Clomipramine inhibits dynamin GTPase activity by L-α-phosphatidyl-L-serine stimulation

Author:

Miyoshi Hiroshi1,Otomo Masahiro2,Takahashi Kiyofumi2

Affiliation:

1. St. Marianna University School of Medicine Department of Microbiology, , 2-16-1 Sugao, Miyamae, Kawasaki 216-8511, Japan

2. St. Marianna University School of Medicine Department of Neuropsychiatry, , 2-16-1 Sugao, Miyamae, Kawasaki 216-8511, Japan

Abstract

Abstract Three dynamin isoforms play critical roles in clathrin-dependent endocytosis. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells via clathrin-dependent endocytosis. We previously reported that 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine (clomipramine) inhibits the GTPase activity of dynamin 1, which is in mainly neuron. Therefore, we investigated whether clomipramine inhibits the activity of other dynamin isoforms in this study. We found that, similar to its inhibitory effect on dynamin 1, clomipramine inhibited the l-α-phosphatidyl-l-serine-stimulated GTPase activity of dynamin 2, which is expressed ubiquitously, and dynamin 3, which is expressed in the lung. Inhibition of GTPase activity raises the possibility that clomipramine can suppress SARS-CoV-2 entry into host cells.

Funder

Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan

Publisher

Oxford University Press (OUP)

Subject

Molecular Biology,Biochemistry,General Medicine

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