Target-Centered Drug Repurposing Predictions of Human Angiotensin-Converting Enzyme 2 (ACE2) and Transmembrane Protease Serine Subtype 2 (TMPRSS2) Interacting Approved Drugs for Coronavirus Disease 2019 (COVID-19) Treatment through a Drug-Target Interaction Deep Learning Model

Yoonjung Choi, Bonggun Shin, Keunsoo Kang, Sungsoo Park, Bo Ram Beck

10.3390/v12111325

Research curated

Abstract

Previously, our group predicted commercially available Food and Drug Administration (FDA) approved drugs that can inhibit each step of the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using a deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI). Unfortunately, additional clinically significant treatment options since the approval of remdesivir are scarce. To overcome the current coronavirus disease 2019 (COVID-19) more efficiently, a treatment strategy that controls not only SARS-CoV-2 replication but also the host entry step should be considered. In this study, we used MT-DTI to predict FDA approved drugs that may have strong affinities for the angiotensin-converting enzyme 2 (ACE2) receptor and the transmembrane protease serine 2 (TMPRSS2) which are essential for viral entry to the host cell. Of the 460 drugs with Kd of less than 100 nM for the ACE2 receptor, 17 drugs overlapped with drugs that inhibit the interaction of ACE2 and SARS-CoV-2 spike reported in the NCATS OpenData portal. Among them, enalaprilat, an ACE inhibitor, showed a Kd value of 1.5 nM against the ACE2. Furthermore, three of the top 30 drugs with strong affinity prediction for the TMPRSS2 are anti-hepatitis C virus (HCV) drugs, including ombitasvir, daclatasvir, and paritaprevir. Notably, of the top 30 drugs, AT1R blocker eprosartan and neuropsychiatric drug lisuride showed similar gene expression profiles to potential TMPRSS2 inhibitors. Collectively, we suggest that drugs predicted to have strong inhibitory potencies to ACE2 and TMPRSS2 through the DTI model should be considered as potential drug repurposing candidates for COVID-19.

Source: PubMed

Related molecules

Name	Synonyms	Genes
Angiotensin-converting enzyme 2	ACE-related carboxypeptidase, ACE2	ACE2
Bremelanotide
Transmembrane serine 2	TMPRSS2, Serine protease 10	TMPRSS2, PRSS10
Talazoparib
Tacrolimus	FK506
Eprosartan
Lisuride
Panobinostat
Bosutinib
Dasatinib	Sprycel, Dasanix
Aprepitant	Emend

Related interactions

Target	Drug	Type	Result
Angiotensin-converting enzyme 2	Bremelanotide	Computational	positive
Transmembrane serine 2	Bremelanotide	Computational	positive
Angiotensin-converting enzyme 2	Talazoparib	Computational	positive
Transmembrane serine 2	Talazoparib	Computational	positive
Angiotensin-converting enzyme 2	Dasatinib	Computational	positive
Transmembrane serine 2	Tacrolimus	Computational	positive
Transmembrane serine 2	Eprosartan	Computational	positive
Transmembrane serine 2	Lisuride	Computational	positive
Transmembrane serine 2	Aprepitant	Computational	positive
Transmembrane serine 2	Panobinostat	Computational	positive
Transmembrane serine 2	Bosutinib	Computational	positive