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

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.

Montelukast and Coronavirus Disease 2019: A Scoping Review

“…9,10 Moreover, the beneficial anti-viral activity of MK against middle-east respiratory syndrome coronavirus (MERS-CoV) has been recently reported. 11 So, considering the common ancestral origin of SARS-CoV-2 and MERS-CoV, 12 the same effect of MK can be expected in SARS-CoV-2. Additionally, Barré J, et al, summarized a list of potential properties of MK reported in previous studies including improving fiber re-organization and long-term functional recovery after brain ischemia, alleviating the ischemia/reperfusion, anti-atheromatous, antioxidant, and anti-fibrosis ones.…”

Montelukast Inhibits HCoV-OC43 Infection as a Viral Inactivator

“…The homology of Mpro between HCoV-OC43 and SARS-CoV-2 is about 48% and the IC50 (~28 µM) of montelukast against SARS-CoV-2′s Mpro reported by them is much higher than the concentration we used, which may explain why only entry of HCoV-OC43 was affected in this study. It was also found that montelukast sodium hydrate (MSH) significantly inhibited the entry of MERS-spike pseudovirion at 20 µM, indicated by an enhanced reduction in luciferase activity, and IC50 values of MSH with authentic MERS-CoV in both pre-treatment and co-treatment experiments being both approximately 3 µM [ 17 ].Due to the shortage of biosafety level three containment facilities to us, the inhibitory effect of the montelukast on authentic SARS-CoV-2 virus entry could not be tested at present. However, considering the similarity between SARS-CoV-2 and HCoV-OC43, it is likely that montelukast might block SARS-CoV-2 entry in the same way as montelukast blocks HCoV-OC43.…”

“…Montelukast, a leukotriene receptor antagonist safely used in asthma patients for many years, has the potential to inhibit SARS-CoV-2 and MERS-CoV infection [ 17 , 18 , 19 ] and has the ability to inhibit Zika virus infection by disrupting its integrity [ 20 ]. In this study, we found that montelukast could also effectively inhibit the infection of HCoV-OC43 by screening FDA-approved drugs.…”

Main Chemotypes of SARS-CoV-2 Reproduction Inhibitors

“…Quinoline derivatives 81-91 [57,[86][87][88][89][90][91][92][93][94][95] are often mentioned among heterocyclic compounds active against coronaviruses. This group of compounds includes well-known antimalarial agents, specifi cally hydroxychlorolroquine 82 [87][88][89], which has been used in clinical practice for some time to treat patients with COVID-19 (Fig.…”