Diltiazem inhibits SARS-CoV-2 cell attachment and internalization and decreases the viral infection in mouse lung

Abstract

The continuous emergence of severe acute respiratory coronavirus 2 (SARS-CoV-2) variants and the increasing number of breakthrough infection cases among vaccinated people support the urgent need for research and development of antiviral drugs. Viral entry is an intriguing target for antiviral drug development. We found that diltiazem, a blocker of the L-type calcium channel Cav1.2 pore-forming subunit (Cav1.2 α1c) and an FDA-approved drug, inhibits the binding and internalization of SARS-CoV-2, and decreases SARS-CoV-2 infection in cells and mouse lung. Cav1.2 α1c interacts with SARS-CoV-2 spike protein and ACE2, and affects the attachment and internalization of SARS-CoV-2. Our finding suggests that diltiazem has potential as a drug against SARS-CoV-2 infection and that Cav1.2 α1c is a promising target for antiviral drug development for COVID-19.

Galectin-9 protects humanized-ACE2 immunocompetent mice from SARS-CoV-2 infection

“…Our data is relatively equivalent to that of viral burdens of rh-gal9 treated animals of influenza infected animals ( 20 ). Additionally, consistent to other therapeutics tested in K18-hACE2 mice, viral burdens were reduced in groups that exhibited increase survival frequency compared to controls ( 31 – 34 ).…”

Integrative network pharmacology and in silico analyses identify the anti-omicron SARS-CoV-2 potential of eugenol

“…The results indicated that these target genes of eugenol highly enriched in the biological processes, pathways of human diseases and SARS-CoV-2 pathway (e.g. Ca2 + signaling) [ 128 ], including complement and coagulation cascades, calcium signaling pathway, viral infection, and cancers. The SymMap symptoms manifested that eugenol was significantly associated to headache and pain, and some neurological symptoms, upper respiratory tract symptoms, and gastrointestinal symptoms.…”

Transferrin Receptor Protein 1 Cooperates with mGluR2 To Mediate the Internalization of Rabies Virus and SARS-CoV-2

“…Several cellular proteins have been reported to affect the entry of viruses. For example, the L-type calcium channel Ca v 1.2 pore-forming subunit is an entry factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus ( 9 , 10 ); GRP78 is an entry factor for Japanese encephalitis virus ( 11 ), and Coxsackievirus ( 12 ); and TIM-1 is an entry factor for Chikungunya virus and hepatitis C virus ( 13 , 14 ). Identifying novel conserved entry factors and exploring the underlying mechanisms are essential to develop broad-spectrum antiviral drugs that block early infection.…”