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

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY(2022)

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摘要
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 K-D 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 mu M, 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.
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关键词
2019-nCoV, ACE2, efavirenz, zidovudine
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