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1.
J Biomol Struct Dyn ; : 1-19, 2022 Apr 21.
Article in English | MEDLINE | ID: covidwho-1805902

ABSTRACT

COVID-19 patients have shown overexpressed serum levels of several pro-inflammatory cytokines, leading to a high mortality rate due to numerous complications. Also, previous studies demonstrated that the metronidazole (MTZ) administration reduced pro-inflammatory cytokines and improved the treatment outcomes for inflammatory disorders. However, the effect and mechanism of action of MTZ on cytokines have not been studied yet. Thus, the current study aimed to identify anti-cytokine therapeutics for the treatment of COVID-19 patients with cytokine storm. The interaction of MTZ with key cytokines was investigated using molecular docking studies. MTZ-analogues, and its structurally similar FDA-approved drugs were also virtually screened against interleukin-12 (IL-12). Moreover, their mechanism of inhibition regarding IL-12 binding to IL-12 receptor was investigated by measuring the change in volume and area. IL-12-metronidazole complex is found to be more stable than all other cytokines under study. Our study also revealed that the active sites of IL-12 are inhibited from binding to its target, IL-12 receptor, by modifying the position of the methyl and hydroxyl functional groups in MTZ. Three MTZ analogues, metronidazole phosphate, metronidazole benzoate, 1-[1-(2-Hydroxyethyl)-5-nitroimidazol-2-yl]-N-methylmethanimine-oxide, and two FDA-approved drugs acyclovir (ACV), and tetrahydrobiopterin (THB) were also found to prevent binding of IL-12 to IL-12 receptor similar to MTZ by changing the surface and volume of IL-12 upon IL-12-drug/ligand complex formation. According to the RMSD results, after 100 ns MD simulations of human IL-12-MTZ/ACV/THB drug complexes, it was also observed that each complex was swinging within a few Å compared to their corresponding docking poses, indicating that the docking poses were reliable. The current study demonstrates that three FDA-approved drugs, namely, metronidazole, acyclovir and tetrahydrobiopterin, are potential repurposable treatment options for overexpressed serum cytokines found in COVID-19 patients. Similar approach is also useful to develop therapeutics against other human disorders.

2.
Cureus ; 14(2): e21854, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1776597

ABSTRACT

Herpes esophagitis is common among immunocompromised hosts but is relatively rare among immunocompetent patients. Its symptoms are vague because many different symptoms can be induced by esophageal lesions. Here, we report a case of herpes esophagitis in an elderly immunocompetent patient. A 91-year-old woman visited our community hospital with a complaint of appetite loss for several days. Although she did not have any symptoms of epigastric, oral, or retrosternal pain, multiple ulcers were detected in her esophagus. Biopsy of the edge of the ulcer showed giant cells, indicating a herpes virus infection. She was diagnosed with herpes esophagitis and treated with acyclovir for one week. Her symptoms completely resolved after treatment, and she was discharged. Herpes esophagitis can manifest as vague symptoms in immunocompetent elderly patients. Therefore, herpes esophagitis must be considered in the differential diagnosis of elderly patients presenting with vague symptoms.

3.
Revista Cubana de Medicina Militar ; 50(4), 2021.
Article in Spanish | Scopus | ID: covidwho-1772404

ABSTRACT

Introduction: SARS-CoV-2 virus, responsible for COVID-19, has a high contagion rate and is capable of producing conditions at different levels in the body, and includes the central nervous system, with manifestations such as febrile and afebrile seizures, status epilepticus, encephalopathies and encephalitis. Objective: To describe a patient with encephalopathy, as a form of presentation of COVID-19. Clinical case: A 25-year-old patient with a history of post-traumatic obstructive hydrocephalus, with ventricular peritoneal shunt, positive for COVID-19, who developed neurological manifestations, in the absence of respiratory manifestations. He was treated according to the protocol for patients with COVID-19, anti-cerebral edema measures and use of the CIGB-258 peptide. The patient had a favorable evolution towards recovery Conclusions: In patients with encephalopathy of unknown cause, in the context of the COVID-19 pandemic, SARS-CoV-2 infection should be considered. The evolution can be favorable with the use of general measures and anti-cerebral edema. © 2021, Editorial Ciencias Medicas. All rights reserved.

4.
Journal of Pharmaceutical Research International ; 33(54B):321-336, 2021.
Article in English | Web of Science | ID: covidwho-1579785

ABSTRACT

The objectives of the study were to examine the virtual screening of the compounds and sigma-covalent inhibition of SARS-CoV-2 RdRp (RNA-Dependent RNA-Polymerase), which is conserved and is an essential enzyme for RNA transcription and replication of this virus. In this study, we collected around 1225 similar compounds of Penciclovir and Acyclovir inhibitors from PubChem and predicted ADME (Adsorption, Distribution, Metabolism and Excretion) molecular descriptors using Swiss-ADME server. Virtually screened 24/1225 compounds based on drug-likeliness five rules (Lipinski, Ghose, Veber, Egan, and Muegge) and lead-likeliness properties. Further 10/24 compounds screened, based on high binding affinity and RMSD<3.5 angstrom against RdRp structure using PyRx docking software. Furthermore, the molecular interactions of 10 compounds studied using Discovery studio software and finally screened five PubChem compounds 57201841, 135408972, 54552823, 135409422 and 467850, based on bioactivity score using Molinsipiration cheminformatics software. All these five compounds showed up anti-SARS CoV-2 activity, though further in-vitro studies are required.

5.
Frontiers in Materials ; 8:6, 2021.
Article in English | Web of Science | ID: covidwho-1560794

ABSTRACT

The ongoing COVID-19 pandemic caused by SARS-CoV-2 has significantly affected the world, creating a global health emergency. For controlling the virus spread, effective and reliable diagnostic and therapeutic measures are highly expected. Using proper biomedical materials to produce detection kits/devices and personal protective equipment (PPE), such as swabs and masks, has become the focus since they play critical roles in virus diagnostics and prevention. Electrospun polymer composites have garnered substantial interest due to their potential to provide antiviral healthcare solutions. In this review, we summarized the recent efforts in developing advanced antiviral electrospun polymer composites for virus detection and prevention. We highlighted some novel strategies for developing effective antiviral personal protective equipment (PPE), including self-sterilization, reusability, and potential antiviral drug encapsulation. Besides, we discussed the current challenges and future perspectives for improving the materials' performance to achieve better virus detection, antiviral, prevention, and therapeutics.

6.
Pharmaceutics ; 13(10)2021 Sep 27.
Article in English | MEDLINE | ID: covidwho-1480912

ABSTRACT

In recent years, the application of solid foams has become widespread. Solid foams are not only used in the aerospace field but also in everyday life. Although foams are promising dosage forms in the pharmaceutical industry, their usage is not prevalent due to decreased stability of the solid foam structure. These special dosage forms can result in increased bioavailability of drugs. Low-density floating formulations can also increase the gastric residence time of drugs; therefore, drug release will be sustained. Our aim was to produce a stable floating formula by foaming. Matrix components, PEG 4000 and stearic acid type 50, were selected with the criteria of low gastric irritation, a melting range below 70 °C, and well-known use in oral drug formulations. This matrix was melted at 54 °C in order to produce a dispersion of active substance and was foamed by different gases at atmospheric pressure using an ultrasonic homogenizer. The density of the molded solid foam was studied by the pycnometer method, and its structure was investigated by SEM and micro-CT. The prolonged drug release and mucoadhesive properties were proved in a pH 1.2 buffer. According to our experiments, a stable foam could be produced by rapid homogenization (less than 1 min) without any surfactant material.

7.
Molecules ; 26(13)2021 Jun 22.
Article in English | MEDLINE | ID: covidwho-1288957

ABSTRACT

In the current work, a simple, economical, accurate, and precise HPLC method with UV detection was developed to quantify Favipiravir (FVIR) in spiked human plasma using acyclovir (ACVR) as an internal standard in the COVID-19 pandemic time. Both FVIR and ACVR were well separated and resolved on the C18 column using the mobile phase blend of methanol:acetonitrile:20 mM phosphate buffer (pH 3.1) in an isocratic mode flow rate of 1 mL/min with a proportion of 30:10:60 %, v/v/v. The detector wavelength was set at 242 nm. Maximum recovery of FVIR and ACVR from plasma was obtained with dichloromethane (DCM) as extracting solvent. The calibration curve was found to be linear in the range of 3.1-60.0 µg/mL with regression coefficient (r2) = 0.9976. However, with acceptable r2, the calibration data's heteroscedasticity was observed, which was further reduced using weighted linear regression with weighting factor 1/x. Finally, the method was validated concerning sensitivity, accuracy (Inter and Intraday's % RE and RSD were 0.28, 0.65 and 1.00, 0.12 respectively), precision, recovery (89.99%, 89.09%, and 90.81% for LQC, MQC, and HQC, respectively), stability (% RSD for 30-day were 3.04 and 1.71 for LQC and HQC, respectively at -20 °C), and carry-over US-FDA guidance for Bioanalytical Method Validation for researchers in the COVID-19 pandemic crisis. Furthermore, there was no significant difference for selectivity when evaluated at LLOQ concentration of 3 µg/mL of FVIR and relative to the blank.


Subject(s)
Amides/analysis , Amides/blood , Antiviral Agents/analysis , Antiviral Agents/blood , Biological Assay/methods , COVID-19/drug therapy , Chromatography, High Pressure Liquid/methods , Liquid-Liquid Extraction/methods , Pyrazines/analysis , Pyrazines/blood , Acyclovir/analysis , Acyclovir/blood , COVID-19/blood , Calibration , Drug Stability , Freezing , Humans , Reference Standards , Reproducibility of Results , Solvents/chemistry
8.
Cureus ; 13(4): e14476, 2021 Apr 13.
Article in English | MEDLINE | ID: covidwho-1234918

ABSTRACT

Encephalitis is one of the rare complications of coronavirus disease 2019 (COVID-19) that can be missed and confused with other causes of encephalitis. There was a 36-year-old male known to have glucose-6 phosphate dehydrogenase deficiency, who was brought to the emergency department with fever and confusion of one-week duration. Altered mental status work-up, including cerebrospinal fluid analysis, was done and turned out to be nondiagnostic. Multiple prolonged video-electroencephalographic recordings were done and showed different abnormalities suggestive of encephalitis. The diagnosis of COVID-19-induced encephalitis was made by exclusion of other encephalitis-related etiologies in the presence of a positive COVID-19 polymerase chain reaction (PCR) test, and treatment was initiated accordingly. Over a period of three weeks, the patient showed progressive improvement and was discharged home with regular follow-up in the neurology clinic. Upon follow-up in the clinic, the patient was fully independent but with multiple abnormal electroencephalographic recordings showing generalized encephalopathy with no epileptic discharges.

9.
Int J Mol Sci ; 21(17)2020 Aug 20.
Article in English | MEDLINE | ID: covidwho-725538

ABSTRACT

At the moment, there are no U.S. Food and Drug Administration (U.S. FDA)-approved drugs for the treatment of COVID-19, although several antiviral drugs are available for repurposing. Many of these drugs suffer from polymorphic transformations with changes in the drug's safety and efficacy; many are poorly soluble, poorly bioavailable drugs. Current tools to reformulate antiviral APIs into safer and more bioavailable forms include pharmaceutical salts and cocrystals, even though it is difficult to classify solid forms into these regulatory-wise mutually exclusive categories. Pure liquid salt forms of APIs, ionic liquids that incorporate APIs into their structures (API-ILs) present all the advantages that salt forms provide from a pharmaceutical standpoint, without being subject to solid-state matter problems. In this perspective article, the myths and the most voiced concerns holding back implementation of API-ILs are examined, and two case studies of API-ILs antivirals (the amphoteric acyclovir and GSK2838232) are presented in detail, with a focus on drug property improvement. We advocate that the industry should consider the advantages of API-ILs which could be the genesis of disruptive innovation and believe that in order for the industry to grow and develop, the industry should be comfortable with a certain element of risk because progress often only comes from trying something different.


Subject(s)
Acyclovir/chemistry , Antiviral Agents/chemistry , Betacoronavirus/drug effects , Butyrates/chemistry , Chrysenes/chemistry , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Acyclovir/pharmacology , Antiviral Agents/pharmacology , Biological Availability , Butyrates/pharmacology , COVID-19 , Chemistry, Pharmaceutical/methods , Chrysenes/pharmacology , Drug Repositioning/methods , Humans , Ionic Liquids/chemistry , Pandemics , Pentacyclic Triterpenes , SARS-CoV-2 , Solubility
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