Venetoclax Decreases the Expression of the Spike Protein through Amino Acids Q493 and S494 in SARS-CoV-2

Chih-Chieh Chen; Zhi-Jie Zhuang; Chia-Wei Wu; Yi-Ling Tan; Chen-Hsiu Huang; Chia-Yi Hsu; Eing-Mei Tsai; Tsung-Hua Hsieh

doi:10.3390/cells11121924

Venetoclax Decreases the Expression of the Spike Protein through Amino Acids Q493 and S494 in SARS-CoV-2

Cells. 2022 Jun 14;11(12):1924. doi: 10.3390/cells11121924.

Authors

Chih-Chieh Chen^{1

2}, Zhi-Jie Zhuang¹, Chia-Wei Wu³, Yi-Ling Tan¹, Chen-Hsiu Huang³, Chia-Yi Hsu⁴, Eing-Mei Tsai^{4

5}, Tsung-Hua Hsieh³

Affiliations

¹ Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 804201, Taiwan.
² Rapid Screening Research Center for Toxicology and Biomedicine, National Sun Yat-sen University, Kaohsiung 804201, Taiwan.
³ Department of Medical Research, E-Da Hospital/E-Da Cancer Hospital, I-Shou University, Kaohsiung 82445, Taiwan.
⁴ Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.
⁵ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.

Abstract

The new coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been reported and spread globally. There is an urgent need to take urgent measures to treat and prevent further infection of this virus. Here, we use virtual drug screening to establish pharmacophore groups and analyze the ACE2 binding site of the spike protein with the ZINC drug database and DrugBank database by molecular docking and molecular dynamics simulations. Screening results showed that Venetoclax, a treatment drug for chronic lymphocytic leukemia, has a potential ability to bind to the spike protein of SARS-CoV-2. In addition, our in vitro study found that Venetoclax degraded the expression of the spike protein of SARS-CoV-2 through amino acids Q493 and S494 and blocked the interaction with the ACE2 receptor. Our results suggest that Venetoclax is a candidate for clinical prevention and treatment and deserves further research.

Keywords: COVID-19; SARS-CoV-2; molecular docking; molecular dynamics simulations; spike protein; virtual screening.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acids / metabolism
Angiotensin-Converting Enzyme 2
Bridged Bicyclo Compounds, Heterocyclic
COVID-19 Drug Treatment*
Humans
Molecular Docking Simulation
Peptidyl-Dipeptidase A / metabolism
Protein Binding
SARS-CoV-2*
Spike Glycoprotein, Coronavirus / chemistry
Sulfonamides

Substances

Amino Acids
Bridged Bicyclo Compounds, Heterocyclic
Spike Glycoprotein, Coronavirus
Sulfonamides
spike protein, SARS-CoV-2
Peptidyl-Dipeptidase A
Angiotensin-Converting Enzyme 2
venetoclax

Grants and funding

This work was supported by the Ministry of Science and Technology of Taiwan (grant numbers MOST 110-2314-B-650-004, 110-2314-B-037-041-MY3 and 110-2221-E-110-032-MY3) and by the E-Da Hospital/E-Da Cancer Hospital (ECPJ108008, EDCHT109013 and ECPJ110010).