Antiviral drugs suppress infection of 2019-nCoV spike pseudotyped virus by interacting with ACE2 protein.

Abstract

The outbreak of coronavirus disease 2019 (COVID-19) has induced a large number of deaths worldwide. Angiotensin-converting enzyme 2 (ACE2) is the entry receptor for the 2019 novel coronavirus (2019-nCoV) to infect the host cells. Therefore, ACE2 may be an important target for the prevention and treatment of COVID-19. The aim of this study was to investigate the inhibition effect of valaciclovir hydrochloride (VACV), zidovudine (ZDV), saquinavir (SQV), and efavirenz (EFV) on 2019-nCoV infection. The results of molecule docking and surface plasmon resonance showed that VACV, ZDV, SQV, and EFV could bind to ACE2 protein, with the KD value of (4.33 ± 0.09) e-8 , (6.29 ± 1.12) e-6 , (2.37 ± 0.59) e-5 , and (4.85 ± 1.57) e-5 M, respectively. But only ZDV and EFV prevent the 2019-nCoV spike pseudotyped virus to enter ACE2-HEK293T cells with an EC50 value of 4.30 ± 1.46 and 3.92 ± 1.36 μM, respectively. ZDV and EFV also have a synergistic effect on preventing entry of virus into cells. In conclusion, ZDV and EFV suppress 2019-nCoV infection of ACE2-HEK293T cells by interacting with ACE2.

• Authors: Jue Wang, Yongjing Zhang, Shiling Hu, Haoyun Bai, Zhuoyin Xue, Yanhong Liu, Weina Ma
• Journal: Journal of biochemical and molecular toxicology (J Biochem Mol Toxicol) Vol. 36 Issue 2 Pg. e22948 (Feb 2022) ISSN: 1099-0461 [Electronic] United States
• PMID: 34755435 (Publication Type: Journal Article)
• Copyright: © 2021 Wiley Periodicals LLC.

Chemical References

• Antiviral Agents
• ACE protein, human
• Peptidyl-Dipeptidase A

Topics

• Allosteric Site
• Antiviral Agents (metabolism, pharmacology)
• COVID-19 (prevention & control, virology)
• HEK293 Cells
• Humans
• Molecular Docking Simulation
• Peptidyl-Dipeptidase A (drug effects, metabolism)
• Protein Binding
• SARS-CoV-2 (drug effects)
• Surface Plasmon Resonance
• Viral Pseudotyping
• COVID-19 Drug Treatment