Rhamnolipid Nano-Micelles Inhibit SARS-CoV-2 Infection and Have No Dermal or Eye Toxic Effects in Rabbits
Abstract
:1. Introduction
2. Results
2.1. Production of Rhamnolipids
2.2. Preparation and Characterization of Rhamnolipids Nano-Micelles
2.3. Antiviral Activity of Rhamnolipids Nano-Micelles
2.4. Irritation and Skin Sensitization Test
2.4.1. Skin Irritation Test
2.4.2. Eye Irritation Test
2.4.3. Skin Sensitization Test
2.4.4. Histopathological and Immunohistochemical Evaluations
2.5. Biochemical Analysis
2.6. Hematological Examination
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Methodology
4.2.1. Production of Rhamnolipids
4.2.2. Preparation of Rhamnolipids Nano-Micelles
4.2.3. Characterization of Rhamnolipids Nano-Micelles
Particle Size and Zeta Potential
Transmission Electron Microscopy
Determination of pH
4.2.4. SARS-CoV-2 Infection Experiments (HCoV-19/England/2/202 Strain)
4.2.5. Irritation and Skin Sensitization Study
Animal
Eye Irritation Test
Skin Irritation Test
Skin Sensitization Test
Histopathological and Immunohistochemical Evaluations
Biochemical Analysis
Hematological Examination
4.2.6. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Control Site | Treated Site | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Erythema and Eschar | Edema | Erythema and Eschar | Edema | ||||||||||||||
Intact | Abraded | Intact | Abraded | Intact | Abraded | Intact | Abraded | ||||||||||
Tested sample/tested time (h) | Animal Number | 24 | 72 | 24 | 72 | 24 | 72 | 24 | 72 | 24 | 72 | 24 | 72 | 24 | 72 | 24 | 72 |
Rhamnolipids nano-micelles (0.625 µg/mL) | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
PBS (10 mM, pH 7.4) | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Tested Solution | Tissues Examined in the Eye | Number of Rabbits | |||||
---|---|---|---|---|---|---|---|
1 | 2 | 3 | |||||
RT. Untreated | LT. Treated | RT. Untreated | LT. Treated | RT. Untreated | LT. Treated | ||
Rhamnolipids nano-micelles (0.625 mg/mL) | Cornea | 0 | 0 | 0 | 0 | 0 | 0 |
Iris | 0 | 0 | 0 | 0 | 0 | 0 | |
Conjunctiva | 0 | 0 | 0 | 0 | 0 | 0 | |
PBS (10 mM, pH 7.4) | Cornea | 0 | 0 | 0 | 0 | 0 | 0 |
Iris | 0 | 0 | 0 | 0 | 0 | 0 | |
Conjunctiva | 0 | 0 | 0 | 0 | 0 | 0 |
Hours/ Number of Animals | Positive Control Erythema/Edema | Rhamnolipids Nano-Micelles (0.625 mg/mL) Erythema/Edema | Negative Control Erythema/Edema | ||||||
---|---|---|---|---|---|---|---|---|---|
24 | 48 | 72 | 24 | 48 | 72 | 24 | 48 | 72 | |
1 | 0/0 | 2/1 | 2/2 | 0/0 | 0/0 | 0/0 | 0/0 | 0/0 | 0/0 |
2 | 0/0 | 2/1 | 2/2 | 0/0 | 0/0 | 0/0 | 0/0 | 0/0 | 0/0 |
3 | 0/0 | 2/1 | 2/3 | 0/0 | 0/0 | 0/0 | 0/0 | 0/0 | 0/0 |
4 | 0/0 | 3/1 | 2/3 | 0/0 | 0/0 | 0/0 | 0/0 | 0/0 | 0/0 |
5 | 0/0 | 3/1 | 3/3 | 0/0 | 0/0 | 0/0 | 0/0 | 0/0 | 0/0 |
6 | 0/0 | 0/0 | |||||||
7 | 0/0 | 0/0 | |||||||
8 | 0/0 | 0/0 | |||||||
9 | 0/0 | 0/0 | |||||||
10 | 0/0 | 0/0 |
Animal Group | AST (U/L) | ALT (U/L) |
---|---|---|
Untreated animal (Negative Control) | 30.00 ± 1.53 | 27.33 ± 1.20 |
PBS | 32.70 ± 3.20 | 28.20 ± 2.80 |
Rhamnolipids nano-micelles (0.625 mg/mL) | 35.00 ± 4.35 | 28.67 ± 3.71 |
Animal Groups | PCV (%) | Hb (g/dL) | RBCs × 106/µL | MCV (fL) | MCHC (%) |
---|---|---|---|---|---|
Untreated animal (Control) | 38.53 ± 0.56 | 12.00 ± 0.64 | 8.84 ± 0.11 | 48.87±0.22 | 37.26 ± 0.46 |
PBS | 37.90 ± 0.61 | 11.51 ± 0.32 | 7.80 ± 0.13 | 48.20 ± 0.19 | 37.3 ± 0.32 |
Rhamnolipids nano-micelles (0.625 mg/mL) | 39.41± 0.26 | 11.34 ± 0.20 | 7.61±0.140 | 47.72 ± 0.26 | 37.28 ± 0.34 |
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Ali, A.M.; Hill, H.J.; Elkhouly, G.E.; Bakkar, M.R.; Raya, N.R.; Stamataki, Z.; Abo-zeid, Y. Rhamnolipid Nano-Micelles Inhibit SARS-CoV-2 Infection and Have No Dermal or Eye Toxic Effects in Rabbits. Antibiotics 2022, 11, 1556. https://doi.org/10.3390/antibiotics11111556
Ali AM, Hill HJ, Elkhouly GE, Bakkar MR, Raya NR, Stamataki Z, Abo-zeid Y. Rhamnolipid Nano-Micelles Inhibit SARS-CoV-2 Infection and Have No Dermal or Eye Toxic Effects in Rabbits. Antibiotics. 2022; 11(11):1556. https://doi.org/10.3390/antibiotics11111556
Chicago/Turabian StyleAli, Alaa M., Harriet J. Hill, Gehad E. Elkhouly, Marwa Reda Bakkar, Nermeen R. Raya, Zania Stamataki, and Yasmin Abo-zeid. 2022. "Rhamnolipid Nano-Micelles Inhibit SARS-CoV-2 Infection and Have No Dermal or Eye Toxic Effects in Rabbits" Antibiotics 11, no. 11: 1556. https://doi.org/10.3390/antibiotics11111556