Abstract
So far, there are seven coronaviruses identified that infect humans and only 4 of them belong to the beta family of coronavirus (HCoV-HKU1, SARS-CoV-2, MERS-CoV and SARS-CoV). SARS family are known to cause severe respiratory disease in humans. In fact, SARS-CoV-2 infection caused a pandemic COVID-19 disease with high morbidity and mortality. Remdesivir (RDV) is the only antiviral drug so far approved for COVID-19 therapy by the FDA. However, the efficacy of RDV in vivo is limited due to its low stability in presence of plasma. This is the report of analysis of the non-clinical pharmacology study of NV-CoV-2 (Polymer) and NV-CoV-2-R (Polymer encapsulated Remdesivir) in both infected and uninfected rats with SARS-CoV-2.
Detection and quantification of NV-CoV-2-R in plasma samples was done by MS-HPLC chromatography analyses of precipitated plasma samples from rat subjects.
NV-CoV-2-R show RDV peak in MS-HPLC chromatography, whereas only NV-CoV-2 does not show any RDV-Peak, as expected.
NV-CoV-2 polymer encapsulation protects RDV in vivo from plasma-mediated catabolism.
Body weight measurements of the normal (uninfected) rats after administration of the test materials (NV-CoV-2, and NV-CoV-2-R) show no toxic effects on them.
Our platform technology based NV-387-encapsulated-RDV (NV-CoV-2-R) drug has a dual effect on coronaviruses. First, NV-CoV-2 itself as an antiviral regimen. Secondly, RDV is protected from plasma-mediated degradation in transit, rendering altogether the safest and an efficient regimen against COVID-19.
Competing Interest Statement
The authors have declared no competing interest.
LIST OF ABBREVIATIONS
- NV
- Nanoviricides
- PK/PD
- Pharmacokinetics/ Pharmacodynamics
- RDV
- Remdesivir
- NV-387
- Nanoviricides-Polymer 387
- NV-387-R
- Nanoviricides-Polymer 387-Remdesivir conjugate
- SBECD
- Commercial encapsulating agent SBECD (GILEAD)
- SBECD-R
- Commercial Remdesivir conjugated with SBECD
- PBS
- Phosphate Buffered Saline
- DMSO
- Dimethyl Sulfoxide
- RPL
- Rat Plasma
- MeOH
- Methanol
- ADME
- Absorption, Distribution, Metabolism and Excretion
- SD
- Standard Deviation