Hydroxypropyl-Beta Cyclodextrin Barrier Prevents Respiratory Viral Infections: A Preclinical Study

Area of Science:

• Virology
• Nanotechnology
• Pharmacology

Background:

• Emerging and mutating viruses, including SARS-CoV-2, pose significant global health threats.
• Angiotensin-converting enzyme 2 (ACE2) expression is highest in the nasal airway, indicating it as a primary entry route for SARS-CoV-2.
• Preventative therapies targeting the nasal airway could reduce viral transmission and subsequent pulmonary complications.

Purpose of the Study:

• To assess the safety and antiviral efficacy of cyclodextrin-based formulations.
• To evaluate hydroxypropyl beta-cyclodextrin (HPBCD) and hydroxypropyl gamma-cyclodextrin (HPGCD) for their potential to block viral entry.
• To investigate HPBCD as a potential agnostic barrier against transmissible pathogens.

Main Methods:

• In vitro evaluation of HPBCD and HPGCD using SARS-CoV-2 pseudotypes.
• In vivo efficacy studies using a K18-hACE2 murine model infected with SARS-CoV-2 Delta variant.
• In vitro antiviral testing against lentiviruses, murine hepatitis virus (MHV), and influenza A virus (H1N1).

Main Results:

• HPBCD-based formulations demonstrated significant antiviral effects against SARS-CoV-2 pseudotypes.
• Intranasal pre-treatment with HPBCD reduced viral load and inflammatory signaling in the lungs of infected mice.
• HPBCD exhibited efficacy against multiple viruses, including SARS-CoV-2 variants, MHV, and H1N1.

Conclusions:

• HPBCD-based nasal formulations are safe and effective in reducing viral load and inflammation.
• HPBCD acts as an agnostic barrier, offering potential preventative therapy against a range of transmissible respiratory viruses.
• This approach targets the primary site of viral entry, presenting a novel strategy for infectious disease control.