Neelam Holkar - Academia.edu (original) (raw)

Papers by Neelam Holkar

AIMS Public Health

NV-CoV-2 is a nanoviricide that is covalently bonded with polyethylene glycol (PEG) and alkyl pen... more NV-CoV-2 is a nanoviricide that is covalently bonded with polyethylene glycol (PEG) and alkyl pendants. This molecular design is used to attack many strains of coronaviruses in a broad-spectrum manner. The ligand works by competitive inhibition and binds to the same site on the S-protein of SARS-CoV that attaches to the cognate cellular receptor, ACE2. This prevents SARS-CoV from binding and infecting the cell. NV-CoV-2 is designed to bind to the free virion particles at multiple points encapsulate the virus and disable its ability to infect the cells. The multi-point binding interaction, like a nano-velcro-tape, may lead to lipid-lipid fusion of the alkyl chains in the nanoviricide micelle with the lipid envelope of the virus. The virus becomes dismantled to a capsid form before the host immune system becomes involved. This putative mechanism is orthogonal to many other anti-coronavirus agents in development. Thus, it maybe possible to produce a stronger antiviral effect when combi...

So far, there are seven coronaviruses identified that infect humans and only 4 of them belong to ... more 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.N...

Remdesivir (RDV) is the only antiviral drug so far approved for COVID-19 therapy by the FDA. Howe... more Remdesivir (RDV) is the only antiviral drug so far approved for COVID-19 therapy by the FDA. However its efficacy is limited in vivo due to its low stability in presence of plasma. This paper compared the stability of RDV encapsulated with our platform technology based polymer NV-387 (NV-CoV-2), in presence of plasma in vitro and in vivo. Furthermore, a non- clinical pharmacology studies of NV-CoV-2 (Polymer) and NV-CoV-2-R (Polymer encapsulated Remdesivir) in both NL-63 infected and uninfected rats were done. In an in vitro cell culture model experiment, antiviral activity of NV-CoV-2 and NV-CoV-2-R are also compared with RDV.The results are (i) NV-CoV-2 polymer encapsulation protects RDV from plasma- mediated catabolism in vitro and in vivo, too. (ii) 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. (iii) NL-63 infected rats body weights and their survival length were like ...

Recent Developments in Medicine and Medical Research Vol. 13, 2021

Frontiers in Nanotechnology

NV-CoV-2, a nanoviricide composed of covalently attached polyethylene glycol and alkyl pendants t... more NV-CoV-2, a nanoviricide composed of covalently attached polyethylene glycol and alkyl pendants that are designed to bind free virion particles of multiple strains of coronaviruses in a broad-spectrum manner at multiple points. The binding interaction is like a nano-velcro-tape and may cause a lipid–lipid fusion between nanoviricide micelle and the lipid envelope of the virus. A nanoviricide can encapsulate the virus and dismantle it without any involvement of the host immune system, ultimately disabling the infectibility of the host cells. Thus, it may be expected to count a stronger and synergistic antiviral effect by combining NV-CoV-2 with other anti-coronavirus regimens like remdesivir. Furthermore, some ligands similar to the SARS-CoV S-protein are designed by molecular modeling and attached to the nanoviricide at the same site as where the cognate cellular receptor, ACE2, binds. As a result, a competitive binding inhibition may occur. A nanoviricide can encapsulate other anti...

Integrative Molecular Medicine

Human coronaviruses (HCoVs) cause respiratory diseases infecting the upper and/or lower respirato... more Human coronaviruses (HCoVs) cause respiratory diseases infecting the upper and/or lower respiratory tract. The six human coronaviruses so far identified are HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU-1, SARS-CoV, and MERS-CoV. Four of these coronaviruses (HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU-1) are known as circulating common coronavirus found continuously in the human population causing mostly common cold, with few cases of severe diseases. In late December 2019, a novel human coronavirus, now called SARS-CoV-2, was identified during an outbreak in Wuhan, China. The disease spectrum caused by this virus is now called COVID-19 (Coronavirus Infectious disease 2019). This novel coronavirus has spread globally resulting in a worldwide pandemic that continues to rage as of now. SARS-CoV-2 has a high case morbidity and mortality rate and is high risk to the elderly populations, immune-compromised populations, and to those who have other critical issues like heart disease, diabetes, etc. In this review, we summarize the latest information of the epidemiology, pathogenesis, and clinical aspects of SARS-CoV-2, and discuss the current scientific and therapeutic advancements for clinical treatment of this pandemic novel coronavirus. A: Human Coronavirus and its Different Types: Coronaviruses (CoVs) are single-stranded positive-sense RNA viruses whose genome (>27kb) is encapsulated within a lipid membrane envelope carrying spike protein [15]. This envelope is studded with glycoprotein spikes that give coronaviruses their crown

AIMS Public Health

NV-CoV-2 is a nanoviricide that is covalently bonded with polyethylene glycol (PEG) and alkyl pen... more NV-CoV-2 is a nanoviricide that is covalently bonded with polyethylene glycol (PEG) and alkyl pendants. This molecular design is used to attack many strains of coronaviruses in a broad-spectrum manner. The ligand works by competitive inhibition and binds to the same site on the S-protein of SARS-CoV that attaches to the cognate cellular receptor, ACE2. This prevents SARS-CoV from binding and infecting the cell. NV-CoV-2 is designed to bind to the free virion particles at multiple points encapsulate the virus and disable its ability to infect the cells. The multi-point binding interaction, like a nano-velcro-tape, may lead to lipid-lipid fusion of the alkyl chains in the nanoviricide micelle with the lipid envelope of the virus. The virus becomes dismantled to a capsid form before the host immune system becomes involved. This putative mechanism is orthogonal to many other anti-coronavirus agents in development. Thus, it maybe possible to produce a stronger antiviral effect when combi...

So far, there are seven coronaviruses identified that infect humans and only 4 of them belong to ... more 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.N...

Remdesivir (RDV) is the only antiviral drug so far approved for COVID-19 therapy by the FDA. Howe... more Remdesivir (RDV) is the only antiviral drug so far approved for COVID-19 therapy by the FDA. However its efficacy is limited in vivo due to its low stability in presence of plasma. This paper compared the stability of RDV encapsulated with our platform technology based polymer NV-387 (NV-CoV-2), in presence of plasma in vitro and in vivo. Furthermore, a non- clinical pharmacology studies of NV-CoV-2 (Polymer) and NV-CoV-2-R (Polymer encapsulated Remdesivir) in both NL-63 infected and uninfected rats were done. In an in vitro cell culture model experiment, antiviral activity of NV-CoV-2 and NV-CoV-2-R are also compared with RDV.The results are (i) NV-CoV-2 polymer encapsulation protects RDV from plasma- mediated catabolism in vitro and in vivo, too. (ii) 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. (iii) NL-63 infected rats body weights and their survival length were like ...

Recent Developments in Medicine and Medical Research Vol. 13, 2021

Frontiers in Nanotechnology

NV-CoV-2, a nanoviricide composed of covalently attached polyethylene glycol and alkyl pendants t... more NV-CoV-2, a nanoviricide composed of covalently attached polyethylene glycol and alkyl pendants that are designed to bind free virion particles of multiple strains of coronaviruses in a broad-spectrum manner at multiple points. The binding interaction is like a nano-velcro-tape and may cause a lipid–lipid fusion between nanoviricide micelle and the lipid envelope of the virus. A nanoviricide can encapsulate the virus and dismantle it without any involvement of the host immune system, ultimately disabling the infectibility of the host cells. Thus, it may be expected to count a stronger and synergistic antiviral effect by combining NV-CoV-2 with other anti-coronavirus regimens like remdesivir. Furthermore, some ligands similar to the SARS-CoV S-protein are designed by molecular modeling and attached to the nanoviricide at the same site as where the cognate cellular receptor, ACE2, binds. As a result, a competitive binding inhibition may occur. A nanoviricide can encapsulate other anti...

Integrative Molecular Medicine

Human coronaviruses (HCoVs) cause respiratory diseases infecting the upper and/or lower respirato... more Human coronaviruses (HCoVs) cause respiratory diseases infecting the upper and/or lower respiratory tract. The six human coronaviruses so far identified are HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU-1, SARS-CoV, and MERS-CoV. Four of these coronaviruses (HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU-1) are known as circulating common coronavirus found continuously in the human population causing mostly common cold, with few cases of severe diseases. In late December 2019, a novel human coronavirus, now called SARS-CoV-2, was identified during an outbreak in Wuhan, China. The disease spectrum caused by this virus is now called COVID-19 (Coronavirus Infectious disease 2019). This novel coronavirus has spread globally resulting in a worldwide pandemic that continues to rage as of now. SARS-CoV-2 has a high case morbidity and mortality rate and is high risk to the elderly populations, immune-compromised populations, and to those who have other critical issues like heart disease, diabetes, etc. In this review, we summarize the latest information of the epidemiology, pathogenesis, and clinical aspects of SARS-CoV-2, and discuss the current scientific and therapeutic advancements for clinical treatment of this pandemic novel coronavirus. A: Human Coronavirus and its Different Types: Coronaviruses (CoVs) are single-stranded positive-sense RNA viruses whose genome (>27kb) is encapsulated within a lipid membrane envelope carrying spike protein [15]. This envelope is studded with glycoprotein spikes that give coronaviruses their crown