Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
1.
J Blood Med ; 12: 505-515, 2021.
Article in English | MEDLINE | ID: covidwho-1302063

ABSTRACT

INTRODUCTION: Coronaviruses belong to a large family that leads to respiratory infection of various severity. Hematological ratios are indicators of inflammatory response widely used in viral pneumonia with affordability in developing countries. PURPOSE: Study the role of the neutrophil lymphocyte ratio (NLR), derived NLR ratio (d-NLR), platelet lymphocyte ratio (PLR), and lymphocyte monocyte ratio (LMR) in predicting the outcome of COVID-19 Egyptian patients. METHODS: A retrospective study on 496 COVID-19 Egyptian patients, managed in four tertiary centers, grouped into non-severe, severe, and critical. Patients' laboratory assessment including total leucocyte count (TLC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute monocyte count (AMC), NLR, d-NLR, LMR and, PLR were reported as well as C reactive protein (CRP), D-dimer and serum ferritin. RESULTS: TLC, ANC, AMC, NLR, d-NLR and, PLR were highest in the critical group (p<0.001 for all except AMC p=0.033), while this group had the least ALC and LMR (p=0.049 and <0.001, respectively). Higher CRP and d-dimer levels were reported in the critical group (p<0.001). At the same time, higher ferritin was found in the severe group more than the critical and non-severe groups (p<0.001, p=0.005, respectively). We calculated the optimal cut-off values of the hematological ratio; NLR (3.5), d-NLR (2.86), PLR (192), and LMR (3). D-NLR had the highest specificity (89.19%), while NLR had the highest sensitivity (71.38%). By univariate logistic regression, age, DM, HTN, cardiovascular diseases, COPD, NLR, d-NLR, LMR and PLR, CRP, steroid, oxygen aids, and mechanical ventilation were associated with the severity of COVID-19. Still, only age, NLR, CRP, and oxygen aid were independent predictors in multivariate logistic regression. CONCLUSION: NLR is a predictor for severity in COVID-19. LMR, d-NLR, and PLR may assist in risk stratification.

2.
Struct Chem ; 32(4): 1415-1430, 2021.
Article in English | MEDLINE | ID: covidwho-1028481

ABSTRACT

Recently, the SARS-CoV-2 (COVID-19) pandemic virus has been spreading throughout the world. Until now, no certified drugs have been discovered to efficiently inhibit the virus. The scientists are struggling to find new safe bioactive inhibitors of this deadly virus. In this study, we aim to find antagonists that may inhibit the activity of the three major viral targets: SARS-CoV-2 3-chymotrypsin-like protease (6LU7), SARS-CoV-2 spike protein (6VYB), and a host target human angiotensin-converting enzyme 2 (ACE2) receptor (1R42), which is the entry point for the viral encounter, were studied with the prospects of identifying significant drug candidate(s) against COVID-19 infection. Then, the protein stability produced score of less than 0.6 for all residues of all studied receptors. This confirmed that these receptors are extremely stable proteins, so it is very difficult to unstable the stability of these proteins through utilizing individual drugs. Hence, we studied the combination and tricombination therapy between bioactive compounds which have the best binding affinity and some antiviral drugs like chloroquine, hydroxychloroquine, azithromycin, simeprevir, baloxavir, lopinavir, and favipiravir to show the effect of combination and tricombination therapy to disrupt the stability of the three major viral targets that are mentioned previously. Also, ADMET study suggested that most of all studied bioactive compounds are safe and nontoxic compounds. All results confirmed that caulerpin can be utilized as a combination and tricombination therapy along with the studied antiviral drugs for disrupting the stability of the three major viral receptors (6LU7, 6VYB, and 1R42). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11224-020-01723-5.

3.
J Environ Sci Health A Tox Hazard Subst Environ Eng ; 55(11): 1373-1386, 2020.
Article in English | MEDLINE | ID: covidwho-808183

ABSTRACT

This work aimed at evaluating the inhibitory effect of ten natural bioactive compounds (1-10) as potential inhibitors of SARS-CoV-2-3CL main protease (PDB ID: 6LU7) and SARS-CoV main proteases (PDB IDs: 2GTB and 3TNT) by molecular docking analysis. The inhibitory effect of all studied compounds was studied with compared to some proposed antiviral drugs which currently used in COVID-19 treatment such as chloroquine, hydroxychloroquine, azithromycin, remdesivir, baloxvir, lopinavir, and favipiravir. Homology modeling and sequence alignment was computed to evaluate the similarity between the SARS-CoV-2-3CL main protease and other SARS-CoV receptors. ADMET properties of all studied compounds were computed and reported. Also, molecular dynamic (MD) simulation was performed on the compound which has the highest binding affinity inside 6LU7 obtained from molecular docking analysis to study it is stability inside receptor in explicit water solvent. Based on molecular docking analysis, we found that caulerpin has the highest binding affinity inside all studied receptors compared to other bioactive compounds and studied drugs. Our homology modeling and sequence alignment showed that SARS-CoV main protease (PDB ID: 3TNT) shares high similarity with 3CLpro (96.00%). Also, ADMET properties confirmed that caulerpin obeys Lipinski's rule and passes ADMET property, which make it a promising compound to act as a new safe natural drug against SARS-CoV-2-3CL main protease. Finally, MD simulation confirmed that the complex formed between caulerpin and 3CLpro is stable in water explicit and had no major effect on the flexibility of the protein throughout the simulations and provided a suitable basis for our study. Also, binding free energy between caulerpin and 6LU7 confirmed the efficacy of the caulerpin molecule against SARS-CoV-2 main protease. So, this study suggested that caulerpin could be used as a potential candidate in COVID-19 treatment.


Subject(s)
Betacoronavirus/drug effects , Betacoronavirus/enzymology , Cysteine Endopeptidases/metabolism , Indoles/pharmacology , Viral Nonstructural Proteins/metabolism , Coronavirus 3C Proteases , Molecular Docking Simulation , Molecular Dynamics Simulation , SARS-CoV-2
4.
Struct Chem ; : 1-22, 2020 Jul 23.
Article in English | MEDLINE | ID: covidwho-669618

ABSTRACT

Presently, the SARS-CoV-2 (COVID-19) pandemic has been spreading throughout the world. Some drugs such as lopinavir, simeprevir, hydroxychloroquine, chloroquine, and amprenavir have been recommended for COVID-19 treatment by some researchers, but these drugs were not effective enough against this virus. This study based on in silico approaches was aimed to increase the anti-COVID-19 activities of these drugs by using caulerpin and its derivatives as an adjunct drug against SARS-CoV-2 receptor proteins: the SARS-CoV-2 main protease and the SARS-CoV-2 spike protein. Caulerpin exhibited antiviral activities against chikungunya virus and herpes simplex virus type 1. Caulerpin and some of its derivatives showed inhibitory activity against Alzheimer's disease. The web server ANCHOR revealed higher protein stability for the two receptors with disordered score (< 0.6). Molecular docking analysis showed that the binding energies of most of the caulerpin derivatives were higher than all the suggested drugs for the two receptors. Also, we deduced that inserting NH2, halogen, and vinyl groups can increase the binding affinity of caulerpin toward 6VYB and 6LU7, while inserting an alkyl group decreases the binding affinity of caulerpin toward 6VYB and 6LU7. So, we can modify the inhibitory effect of caulerpin against 6VYB and 6LU7 by inserting NH2, halogen, and vinyl groups. Based on the protein disordered results, the SARS-CoV-2 main protease and SARS-CoV-2 spike protein domain are highly stable proteins, so it is quite difficult to unstabilize their integrity by using individual drugs. Also, molecular dynamics (MD) simulation indicates that binding of the combination therapy of simeprevir and the candidate studied compounds to the receptors was stable and had no major effect on the flexibility of the protein throughout the simulations and provided a suitable basis for our study. So, this study suggested that caulerpin and its derivatives could be used as a combination therapy along with lopinavir, simeprevir, hydroxychloroquine, chloroquine, and amprenavir for disrupting the stability of SARS-CoV2 receptor proteins to increase the antiviral activity of these drugs.

SELECTION OF CITATIONS
SEARCH DETAIL