Montelukast and Telmisartan as Inhibitors of SARS-CoV-2 Omicron Variant
Nirmitee Mulgaonkar, Haoqi Wang, Junrui Zhang, Christopher M Roundy, Wendy Tang, Sankar Prasad Chaki, Alex Pauvolid-Corrêa, Gabriel L Hamer, Sandun Fernando
Pharmaceutics, doi:10.3390/pharmaceutics15071891
Earlier studies with montelukast (M) and telmisartan (T) have revealed their potential antiviral properties against SARS-CoV-2 wild-type (WT) but have not assessed their efficacy against emerging Variants of Concern (VOCs) such as Omicron. Our research fills this gap by investigating these drugs' impact on VOCs, a topic that current scientific literature has largely overlooked. We employed computational methodologies, including molecular mechanics and machine learning tools, to identify drugs that could potentially disrupt the SARS-CoV-2 spike RBD-ACE2 protein interaction. This led to the identification of two FDA-approved small molecule drugs, M and T, conventionally used for treating asthma and hypertension, respectively. Our study presents an additional potential use for these drugs as antivirals. Our results show that both M and T can inhibit not only the WT SARS-CoV-2 but also, in the case of M, the Omicron variant, without reaching cytotoxic concentrations. This novel finding fills an existing gap in the literature and introduces the possibility of repurposing these drugs for SARS-CoV-2 VOCs, an essential step in responding to the evolving global pandemic.
Supplementary Materials: The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/pharmaceutics15071891/s1, Figure S1 : Protein information of SARS-CoV-2 RBD-ACE2 complex (PDB: 6VW1) with secondary structure assessment; Table S1 : RMSD and RMSF evaluation for the last 25 ns and entire MD simulation trajectory, respectively; Table S2 : Prime/MM-GBSA binding free energy calculations for MD of screened compounds with SARS-CoV-2 RBD-ACE2 complex from wild type (WT), and omicron variant; Figure S2: (A
Conflicts of Interest: The authors declare no conflict of interest.
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