Repurposing of berbamine hydrochloride to inhibit Ebola virus by targeting viral glycoprotein

Yi, Dongrong; Li, Quanjie; Wang, Han; Lv, Kai; Ma, Ling; Wang, Yujia; Wang, Jing; Zhang, Yongxin; Liu, Mingliang; Li, Xiaoyü; Qi, Jianxun; Shi, Yi; Gao, George F.; Cen, Shan

doi:10.1016/j.apsb.2022.05.023

Cited by 13 publications

(9 citation statements)

References 55 publications

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“…Berbamine is a bis-benzylisoquinoline alkaloid isolated from the traditional Chinese herb Berberis amurensis [ 14 ]. Berbamine inhibits various viruses, including SARS-CoV-2, MERS-CoV, JEV, ASFV, and EBOV [ 17 , 18 , 19 , 20 , 21 ]. For human coronaviruses, berbamine prevents SARS-CoV-2 or MERS-CoV from entering host cells by decreasing the viral receptor levels of ACE2 or DPP4 at the plasma membrane [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…These three compounds have various biological activities, including antiviral, anticancer, and anti-inflammatory activities, by modulating different cell-signaling pathways [ 14 , 15 , 16 ]. In a study of antiviral drugs, BBM was reported to inhibit Middle Respiratory Syndrome Coronavirus (MERS-CoV), Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Japanese encephalitis Virus (JEV), Ebola virus (EBOV), and African Swine Fever Virus (ASFV) infections [ 17 , 18 , 19 , 20 , 21 ]. FAN can inhibit MERS-CoV, Human Coronavirus OC43, and human immunodeficiency virus type 1 (HIV-1) [ 18 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

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Bis-Benzylisoquinoline Alkaloids Inhibit Porcine Epidemic Diarrhea Virus by Disrupting Virus Entry

et al. 2023

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The porcine epidemic diarrhea virus (PEDV), belonging to the α-coronavirus, is the causative agent of porcine epidemic diarrhea (PED). Presently, protection from the existing PEDV vaccine is not effective. Therefore, anti-PEDV compounds should be studied. Berbamine (BBM), Fangchinoline (FAN), and (+)-Fangchinoline (+FAN), are types of bis-benzylisoquinoline alkaloids that are extracted from natural medicinal plants. These bis-benzylisoquinoline alkaloids have various biological activities, including antiviral, anticancer, and anti-inflammatory properties. In this study, we found that BBM, FAN, and +FAN suppressed PEDV activity with a 50% inhibitory concentration of 9.00 µM, 3.54 µM, and 4.68 µM, respectively. Furthermore, these alkaloids can decrease the PEDV-N protein levels and virus titers in vitro. The time-of-addition assay results showed that these alkaloids mainly inhibit PEDV entry. We also found that the inhibitory effects of BBM, FAN, and +FAN on PEDV rely on decreasing the activity of Cathepsin L (CTSL) and Cathepsin B (CTSB) by suppressing lysosome acidification. Taken together, these results indicated that BBM, FAN, and +FAN were effective anti-PEDV natural products that prevented PEDV entry and may be considered novel antiviral drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bis-Benzylisoquinoline Alkaloids Inhibit Porcine Epidemic Diarrhea Virus by Disrupting Virus Entry

et al. 2023

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“…According to the findings of Yi and colleagues, the natural compound EEI-10, also known as berbamine, inhibits EBOV replication in vitro and in vivo. This inhibition was attributed to its capacity to bind to GP after being cleaved by host cathepsins, thus preventing GP binding to NPC1 [ 139 ]. Although this research suggests that employing berbamine for EBOV is drug repurposing, berbamine is not yet approved for human use, as no results are returned upon searching for this compound on the FDA or EMA websites and on drug databases [ 140 – 142 ].…”

Section: Ebola Virus: From a Therapeutic Point Of Viewmentioning

confidence: 99%

Navigating the Complex Landscape of Ebola Infection Treatment: A Review of Emerging Pharmacological Approaches

Almeida-Pinto,

Pinto,

Rocha

2024

Infect Dis Ther

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In 1976 Ebola revealed itself to the world, marking the beginning of a series of localized outbreaks. However, it was the Ebola outbreak that began in 2013 that incited fear and anxiety around the globe. Since then, our comprehension of the virus has been steadily expanding. Ebola virus (EBOV), belonging to the Orthoebolavirus genus of the Filoviridae family, possesses a non-segmented, negative single-stranded RNA genome comprising seven genes that encode multiple proteins. These proteins collectively orchestrate the intricate process of infecting host cells. It is not possible to view each protein as monofunctional. Instead, they synergistically contribute to the pathogenicity of the virus. Understanding this multifaceted replication cycle is crucial for the development of effective antiviral strategies. Currently, two antibody-based therapeutics have received approval for treating Ebola virus disease (EVD). In 2022, the first evidence-based clinical practice guideline dedicated to specific therapies for EVD was published. Although notable progress has been made in recent years, deaths still occur. Consequently, there is an urgent need to enhance the therapeutic options available to improve the outcomes of the disease. Emerging therapeutics can target viral proteins as direct-acting antivirals or host factors as host-directed antivirals. They both have advantages and disadvantages. One way to bypass some disadvantages is to repurpose already approved drugs for non-EVD indications to treat EVD. This review offers detailed insight into the role of each viral protein in the replication cycle of the virus, as understanding how the virus interacts with host cells is critical to understanding how emerging therapeutics exert their activity. Using this knowledge, this review delves into the intricate mechanisms of action of current and emerging therapeutics.

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“…Berberine hydrochloride, a Chinese medicinal monomer derived from Sankezhen (Berberidis Radix), binds to the EBOV glycoprotein and disrupts its interaction with the viral receptor, preventing the virus from fusing with the cell membrane and protecting mice from lethal EBOV infection. [90] This discovery provides a possibility for applying berberine hydrochloride in EBOV prevention and control. Lianhua Qingwen capsules () have the effects of clearing pestilence, removing toxins, ventilating lungs, and discharging heat.…”

Section: Clinical Evidence and Mechanisms Of Chinese Medicine For Tre...mentioning

confidence: 99%

Clinical evidence and mechanisms of traditional Chinese medicine in major diseases

Luo,

Li,

Wang

et al. 2023

Sci Tradit Chin Med

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Major diseases cause a double blow to patients' physical and mental health and family life and pose a great challenge to the healthcare system. The high incidence of major diseases compels us to constantly improve the medical prevention and treatment system to reduce disability and death rates as much as possible. Traditional Chinese medicine (TCM) has been widely used in the treatment of malignancies and cardiovascular and cerebrovascular diseases such as myocardial infarction and stroke, in the rehabilitation of patients with these diseases, as well as in the prevention and treatment of new outbreaks of infectious diseases and other major illnesses. After the coronavirus disease 2019 outbreak, the clinical application of “three prescriptions and three drugs” has greatly increased the cure rate, reduced the mortality rate, and provided a “Chinese solution” for global epidemic prevention and control. This article reviewed the clinical evidence and mechanisms of action of TCM in the prevention and treatment of major diseases, summarized the advances, and proposed future research directions to provide scientific evidence to expand the clinical application of TCM and improve its efficacy for the benefit of all humankind.

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Repurposing of berbamine hydrochloride to inhibit Ebola virus by targeting viral glycoprotein

Cited by 13 publications

References 55 publications

Bis-Benzylisoquinoline Alkaloids Inhibit Porcine Epidemic Diarrhea Virus by Disrupting Virus Entry

Bis-Benzylisoquinoline Alkaloids Inhibit Porcine Epidemic Diarrhea Virus by Disrupting Virus Entry

Navigating the Complex Landscape of Ebola Infection Treatment: A Review of Emerging Pharmacological Approaches

Clinical evidence and mechanisms of traditional Chinese medicine in major diseases

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