tetano
Editor, Senior Moderator
Antiviral Res
. 2020 Dec 9;185:104996.
doi: 10.1016/j.antiviral.2020.104996. Online ahead of print.
Antiviral activity against Middle East Respiratory Syndrome Coronavirus by Montelukast, an anti-asthma drug
Hanjie Jonathan Gan[SUP] 1 [/SUP], Amaravadhi Harikishore[SUP] 1 [/SUP], Jihye Lee[SUP] 2 [/SUP], Sangeun Jeon[SUP] 2 [/SUP], Sreekanth Rajan[SUP] 1 [/SUP], Ming Wei Chen[SUP] 1 [/SUP], Jun Long Neo[SUP] 1 [/SUP], Seungtaek Kim[SUP] 3 [/SUP], Ho Sup Yoon[SUP] 4 [/SUP]
Affiliations
Abstract
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.
Keywords: Drug repurposing; MERS-CoV; Montelukast; Receptor-binding domain (RBD).
. 2020 Dec 9;185:104996.
doi: 10.1016/j.antiviral.2020.104996. Online ahead of print.
Antiviral activity against Middle East Respiratory Syndrome Coronavirus by Montelukast, an anti-asthma drug
Hanjie Jonathan Gan[SUP] 1 [/SUP], Amaravadhi Harikishore[SUP] 1 [/SUP], Jihye Lee[SUP] 2 [/SUP], Sangeun Jeon[SUP] 2 [/SUP], Sreekanth Rajan[SUP] 1 [/SUP], Ming Wei Chen[SUP] 1 [/SUP], Jun Long Neo[SUP] 1 [/SUP], Seungtaek Kim[SUP] 3 [/SUP], Ho Sup Yoon[SUP] 4 [/SUP]
Affiliations
- PMID: 33309540
- PMCID: PMC7726485
- DOI: 10.1016/j.antiviral.2020.104996
Abstract
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.
Keywords: Drug repurposing; MERS-CoV; Montelukast; Receptor-binding domain (RBD).