Berbamine hydrochloride potently inhibits SARS-CoV-2 infection by blocking S protein-mediated membrane fusion

Abstract

COVID-19 caused by SARS-CoV-2 has posed a significant threat to global public health since its outbreak in late 2019. Although there are a few drugs approved for clinical treatment to combat SARS-CoV-2 infection currently, the severity of the ongoing global pandemic still urges the efforts to discover new antiviral compounds. As the viral spike (S) protein plays a key role in mediating virus entry, it becomes a potential target for the design of antiviral drugs against COVID-19. Here, we tested the antiviral activity of berbamine hydrochloride, a bis-benzylisoquinoline alkaloid, against SARS-CoV-2 infection. We found that berbamine hydrochloride could efficiently inhibit SARS-CoV-2 infection in different cell lines. Further experiments showed berbamine hydrochloride inhibits SARS-CoV-2 infection by targeting the viral entry into host cells. Moreover, berbamine hydrochloride and other bis-benzylisoquinoline alkaloids could potently inhibit S-mediated cell-cell fusion. Furthermore, molecular docking results implied that the berbamine hydrochloride could bind to the post fusion core of SARS-CoV-2 S2 subunit. Therefore, berbamine hydrochloride may represent a potential efficient antiviral agent against SARS-CoV-2 infection.

Neuromasts and Olfactory Organs of Zebrafish Larvae Represent Possible Sites of SARS-CoV-2 Pseudovirus Host Cell Entry

“…S1Bb). We also showed that treatment of 293T-ACE2 cells with naringenin, tetrandrine, bafilomycin A1, fangchinoline, or cepharanthine (i.e., previously reported in vitro inhibitors of SARS-CoV-2 infection [ 2 , 19 , 77 , 78 ]) led to a significant inhibition of pseudoviral entry compared with the dimethyl sulfoxide (DMSO) control (Fig. S1C).…”

Identification of potential COVID-19 treatment compounds which inhibit SARS Cov2 prototypic, Delta and Omicron variant infection

“…An earlier report has shown that berbamine inhibits SARS-CoV-2 entry into the target cells by impairing Transient Receptor Potential cation channel, MucoLipin subfamily (TRPMLs)-mediated endolysosomal trafficking of ACE2 ( Huang et al, 2021 ) and could inhibit S-mediated cell-cell fusion. ( Zhang et al, 2022 ). Cepharanthine, a naturally occurring alkaloid extracted from the plant Stephania cepharantha Hayata, has been previously reported to inhibit SARS-CoV-2 binding to target cells and thereby prevent virus entry ( Ohashi et al, 2021 ).…”

Berbamine Hydrochloride Inhibits African Swine Fever Virus Infection In Vitro

“…berbamine hydrochloride is a bis-benzylisoquinoline alkaloid isolated from the traditional Chinese herb Berberis amurensis. Berbaminebe was demonstrated to have antiviral activity against different types of viruses, such as bovine viral diarrhea virus (BVDV), Japanese encephalitis virus (JEV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [22][23][24][25]. Moreover, berbamine regulates multiple cellular biological processes.…”