activity against Middle East Respiratory Syndrome coronavirus by Montelukast, an anti-asthma drug
title_full_unstemmed Antiviral activity against Middle East Respiratory Syndrome coronavirus by Montelukast, an anti-asthma drug
title_sort antiviral activity against middle east respiratory syndrome coronavirus by montelukast, an anti-asthma drug
publishDate 2022
url https://hdl.handle.net/10356/159916
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