RT Journal Article
SR Electronic
T1 Nanoviricide’s platform technology based NV-CoV-2 polymer increases the half-life of Remdesivir in vivo
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.17.468980
DO 10.1101/2021.11.17.468980
A1 Ashok Chakraborty
A1 Anil Diwan
A1 Vinod Arora
A1 Yogesh Thakur
A1 Vijetha Chiniga
A1 Jay Tatake
A1 Preetam Holkar
A1 Neelam Holkar
A1 Bethany Pond
YR 2021
UL http://biorxiv.org/content/early/2021/11/19/2021.11.17.468980.abstract
AB 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 StatementThe authors have declared no competing interest.NVNanoviricidesPK/PDPharmacokinetics/ PharmacodynamicsRDVRemdesivirNV-387Nanoviricides-Polymer 387NV-387-RNanoviricides-Polymer 387-Remdesivir conjugateSBECDCommercial encapsulating agent SBECD (GILEAD)SBECD-RCommercial Remdesivir conjugated with SBECDPBSPhosphate Buffered SalineDMSODimethyl SulfoxideRPLRat PlasmaMeOHMethanolADMEAbsorption, Distribution, Metabolism and ExcretionSDStandard Deviation