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Full-Text Articles in Medicine and Health Sciences
Discovering New Potential Inhibitors To Sars-Cov-2 Rna Dependent Rna Polymerase (Rdrp) Using High Throughput Virtual Screening And Molecular Dynamics Simulations., Dylan Brunt, Phillip M Lakernick, Chun Wu
Discovering New Potential Inhibitors To Sars-Cov-2 Rna Dependent Rna Polymerase (Rdrp) Using High Throughput Virtual Screening And Molecular Dynamics Simulations., Dylan Brunt, Phillip M Lakernick, Chun Wu
Faculty Scholarship for the College of Science & Mathematics
RNA dependent RNA polymerase (RdRp), is an essential in the RNA replication within the life cycle of the severely acute respiratory coronavirus-2 (SARS-CoV-2), causing the deadly respiratory induced sickness COVID-19. Remdesivir is a prodrug that has seen some success in inhibiting this enzyme, however there is still the pressing need for effective alternatives. In this study, we present the discovery of four non-nucleoside small molecules that bind favorably to SARS-CoV-2 RdRp over the active form of the popular drug remdesivir (RTP) and adenosine triphosphate (ATP) by utilizing high-throughput virtual screening (HTVS) against the vast ZINC compound database coupled with extensive …
Inhibition Of Sars-Cov-2 Wild-Type (Wuhan-Hu-1) And Delta (B.1.617.2) Strains By Marine Sulfated Glycans, Rohini Dwivedi, Poonam Sharma, Marwa Farrag, Seon Beom Kim
Inhibition Of Sars-Cov-2 Wild-Type (Wuhan-Hu-1) And Delta (B.1.617.2) Strains By Marine Sulfated Glycans, Rohini Dwivedi, Poonam Sharma, Marwa Farrag, Seon Beom Kim
Faculty and Student Publications
The Coronavirus disease pandemic has steered the global therapeutic research efforts toward the discovery of potential anti-severe acute respiratory syndrome coronavirus (SARS-CoV-2) molecules. The role of the viral spike glycoprotein (S-protein) has been clearly established in SARS-CoV-2 infection through its capacity to bind to the host cell surface heparan sulfate proteoglycan (HSPG) and angiotensin-converting enzyme-2. The antiviral strategies targeting these 2 virus receptors are currently under intense investigation. However, the rapid evolution of the SARS-CoV-2 genome has resulted in numerous mutations in the S-protein posing a significant challenge for the design of S-protein-targeted inhibitors. As an example, the 2 key …
Pharmacologic Ascorbic Acid As Early Therapy For Hospitalized Patients With Covid-19: A Randomized Clinical Trial, Dagan Coppock, Pierre-Christian Violet, Gustavo Vasquez, Katherine Belden, Michael Foster, Bret Mullin, Devon Magee, Isabelle Mikell, Lokesh Shah, Victoria Powers, Brian Curcio, Daniel A. Monti, Mark Levine
Pharmacologic Ascorbic Acid As Early Therapy For Hospitalized Patients With Covid-19: A Randomized Clinical Trial, Dagan Coppock, Pierre-Christian Violet, Gustavo Vasquez, Katherine Belden, Michael Foster, Bret Mullin, Devon Magee, Isabelle Mikell, Lokesh Shah, Victoria Powers, Brian Curcio, Daniel A. Monti, Mark Levine
Department of Pharmacology and Experimental Therapeutics Faculty Papers
Despite the widespread availability of effective vaccines, new cases of infection with severe acute respiratory syndrome coronavirus-2, the cause of coronavirus disease 2019 (COVID-19), remain a concern in the settings of vaccine hesitancy and vaccine breakthrough. In this randomized, controlled, phase 2 trial, we hypothesized that high-dose ascorbic acid delivered intravenously to achieve pharmacologic concentrations may target the high viral phase of COVID-19 and thus improve early clinical outcomes. Sixty-six patients admitted with COVID-19 and requiring supplemental oxygen were randomized to receive either escalating doses of intravenous ascorbic acid plus standard of care or standard of care alone. The demographic …
Preliminary Research On A Covid-19 Test Strategy To Guide Quarantine Interval In University Students, Jill M. Kolesar, Tyler Gayheart, Lance Poston, Eric Monday, Derek Forster, Elizabeth Belcher, Rani Jaiswal, J. Kirsten Turner, Donna K. Arnett, Eric B. Durbin, Joseph Monroe, Frank Romanelli, Susanne M. Arnold, C. Darrell Jennings, Heidi Weiss, Robert Dipaola
Preliminary Research On A Covid-19 Test Strategy To Guide Quarantine Interval In University Students, Jill M. Kolesar, Tyler Gayheart, Lance Poston, Eric Monday, Derek Forster, Elizabeth Belcher, Rani Jaiswal, J. Kirsten Turner, Donna K. Arnett, Eric B. Durbin, Joseph Monroe, Frank Romanelli, Susanne M. Arnold, C. Darrell Jennings, Heidi Weiss, Robert Dipaola
Pharmacy Practice and Science Faculty Publications
Following COVID-19 exposure, the Centers for Disease Control (CDC) recommends a 10–14-day quarantine for asymptomatic individuals and more recently a 7-day quarantine with a negative PCR test. A university-based prospective cohort study to determine if early polymerase chain reaction (PCR) negativity predicts day 14 negativity was performed. A total of 741 asymptomatic students in quarantine was screened and 101 enrolled. Nasopharyngeal swabs were tested on days 3 or 4, 5, 7, 10, and 14, and the proportion of concordant negative results for each day versus day 14 with a two-sided 95% exact binomial confidence interval was determined. Rates of concordant …
Safety And Pharmacokinetics Of Intranasally Administered Heparin, Hannah M. Harris, Katherine L. Boyet, Hao Liu, Rohini Dwivedi
Safety And Pharmacokinetics Of Intranasally Administered Heparin, Hannah M. Harris, Katherine L. Boyet, Hao Liu, Rohini Dwivedi
Faculty and Student Publications
Purpose: Intranasally administered unfractionated heparin (UFH) and other sulfated polysaccharides are potential prophylactics for COVID-19. The purpose of this research was to measure the safety and pharmacokinetics of clearance of intranasally administered UFH solution from the nasal cavity. Methods: Double-blinded daily intranasal dosing in C57Bl6 mice with four doses (60 ng to 60 μg) of UFH was carried out for fourteen consecutive days, with both blood coagulation measurements and subject adverse event monitoring. The pharmacokinetics of fluorescent-labeled UFH clearance from the nasal cavity were measured in mice by in vivo imaging. Intranasal UFH at 2000 U/day solution with nasal spray …
Inhibitory Effect Of Phytochemicals Towards Sars-Cov-2 Papain Like Protease (Plpro) Proteolytic And Deubiquitinase Activity, Anasha Kawall, Devin S M Lewis, Avini Sharma, Krishna Chavada, Rahul Deshmukh, Srujana Rayalam, Vicky Mody, Shashidharamurthy Taval
Inhibitory Effect Of Phytochemicals Towards Sars-Cov-2 Papain Like Protease (Plpro) Proteolytic And Deubiquitinase Activity, Anasha Kawall, Devin S M Lewis, Avini Sharma, Krishna Chavada, Rahul Deshmukh, Srujana Rayalam, Vicky Mody, Shashidharamurthy Taval
PCOM Scholarly Papers
Recent studies have shown that RNA-dependent RNA polymerase (RdRp), 3-chymotrypsin-like protease (3CLpro), and papain-like protease (PLpro) are necessary for SARS-CoV-2 replication. Among these three enzymes, PLpro exhibits both proteolytic and deubiquitinase (DUB) activity and is responsible for disrupting the host's innate immune response against SARS-CoV-2. Because of this unique property of PLpro, we investigated the inhibitory effects of phytochemicals on the SARS-CoV-2 PLpro enzyme. Our data indicates that the phytochemicals such as catechin, epigallocatechin gallate (EGCG), mangiferin, myricetin, rutin, and theaflavin exhibited inhibitory activity with IC50 values of 14.2, 128.4, 95.3, 12.1, and 43.4, and 7.3 μM, respectively, towards …