Berbamine prevents SARS-CoV-2 entry and transmission

Srikanth Sadhu; Sandeep Goswami; Ritika Khatri; Bharat Lohiya; Virendra Singh; Rahul Yadav; Vinayaka Das; Manas Ranjan Tripathy; Prabhanjan Dwivedi; Mitul Srivastava; Shailendra Mani; Shailendra Asthana; Sweety Samal; Amit Awasthi

doi:10.1016/j.isci.2024.111347

Berbamine prevents SARS-CoV-2 entry and transmission

iScience. 2024 Nov 8;27(12):111347. doi: 10.1016/j.isci.2024.111347. eCollection 2024 Dec 20.

Authors

Srikanth Sadhu^{1

2}, Sandeep Goswami^{1

2}, Ritika Khatri³, Bharat Lohiya³, Virendra Singh¹, Rahul Yadav¹, Vinayaka Das¹, Manas Ranjan Tripathy¹, Prabhanjan Dwivedi⁴, Mitul Srivastava⁵, Shailendra Mani³, Shailendra Asthana⁵, Sweety Samal³, Amit Awasthi^{1

2}

Affiliations

¹ Immuno-biology Lab, Infection and Immunology Centre, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, Faridabad, Haryana 121001, India.
² Immunology-Core Lab, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, Faridabad, Haryana 121001, India.
³ Infection and Immunology Centre, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, Faridabad, Haryana 121001, India.
⁴ Small Animal Facility, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, Faridabad, Haryana 121001, India.
⁵ Non-communicable Disease Centre, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, Faridabad, Haryana 121001, India.

Abstract

Effective antiviral drugs are essential to combat COVID-19 and future pandemics. Although many compounds show antiviral in vitro activity, only a few retain effectiveness in vivo against SARS-CoV-2. Here, we show that berbamine (Berb) is effective against SARS-CoV, MER-CoV, SARS-CoV-2 and its variants, including the XBB.1.16 variant. In hACE2.Tg mice, Berb suppresses SARS-CoV-2 replication through two distinct mechanisms: inhibiting spike-mediated viral entry and enhancing antiviral gene expression during infection. The administration of Berb, in combination with remdesivir (RDV), clofazimine (Clof) and fangchinoline (Fcn), nearly eliminated viral load and promoted recovery from acute SARS-CoV-2 infection and its variants. Co-housed mice in direct contact with either pre-treated or untreated infected mice exhibited negligible viral loads, reduced lung pathology, and decreased viral shedding, suggesting that Berb may effectively hinder virus transmission. This broad-spectrum activity positions Berb as a promising preventive or therapeutic option against betacoronaviruses.

Keywords: drugs; health sciences; virology.