TaffiX® Nasal Powder forms an Effective Barrier against SARS-CoV-2

TaffiXÂ® is a personal anti-viral nasal powder that is commercially available in Israel and Europe...


Introduction
Effective measures that reduce exposure to the SARS-CoV-2 virus are an important aspect of containing the COVID-19 pandemic. With uncertainties surrounding the emergence of new variants and vaccine protection, and evidence that presymptomatic and asymptomatic transmission of SARS-CoV-2 are significant factors contributing to spread of infections [1], there is a need for mechanisms that can reduce exposure to the virus. The cellular entry of SARS-CoV-2 depends on the binding of the spike (S) protein to a specific cellular receptor, angiotensin-converting enzyme 2 (ACE2), and subsequent S protein processing by cellular proteases [2]. ACE2 and other proteases are highly expressed in ciliated and goblet nasal cells, which supports the growing understanding that nasal infection is the dominant route of transfection for COVID-19 viruses and therefore protection of the nasal epithelium is an effective means of controlling infection [3,4].
Hou et al. describe the "infection gradient" whereby SARS-CoV-2 shows a gradient infectivity from the proximal to distal respiratory tract, with ciliated airway cells and AT-2 cells as primary targets for SARS-CoV-2 infection [5]. The authors conclude that the nasal epithelium is an important gateway and therefore its protection could dramatically decrease the risk of viral infection and transmission. TaffiX ® , a nasal hydroxypropyl methylcellulose (HPMC) based powder spray, is a semisynthetic, inert, viscoelastic muco-adhesive polymer used frequently in the pharmaceutical industry. HPMC is used in eye drops, as an excipient and controlleddelivery component in oral medications, and found in a variety of commercial products including several nasal powder products used as prevention of allergy [6,7]. Polymer-based powder formulations show no adhesion until their absorption of mucus occurs on the nasal mucosa surface. This allows easy application to the nasal cavity by nasal insufflation even if the polymer is highly mucoadhesive [8].
TaffiX ® creates an acidic gel (pH 3.5) once it has reached the nasal mucosa thus creating a local hostile microenvironment to viruses at a pH range known to be associated with viral death [9].
TaffiX ® also contains benzalkonium chloride which is known as an antimicrobial preservative and was shown by Chin et al. to inactivate SARS-CoV-2 [10]. This study we report that TaffiX ® was able to form a protective barrier against SARS-CoV-2 virus using experimental in vitro conditions that reduced the titer of recoverable live virus, as well as viral RNA by 99%.

TaffiX ® Assay
One hundred-fifty µl of sterile water was added to individual sterile 40 μm cell strainers (BiologGLX) in the wells of a 6 well plate. Twenty mg TaffiX ® was added and mixed with the water with a pipet tip until homogeneous across the cell strainer surface, and incubated at room temperature for 10 min. Ten μl of virus, (10,000 PFUs of Hong Kong/VM20, BEI Resources), was added to the center of each cell strainer and incubated at room temperature for another 10 min. The bottoms of the cell strainers were washed with 500 µl serum-free DMEM and flow through was collected for RNA isolation and plaque assays.

Plaque Assay
Plaque assays were performed as described in [11]. Vero

Taffix ® Gel formation in Pig Noses
The Taffix ® powder (4 puffs per nostril, parallel to 1 puff per human nostril as indicated in product instructions) was sprayed on a fresh slices of pig nasal cavity, obtained from a meat processing

Results
To test whether the TaffiX ® can form a protective barrier against SARS-CoV-2, a gel of TaffiX   To test the stability of the gel pH on nasal tissue ex vivo, the powder was sprayed on a fresh slices of pig nasal cavity soaked in saline solution and placed covered in an oven at 34°C to resemble the human nose conditions and clinical dose per surface area.
The gel formation time, and gel appearance during 6 hrs were monitored as well as gel pH. TaffiX ® powder formed a uniform gel on a pig nasal cavity tissue within 1 min from spray and was stable as a gel film for 6 hrs. The initial pH of the gel was 3.6 and the final (after 6 hours) pH was 4.4.

Discussion
Under in vitro conditions, TaffiX ® formed a protective barrier against SARS-COV-2. Although these are artificial conditions, ex vivo experiments with pig nasal tissue demonstrated that a TaffiX ® gel is formed within 1 minute from spray and an acidic film is maintained on the tissue for at least 5 hours. Without the gel protection, the human nasal mucosal pH is approximately 5.5-6.5 [12], which is a comfortable environment to SARS-CoV-2 virus. Clinical study by Hull et al. demonstrated in a randomized, double blind, placebocontrolled study that irrigation with an acidic nasal hydrogel spray reduced the severity and duration of the common cold symptoms [13]. TaffiX ® is a safe and easy to use powder that may provide a straightforward mechanism to reduce infections and thus the spread of COVID-19.

Funding
This work was supported by Nasus Pharma, Tel Aviv, Israel.

Footnote
TaffiX ® is approved in Israel (Amar: 33010001) with the following Indication for Use: TaffiX ® is intended for use to block inhaled viruses and bacteria within the nasal cavity. TaffiX ® is legally marketed in Europe (CE-DE/CA09/0760/N18/001) with the following Indication for Use: TaffiX ® is indicated for use as a protective mechanical barrier against allergens and viruses (e.g., SARS-CoV-2) within the nasal cavity.