scholarly journals Drug design of anti-covid19 agents

2020 ◽  
Author(s):  
Pardis Tabaee Damavandi
Keyword(s):  
Drug Design ◽  
Extended Release ◽  
Lung Surfactant ◽  
Antiviral Agents ◽  
Lung Surfactants ◽  
Specific Design ◽  
Site Specific ◽  
Pediatric Use ◽  
The Individual

The first step to drug development that precedes formulation is drug design. In this commentary the specific design of antiviral agents for Covid19 and future viruses, which can be achieved with different strategies, is highlighted. An extended release type of formulation would be ideal for site-specific antivirals however early in vitro or toxicology screening is very important. A lot of preparations are already available to be exploited. Conversely, some are available for pediatric use, i.e lung surfactants, which understandably the supply of is aimed at premature children. New lung surfactant design for adults could however be also incentivised which may help re-establishing autonomous respiration (autonomically mediated) post-covid19 infection of the individual. The surfactants could also help counteract dyspnea which is sometimes a known side effect of antiviral agents.

scholarly journals Design of targeted dosage form of ofloxacin+

2006 ◽  
Vol 71 (12) ◽  
pp. 1269-1273 ◽  
Author(s):  
Yar Shahar ◽  
Ahamed Siddiqui ◽  
Ashraf Ali ◽  
E. Manogran
Keyword(s):  
Drug Design ◽  
Specific Activity ◽  
In Vitro Release ◽  
Polymer Backbone ◽  
Specific Chemical ◽  
Site Specific ◽  
Development Of Resistance ◽  
Quinolone Antibiotics ◽  
New Strategy

The targeted pro-drug is a classical pro-drug design often representing a non-specific chemical approach to mask undesirable drug properties, such as limited bioavailability, lack of site specificity, and chemical instability. On the other hand, targeted pro-drug design represents a new strategy for directed and efficient drug delivery. Quinolone antibiotics exert their pharmacological effect by inhibiting the cell wall synthesis of the pathogen. However, development of resistance exists, which instigates for a new higher congener to remain in clinical practice. To overcome this phenomenon and also to produce site-specific activity of the cell walls of the pathogen, ofloxacin is conjugated with a hydroxypropyl methacrylamide polymer backbone moiety. The results of in vitro release studies indicate the possibilities for the development of a new drug for site-specific therapy with an improved t 1/2 of the drug. This novel pro-drugmay have opened a new vista in antibiotic chemotherapy. .

Mixtures of synthetic peptides and dipalmitoylphosphatidylcholine as lung surfactants

1992 ◽  
Vol 262 (3) ◽  
pp. L292-L300
Author(s):  
L. R. McLean ◽  
J. L. Krstenansky ◽  
R. L. Jackson ◽  
K. A. Hagaman ◽  
K. A. Olsen ◽  
...  
Keyword(s):  
Synthetic Peptides ◽  
Lung Surfactant ◽  
Helical Structure ◽  
Lipid Binding ◽  
Water Soluble ◽  
Lung Model ◽  
Lung Surfactants ◽  
Surfactant Apoprotein

Synthetic peptides that differ in their lipid-peptide interactions were combined with dipalmitoylphosphatidylcholine (DPPC) and tested in an adult rat lavaged lung model in vitro for efficacy as totally synthetic lung surfactants. The putative amphipathic alpha-helical region of the major lung surfactant apoprotein (SP-A81-102), an analogue with increased amphipathic alpha-helical potential ([Lys88,97,Glu99,Trp102]-SP-A81-102]), and the hydrophobic peptide gramicidin D were all ineffective. Three water-soluble lipid-binding peptides that contain amphipathic alpha-helical regions were also tested. Of these, only a 24-residue amphipathic alpha-helical peptide (18As) based on the lipid-binding sequences of the plasma apolipoproteins was effective. Melittin and glucagon were ineffective. Mixtures of 18As and DPPC also restored gas exchange in an in vivo lavaged guinea pig lung model to 90-95% of its prelavage value and maintained it for at least 3 h. Mixtures of DPPC and 18As are also surface active (gamma min less than 4 mN/m in the pulsating bubble). These data demonstrate the efficacy of a combination of a single lipid and a small, water-soluble, nonhemolytic, synthetic peptide containing an amphipathic alpha-helical structure and a sequence unrelated to any of the reported lung surfactant apoprotein sequences.

Formulation and In vitro Release Characterization of Metoprolol Succinate Extended Release Tablets

2012 ◽  
Vol 4 (4) ◽  
pp. 1537-1543
Author(s):  
Sakthikumar T ◽  
Rajendran N N ◽  
Natarajan R
Keyword(s):  
Drug Release ◽  
Extended Release ◽  
In Vitro Release ◽  
Methyl Cellulose ◽  
Wet Granulation ◽  
Direct Compression ◽  
Metoprolol Succinate ◽  
Extended Release Formulations ◽  
Vitro Release

The present study was aimed to develop an extended release tablet of metoprolol Succinate for the treatment of hypertension.  Four extended release formulations F1-F4 were developed using varying proportions of hydroxylpropyl-methylcellulose K100M, sodium carboxy methyl cellulose and Eudragit L30 D55 by wet granulation. Five extended release formulations F5-F9 containing HPMC K100M and HPMC 5 cps in varying concentration were developed by direct compression. The physicochemical and in vitro release characteristics of all the formulations were investigated and compared. Two formulations, F7 and F8 have shown not more 25% drug release  in 1st h, 20%-40% drug release at 4th hour, 40%-60% drug release at 8th hour and not less than 80% at 20th hour and the release pattern conform with USP specification for 24 hours extended release formulation. It can be conclusively stated that optimum concentration of HPMC K100M (58%-65%) by direct compression method can yield an extended release of metoprolol succinate for 24 hours.

Recent Advances towards Drug Design Targeting the Protease of 2019 novel coronavirus (2019-nCoV)

2020 ◽  
Vol 27 ◽  
Author(s):  
Sehrish Bano ◽  
Abdul Hameed ◽  
Mariya Al-Rashida ◽  
Shafia Iftikhar ◽  
Jamshed Iqbal
Keyword(s):  
Drug Design ◽  
Rna Polymerase ◽  
Drug Targets ◽  
Antiviral Agents ◽  
Structural Features ◽  
Antiviral Drugs ◽  
Rna Dependent Rna Polymerase ◽  
Mortality And Morbidity ◽  
Functional Relationships ◽  
Novel Coronavirus

Background: The 2019 novel coronavirus (2019-nCoV), also known as coronavirus 2 (SARS-CoV-2) acute respiratory syndrome has recently emerged and continued to spread rapidly with high level of mortality and morbidity rates. Currently, no efficacious therapy is available to relieve coronavirus infections. As new drug design and development takes much time, there is a possibility to find an effective treatment from existing antiviral agents. Objective: In this case, there is a need to find out the relationship between possible drug targets and mechanism of action of antiviral drugs. This review discusses about the efforts to develop drug from known or new molecules. Methods: Viruses usually have two structural integrities, proteins and nucleic acids, both of which can be possible drug targets. Herein, we systemically discuss the structural-functional relationships of the spike, 3-chymotrypsin-like protease (3CLpro), papain like protease (PLpro) and RNA-dependent RNA polymerase (RdRp), as these are prominent structural features of corona virus. Certain antiviral drugs such as Remdesivir are RNA dependent RNA polymerase inhibitor. It has the ability to terminate RNA replication by inhibiting ATP. Results: It is reported that ATP is involved in synthesis of coronavirus non-structural proteins from 3CLpro and PLpro. Similarly, mechanisms of action of many other antiviral agents has been discussed in this review. It will provide new insights into the mechanism of inhibition, and let us develop new therapeutic antiviral approaches against novel SARS-CoV-2 coronavirus. Conclusion: In conclusion, this review summarizes recent progress in developing protease inhibitors for SARS-CoV-2.

scholarly journals In VitroAnalyses of the Effects of Heparin and Parabens on Candida albicans Biofilms and Planktonic Cells

2011 ◽  
Vol 56 (1) ◽  
pp. 148-153 ◽  
Author(s):  
Marisa H. Miceli ◽  
Stella M. Bernardo ◽  
T. S. Neil Ku ◽  
Carla Walraven ◽  
Samuel A. Lee
Keyword(s):  
Candida Albicans ◽  
Metabolic Activity ◽  
Biofilm Formation ◽  
High Dose ◽  
Dependent Manner ◽  
Planktonic Cells ◽  
Content Type ◽  
Heparin Sodium ◽  
The Individual

ABSTRACTInfections and thromboses are the most common complications associated with central venous catheters. Suggested strategies for prevention and management of these complications include the use of heparin-coated catheters, heparin locks, and antimicrobial lock therapy. However, the effects of heparin onCandida albicansbiofilms and planktonic cells have not been previously studied. Therefore, we sought to determine thein vitroeffect of a heparin sodium preparation (HP) on biofilms and planktonic cells ofC. albicans. Because HP contains two preservatives, methyl paraben (MP) and propyl paraben (PP), these compounds and heparin sodium without preservatives (Pure-H) were also tested individually. The metabolic activity of the mature biofilm after treatment was assessed using XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction and microscopy. Pure-H, MP, and PP caused up to 75, 85, and 60% reductions of metabolic activity of the mature preformedC. albicansbiofilms, respectively. Maximal efficacy against the mature biofilm was observed with HP (up to 90%) compared to the individual compounds (P< 0.0001). Pure-H, MP, and PP each inhibitedC. albicansbiofilm formation up to 90%. A complete inhibition of biofilm formation was observed with HP at 5,000 U/ml and higher. When tested against planktonic cells, each compound inhibited growth in a dose-dependent manner. These data indicated that HP, MP, PP, and Pure-H havein vitroantifungal activity againstC. albicansmature biofilms, formation of biofilms, and planktonic cells. Investigation of high-dose heparin-based strategies (e.g., heparin locks) in combination with traditional antifungal agents for the treatment and/or prevention ofC. albicansbiofilms is warranted.

scholarly journals Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-Cov-2 Infection In Vitro

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 437
Author(s):  
Dean Gilham ◽  
Audrey L. Smith ◽  
Li Fu ◽  
Dalia Y. Moore ◽  
Abenaya Muralidharan ◽  
...  
Keyword(s):  
Antiviral Agents ◽  
Host Cells ◽  
Protein Inhibitor ◽  
Angiotensin Converting Enzyme 2 ◽  
Dipeptidyl Peptidase 4 ◽  
Surface Receptors ◽  
Bet Inhibitor ◽  
Epigenetic Machinery ◽  
Unexplored Area

Effective therapeutics are urgently needed to counter infection and improve outcomes for patients suffering from COVID-19 and to combat this pandemic. Manipulation of epigenetic machinery to influence viral infectivity of host cells is a relatively unexplored area. The bromodomain and extraterminal (BET) family of epigenetic readers have been reported to modulate SARS-CoV-2 infection. Herein, we demonstrate apabetalone, the most clinical advanced BET inhibitor, downregulates expression of cell surface receptors involved in SARS-CoV-2 entry, including angiotensin-converting enzyme 2 (ACE2) and dipeptidyl-peptidase 4 (DPP4 or CD26) in SARS-CoV-2 permissive cells. Moreover, we show that apabetalone inhibits SARS-CoV-2 infection in vitro to levels comparable to those of antiviral agents. Taken together, our study supports further evaluation of apabetalone to treat COVID-19, either alone or in combination with emerging therapeutics.

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