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Background: Cymbopogon martinii (palmrose essential oil, PEO) and Cymbopogon citratus (lemon grass essential oil, (LEO) are used as complementary and traditional medicine worldwide. PEO and LEO from Cymbopogon genus, contains a diversity of pharmacologically active compounds. Due to the complex nature of essential oils, their antifungal mechanism of action against aspergillosis and mucormycosis is still not completely understood. Purpose: Hence, the present study aimed at determining the chemical profile of each PEO and LEO and performing a molecular docking of two of their components geraniol and geranial against fungal enzymes involved in riboflavin synthesis pathway viz: riboflavin synthase (RS), riboflavin biosynthesis protein RibD domain-containing protein (RibD), and 3,4-dihydroxy-2-butanone 4-phosphate synthase (DBPS) as opposite sites for drug designing against aspergillosis and mucormycosis and in vitro confirmation. Study design and method: Chemical profile of PEO and LEO was performed by GC-FID analysis. For molecular docking, patch-dock tool was conducted. Ligand-enzyme 3-D interactions were also calculated. ADMET properties (absorption, distribution, metabolism, excretion and toxicity) were also calculated. Antifungal activity was evaluated agaist three test pathogens Aspergillus niger, Aspergillus oryzae and Mucor indicus using poisoned food technique. Results: GC-FID showed geraniol/geranial as the major components in PEO/LEO, thus, they were selected for docking analysis. Docking analysis specified active binding of geraniol and geranial to riboflavin synthase (RS), riboflavin biosynthesis protein RibD domain-containing protein (RibD), and 3,4-dihydroxy-2-butanone 4-phosphate synthase (DBPS) fungal enzymes. Wet-lab authentication was achieved by three fungal strains A. niger, A. oryzae and M. indicus. Docking studies revealed that the ligands geraniol/geranial exhibited interactions with RS, RibD, and DBPS fungal enzymes by H- bond and hydrophobic interactions. Geraniol and geranial obeyed LIPINSKY rule, and exhibited adequate bioactivity. Wet lab results indicated that PEO/LEO was able to inhibit fungal growth against test pathogens. Conclusions: These findings confirm the fungicidal properties PEO/LEO essential oils as possible alternatives to synthetic fungicides. © 2023 The Author(s)
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Introduction Entry factors angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) facilitate Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) entry into the host cells. Despite SARS-CoV-2s preference for respiratory system, extra-pulmonary organ involvement has been suggested. Recent studies report that SARS-CoV-2 leads to direct hepatic impairment in COVID-19 patients, necessitating further investigations about hepatic involvement. ACE2 and TMPRSS2 are expressed in primary human hepatocytes (PHH), suggesting a possible susceptibility to SARS-CoV-2. Despite this, data on infection and factors modulating functional regulation of SARS-CoV-2 infection in PHH are lacking. MicroRNAs (miRNAs) are approximately 22 nucleotide-long non-coding RNAs that have been shown to regulate various cellular processes including virus-host interactions. We aimed to study the susceptibility of PHH to SARS-CoV-2 and to evaluate the potential of miRNAs in modulating viral infection. Materials and methods We investigated the role of miRNAs to regulate SARS-CoV-2 infection in PHH in vitro. To strengthen our fndings, we analysed liver autopsies from COVID-19 patients. Results We demonstrate that PHH can be readily infected with SARS-CoV-2, resulting in robust replication and sustained host responses as indicated by the upregulation of several interferon-stimulated genes. In silico analyses unravelled miR-200c-3p, miR-429 and miR-141-3p as candidate miRNAs targeting ACE2 and, let-7c-5p targeting TMPRSS2. Expression of these miRNAs reduced SARS-CoV-2 infection in PHH. Furthermore, expression of several endogenous miRNAs was altered upon SARS-CoV-2 infection in PHH and human liver autopsies. Conclusion Our results show that PHH are susceptible towards SARS-CoV-2 and cellular miRNAs can diminish SARS-CoV-2 viral burden.
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SARS-CoV-2 (COVID-19) caused more than 15 % mortality worldwide. Spike (S) protein has recently been regarded as a suitable target for drug design. The present in silico docking study was designed to evaluate the effect of potent bioactive molecule citral present in essential oils of lemon grass plant leaves against Spike (S) protein from SARS-CoV-2. Till date there is no work is undertaken on in-silico analysis of these compounds against Spike (S) protein of SARS-CoV-2. In the present study, GC-FID (gas chromatography with flame-ionization detection) based aroma profile, molecular docking studies were conducted by using Patchdock analysis. Protein Interactions Calculator was used for protein interactions. In-silico absorption, distribution, metabolism, excretion and toxicity (ADMET) profile was also studied. GC-FID revealed citral as major compound in lemon grass oil. The calculated parameters such as docking score indicated effective binding of citral to COVID-19 S-protein. Interactions results indicated that, Spike (S) protein/citral complexes forms hydrophobic interactions. In-silico absorption, distribution, metabolism, excretion and toxicity (ADMET) studies provided guidelines and mechanistic scope for identification of potent anti-COVID 19 drug. Therefore, essential oil from lemon grass may represent potential herbal treatment to act as COVID-19 Spike (S) protein inhibitor. © 2022, Moroccan Institute of Scientific and Technical Information. All rights reserved.
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SARS-CoV-2 (COVID-19)-associated co-infections like "Aspergillosis", has recently baffled the world. Due to its key role in cell wall synthesis, in the present study UDP-glycosyltransferase, glucosamine-6-phosphate synthase and chitin synthase have been chosen as appropriate targets for molecular docking. The objective of the present study was molecular docking of eucalyptus essential oil component 1,8 cineole against cell wall enzymes followed by in vitro validation. For molecular docking, patch-dock web based online tool was used. Ligand-Protein 2D and 3D Interactions were also studied. Drug likeliness, toxicity profile and cancer cell line toxicity were also studied. Molecular docking results indicated that 1,8 cineole form hydrogen bonding and hydrophobic interactions with UDP-glycosyltransferase, glucosamine-6-phosphate synthase and chitin synthase enzymes. 1,8 cineole also depicted drug likeliness by showing compliance with the LIPINSKY rule, sufficient level of bioactivity and cancer cell line toxicity thus signifying its role as a potent anti-fungal drug.
ABSTRACT
SARS-CoV-2 spreading its tentacles across the world as a major world pandemic. There is a race to develop suitable drug drugs and vaccines for this disease. Due to lack ofdrug drugs s at present, various anti-HIV drug drugs s have been repurposed. Due to its vital role in virus replication, Spike (S) protein has recently been regarded as a suitable target for drug drugs design. With an urgent and key need for safe and effective drugs to combat this disease, we have explored 12 bioactive compounds from eucalyptus oil against Spike (S) protein from SARS-CoV-2. SWISS-MODEL was used for homology modeling. Molecular docking studies were conducted by using Patch dock analysis. Protein Interactions Calculator was used for protein interactions. Pharmacokinetics and Insilico ADMET profile (absorption, distribution, metabolism, excretion and toxicity) was also studied. Docking score showed effective binding of all bioactive molecules especially Toruatone to COVID-19 S-protein. Interactions results indicated that Spike (S) protein / Toruatone complexes forms hydrogen and hydrophobic interactions. Insilico absorption, distribution, metabolism, excretion and toxicity (ADMET) studies provided guidelines and mechanistic scope for identification of potent anti-COVID 19 drugs. This study highlights the potential of existing bioactive components from essential oil from eucalyptus to act as anti-COVID-19drug drugs. © 2021, Moroccan Institute of Scientific and Technical Information. All rights reserved.
ABSTRACT
SARS-CoV-2 (COVID-19), member of corona virus family, is a positive single stranded RNA virus. Due to lack of drugs it is spreading its tentacles across the world. Being associated with cough, fever, and respiratory distress, this disease caused more than 15% mortality worldwide. Mpro/3CLpro has recently been regarded as a suitable target for drug design due to its vital role in virus replication. The current study focused on the inhibitory activity of eucalyptol (1,8 cineole), an essential oil component from eucalyptus oil, against Mpro/3CLprofrom SARS-CoV-2. Till date there is no work is undertaken on in-silico analysis of this compound against Mpro/3CLproof SARS-CoV-2. Molecular docking studies were conducted by using 1-click dock tool and Patchdock analysis. In-silico absorption, distribution, metabolism, excretion and toxicity (ADMET) profile were also studied. The calculated parameters such as docking score indicated effective binding of eucalyptol to COVID-19 Mpro protein. Active site prediction revealed the involvement of active site residues in ligand binding. Interactions results indicated that, Mpro/3CLpro/eucalyptol complexes forms hydrophobic interactions. ADMET studies provided guidelines and mechanistic scope for identification of potent anti-COVID 19 drug. Therefore, eucalyptol may represent potential herbal treatment to act as COVID-19 Mpro/3CLproinhibitor, a finding which must be validated in vivo. © 2020 Articles by the authors;SHST, Cluj-Napoca, Romania. All Rights Reserved.
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Objective: To identify major phenotypes of neurologic manifestations and their prevalence in hospitalized patients infected with severe acute respiratory syndrome corona virus disease 2019 (COVID-19). Background: Emerging evidence suggests COVID-19 presentation is not limited to the respiratory system but may have multi-organ involvement including dysfunctions of the nervous system. However, little is known about the major phenotypes, prevalence, and impact of nervous system involvement on patient outcomes. Design/Methods: We are the coordinating center and part of the GCS-Neuro COVID consortium tier 1 pragmatic study. We prospectively screened 127 consecutive patients admitted to a large academic hospital from 03/22/2020 to 09/05/2020. Adults age ≥ 18 years old admitted to the hospital with suspected or confirmed COVID19 infection were included. Eight patients met exclusion criteria of severe pre-existing baseline neurologic dysfunction such as coma or vegetative state that limit detection of new or worsening neurologic symptoms. Results: Of the total cohort of 119 patients (mean age 63.4 years, 48% women), 73 (61.3%) exhibited new/worsening neurologic symptoms. The most common phenotype was acute encephalopathy (44%), followed by headache (40%), abnormal smell/taste (23%), and new movement abnormalities (21%). Other neurologic manifestations included clinical or electrographic seizures (10%), coma (4%), and intracerebral hemorrhage (3%). Neurologic symptoms began an average of 6.2 days after respiratory symptoms (range 0 to 48), although 2 patients developed neurologic symptoms before respiratory symptoms. COVID-19 patients with neurologic symptoms were less likely to have a favorable outcome at discharge (24.6%) with mRS (0-1) compared to those without neurological symptoms (61.9%). Conclusions: Neurologic manifestations in patients infected with COVID-19 are prevalent and have significant impact on patient outcomes at acute hospital discharge in this single-center study. Further studies are underway to better characterize neurologic symptoms as well as follow-up to determine the long-term impact of COVID-19 on patient outcome and recovery.
ABSTRACT
Across the world, COVID-19, a positive single-stranded RNA virus member of corona virus family, is spreading its tentacles due to lack of drugs at present causing 15% mortality worldwide due to cough, fever and respiratory problems cause more than. Due to its vital role in polyprotein processing necessary for coronavirus reproduction, the main viral proteinase (Mpro/3CLpro) has recently been regarded as a suitable target for drug design against SARS infection. The present in silico docking study was designed to evaluate the effect of potent 12 bioactive molecules present in essential oils of eucalyptus plant leaves. In the present study, molecular docking studies were conducted using a 1-click dock. Docked complex analysis was carried out using the Biovia Discovery studio, Chimera and VMD tools. Active sites were obtained from CAST P analysis. The calculated parameters such as RMSD, docking score indicated effective binding of bioactive essential oil molecules, especially Jensenone, to COVID-19 proteinase. Active site prediction further validated the role of active site residues in ligand binding. Molecular interactions results indicated that Mpro/eucalyptol complexes form hydrophobic interactions, hydrogen bond interactions and strong ionic interactions. Therefore, eucalyptus essential oil bioactive compounds may represent potential treatment potential to act as COVID-19 Mpro inhibitor. However, further research is necessary to investigate their potential medicinal use.