Drug eruption: A mimicker of Coronavirus disease-2019 rash

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infections can be associated with several cutaneous lesions, among which maculopapular rash is the most common. A maculopapular rash can also be induced by medications used for Coronavirus disease-2019 (COVID-19) treatment. The distinction between viral rash and drug eruption may be difficult especially in case of several medication use for COVID-19. Thus, this study aimed to describe cutaneous manifestations in six patients with COVID-19 and highlight clues for distinguishing SARS-CoV-2-related rash and drug eruption. Between March and June 2020, 1,492 patients were hospitalized for COVID-19 and treated with hydroxychloroquine in Marmara University Hospital. Among them, six cases were consulted for possible COVID-19-related rash or drug reaction. Hydroxychloroquine was given as monotherapy in one patient. All six patients developed an erythematous, symmetrical, and maculopapular eruption that mainly affected the trunk, axilla, and genitocrural region, 5-21 days after the onset of COVID-19 symptoms. Five patients developed rash in 4-11 days after treatment completion. Pruritus was severe. All were treated with topical corticosteroids and oral antihistamines, which provided partial relief. The resolution of the eruption was typically slow, which took a few weeks. A long period between the COVID-19 symptoms and the eruption, as well as slow recovery, is in favor of drug eruption. The effects of co-existent viral infection, a well-known promoting drug eruption factor, in facilitating adverse drug reaction in patients with COVID-19 needs further observations and research. © 2022 Istanbul Assoc. of Dermatology and Venerology. All rights reserved.

Drug eruption: A mimicker of Coronavirus disease-2019 rash

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infections can be associated with several cutaneous lesions, among which maculopapular rash is the most common. A maculopapular rash can also be induced by medications used for Coronavirus disease-2019 (COVID-19) treatment. The distinction between viral rash and drug eruption may be difficult especially in case of several medication use for COVID-19. Thus, this study aimed to describe cutaneous manifestations in six patients with COVID-19 and highlight dues for distinguishing SARS-CoV-2-related rash and drug eruption. Between March and June 2020, 1,492 patients were hospitalized for COVID-19 and treated with hydroxychloroquine in Marmara University Hospital. Among them, six cases were consulted for possible COVID-19-related rash or drug reaction. Hydroxychloroquine was given as monotherapy in one patient. All six patients developed an erythematous, symmetrical, and maculopapular eruption that mainly affected the trunk, axilla, and genitocrural region, 5-21 days after the onset of COVID-19 symptoms. Five patients developed rash in 4-11 days after treatment completion. Pruritus was severe. All were treated with topical corticosteroids and oral antihistamines, which provided partial relief. The resolution of the eruption was typically slow, which took a few weeks. A long period between the COVID-19 symptoms and the eruption, as well as slow recovery, is in favor of drug eruption. The effects of co-existent viral infection, a well-known promoting drug eruption factor, in facilitating adverse drug reaction in patients with COVID-19 needs further observations and research.

MOLECULAR DOCKING AND SCREENING OF DRUGS FOR 6LU7 PROTEASE INHIBITOR AS A POTENTIAL TARGET FOR COVID-19

Objective: The aim of present investigation is docking of various existing antiviral, anti-tubercular and anti-malarial drugs on 6LU7 receptor of SARS-CoV-2 in the treatment of COVID-19. Methods: In this study, the structure of coronavirus binding protein and ligands for various drugs were collected from the protein data bank and pub chem. Molecular docking was carried out using Schrodinger 9.0 software. In molecular docking study, 19 different drugs of various categories like antiviral, anti-malarial and anti-tubercular were investigated for analyzing binding to 6LU7 receptors of COVID-19. Results: The docking result showed a high affinity of zanamivir, montelukast, ramdesvir, ritonavir, cobicistat and favipravir to the 6LU7 receptor of novel coronavirus. Thus the combination of these drugs may be useful in preventing further infection and can be used as a potential target for further in vitro and in vivo studies of SARS-CoV-2. Conclusion: Treatment of COVID-19 has been challenge due to the non-availability of effective drug therapy. In this study, we reported drugs for targeting 6LU7 Mpro/3Clpro protein, which showed prominent effects as potential inhibitors of COVID-19 Mpro. © 2022 The Authors. Published by Innovare Academic Sciences Pvt Ltd.

A review on synthetic account of 1,2,4-oxadiazoles as anti-infective agents.

Most of the currently marketed drugs consist of heterocyclic scaffolds containing nitrogen and or oxygen as heteroatoms in their structures. Several research groups have synthesized diversely substituted 1,2,4-oxadiazoles as anti-infective agents having anti-bacterial, anti-viral, anti-leishmanial, etc. activities. For the first time, the present review article will provide the coverage of synthetic account of 1,2,4-oxadiazoles as anti-infective agents along with their potential for SAR, activity potential, promising target for mode of action. The efforts have been made to provide the chemical intuitions to the reader to design new chemical entity with potential of anti-infective activity. This review will mark the impact as the valuable, comprehensive and pioneered work along with the library of synthetic strategies for the organic and medicinal chemists for further refinement of 1,2,4-oxadiazole as anti-infective agents.

The journey of antimalarial drugs against SARS-CoV-2: Review article.

The recent outbreak of coronavirus pandemic (COVID-19) introduced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has greatly affected the global public health. This pandemic disease became particularly threatening after the start of a new wave. Vaccines of tested efficacy to stop COVID-19 infection are being investigated vigorously worldwide. Currently, some specific drugs have been authorized for COVID-19, but the improvement of antivirals requires time. Hence, a faster way of treatment is done by drug repurposing. Repurposing of drugs is promising for treating and reducing the symptoms of the disease, and it a fast, easy, and safe method to address the crisis, because of their previously known applications. Some antimalarial drugs, especially chloroquine and hydroxychloroquine, have been repurposed, as they exhibited promising results in vitro and in vivo. This article investigates repurposed antimalarial drugs, focusing on their antiviral mechanisms of action, effects in combinations, trial results, and their side effects.

Anti-malarial Drugs are Not Created Equal for SARS-CoV-2 Treatment: A Computational Analysis Evidence.

BACKGROUND: The evolution of the pandemic has burdened the national healthcare systems worldwide and at present, there is no preferred antiviral treatment for COVID-19. Recently, the SARS-Cov-2 protease structure was released that may be exploited in in-silico studies in order to conduct molecular docking analysis. METHODS: In particular, we compared the binding of twoantimalarial drugs, already in use, (i.e. chloroquine and hydroxychloroquine), which showed some potential clinical effects on COVID-19 patients, using ritonavir, lopinavir and darunavir as positive control tree antiviral recognized compounds. RESULTS: Our results showed that hydroxychloroquine but not chloroquine exhibited a significant binding activity to the main protease similar to that possessed by protease inhibitors tested for other viral infections. CONCLUSION: Our data suggest that hydroxychloroquine may exert additional direct antiviral activity compared to chloroquine. In the absence of clinical studies comparing the efficacy of these two compounds, hydroxychloroquine may offer additional effects and may be considered as the first choice.

Chloroquine kills hair cells in zebrafish lateral line and murine cochlear cultures: Implications for ototoxicity.

Hearing and balance deficits have been reported during and following treatment with the antimalarial drug chloroquine. However, experimental work examining the direct actions of chloroquine on mechanoreceptive hair cells in common experimental models is lacking. This study examines the effects of chloroquine on hair cells using two common experimental models: the zebrafish lateral line and neonatal mouse cochlear cultures. Zebrafish larvae were exposed to varying concentrations of chloroquine phosphate or hydroxychloroquine for 1 h or 24 h, and hair cells assessed by antibody staining. A significant, dose-dependent reduction in the number of surviving hair cells was seen across conditions for both exposure periods. Hydroxychloroquine showed similar toxicity. In mouse cochlear cultures, chloroquine damage was specific to outer hair cells in tissue from the cochlear basal turn, consistent with susceptibility to other ototoxic agents. These findings suggest a need for future studies employing hearing and balance monitoring during exposure to chloroquine and related compounds, particularly with interest in these compounds as therapeutics against viral infections including coronavirus.

Molecular docking and dynamic simulations for antiviral compounds against SARS-CoV-2: A computational study.

The aim of this study was to develop an appropriate anti-viral drug against the SARS-CoV-2 virus. An immediately qualifying strategy would be to use existing powerful drugs from various virus treatments. The strategy in virtual screening of antiviral databases for possible therapeutic effect would be to identify promising drug molecules, as there is currently no vaccine or treatment approved against COVID-19. Targeting the main protease (pdb id: 6LU7) is gaining importance in anti-CoV drug design. In this conceptual context, an attempt has been made to suggest an in silico computational relationship between US-FDA approved drugs, plant-derived natural drugs, and Coronavirus main protease (6LU7) protein. The evaluation of results was made based on Glide (Schrödinger) dock score. Out of 62 screened compounds, the best docking scores with the targets were found for compounds: lopinavir, amodiaquine, and theaflavin digallate (TFDG). Molecular dynamic (MD) simulation study was also performed for 20 ns to confirm the stability behaviour of the main protease and inhibitor complexes. The MD simulation study validated the stability of three compounds in the protein binding pocket as potent binders.