Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 23
Filter
1.
Curr Pharm Des ; 2022 Mar 22.
Article in English | MEDLINE | ID: covidwho-1760077

ABSTRACT

BACKGROUND: Corona Virus Disease-19 (COVID-19), a current worldwide pandemic is a cuase of concern. Risk-adjusted differences in outcomes of the patients are not well characterized. Susceptibility to infection with respect to blood group, blood pressure, pulse rate, hemoglobin, age and BMI were analyzed. METHODS: Blood donors, of all the ages and gender, who recovered from COVID-19 infection, were selected for the study Samples from Regional laboratory and the Central blood bank of Hafr al Batin, Saudi Arabia were collected. Out of 1508 healthy blood donor 134 had recovered from corona without any preexisting diseases. RESULTS: Major donors were male (85.1%). 28% donors in age range of 26-35 years. O+(32.8%) were the highest donors. Systolic and diastolic blood pressure and pulse rate elevated significantly of age group 46-55 (p<0.05) and 56-65 (p<0.001). Systolic blood pressure in males (134.13 ± 9.57) was significantly higher (p<0.05) than those of females (129.35 ± 10.61). Donors with Rh+ significantly higher systolic (p<0.05) and pulse rate (p<0.05) as compared to Rh-. DISCUSSION: O+ donors were highly susceptible. Blood pressure, pulse rate and Hb alter with age. Males exhibit higher variation in systolic blood pressure, with Rh+ factor playing a predominant role. Donors above 45-years of age and a high BMI have significantly elevated blood pressure and pulse. These results are challenging or contradictory from the results of Turkish and Chinese studies where blood group A+ was more predominantly affected by the SARS-CoV-2 with minimum infection rate on females and Rh- donors. CONCLUSION: Factors like blood group V-2 treatment especially with the age group of 45 years and above.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330211

ABSTRACT

The novel Coronavirus, declared as a pandemic by WHO, has caused a health crisis and disrupted the daily course of the people globally. The effectiveness of Chest X-ray (CXR) in the differentiation of COVID from non-COVID has exhorted us to propose a diagnostic model based on deep features. This paper proposes a diagnostic framework to diagnose COVID-19 from Chest X-rays (CXR). Further Grad-CAM visualizations are shown to get a visual interpretation for the predicted images. We validated the performance of the proposed diagnostic model using the area under the curve (AUC), accuracy, precision, recall, F1-score and geometric mean (G-mean). Few popular machine learning models such as random forest, dense neural network, support vector machine (SVM), twin SVM (TWSVM), extreme learning machine (ELM), random vector functional link (RVFL) and kernel ridge regression (KRR) have been selected for diagnosing the COVID cases. The deep features are extracted by transfer learning. Grad-CAM visualizations are presented for the predicted images. We have achieved the best AUC score of 0.98 on TWSVM classifier on the feature vector extracted by ResNet50 architecture. The feature vector extracted from ResNet50 outperforms all other CNN architecture rank wise based on AUC. The experimental outcome indicates the efficiency of the proposed diagnostic framework.

3.
Curr Pharmacol Rep ; : 1-22, 2022 Mar 08.
Article in English | MEDLINE | ID: covidwho-1734089

ABSTRACT

The aim of the present study was to test the binding affinity of methylxanthines (caffeine/theine, methylxanthine, theobromine, theophylline and xanthine) to three potential target proteins namely Spike protein (6LZG), main protease (6LU7) and nucleocapsid protein N-terminal RNA binding domain (6M3M) of SARS-CoV-2. Proteins and ligand were generated using AutoDock 1.5.6 software. Binding affinity of methylxanthines with SARS-CoV-2 target proteins was determined using Autodock Vina. MD simulation of the best interacting complexes was performed using GROMACS 2018.3 (in duplicate) and Desmond program version 2.0 (academic version) (in triplicate) to study the stabile interaction of protein-ligand complexes. Among the selected methylxanthines, theophylline showed the best binding affinity with all the three targets of SARS-CoV-2 (6LZG - 5.7 kcal mol-1, 6LU7 - 6.5 kcal mol-1, 6M3M - 5.8 kcal mol-1). MD simulation results of 100 ns (in triplicate) showed that theophylline is stable in the binding pockets of all the selected SARS-CoV-2 proteins. Moreover, methylxanthines are safer and less toxic as shown by high LD50 value with Protox II software as compared to drug chloroquine. This research supports the use of methylxanthines as a SARS-CoV-2 inhibitor. It also lays the groundwork for future studies and could aid in the development of a treatment for SARS-CoV-2 and related viral infections. Supplementary Information: The online version contains supplementary material available at 10.1007/s40495-021-00276-3.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-320204

ABSTRACT

COVID-19 has been declared as global epidemic and currently there is no drug/vaccine available to treat COVID-19. All over the world, several studies are being conducted to discover the antiviral drugs against COVI-19. Traditional medicinal plants have long history to treat viral infections. We adopted in silico approach to find out if unique phytocompounds such as emodin ( Rheum emodi) , thymol and carvacrol ( Thymus serpyllum) and artemisnin ( Artemisia annua) could physically bind COVID-19 target proteins such as SARS-CoV-2 spike glycoprotein (PDB ID: 6VXX), SARS-CoV-2 spike ectodomain structure (PDB ID: 6VYB), and SARS coronavirus spike receptor-binding domain (PDB ID: 2AJF) and in turn preventCOVID-19 binding to the host receptor ACE2. Since Chloroquine (a standard antimalarial drug) has been looked as potential therapy against COVID-19, we also compared the binding of chloroquine and plant origin artemisnin antimalarial drug for its interaction with 6VXX, 6VY and 2AJF. Molecular docking studies using AutoDock/Vina software revealed that among all the phytocompounds artemisinin showed best binding affinity with 6VXX, 6VYB and 2AJF with E total -10.5 KJ mol -1 , -10.3 KJ mol -1 , and -9.1 KJ mol -1 respectively. Whereas emodin, carvacrol and thymol binds with 6VXX, 6VYB and 2AJF with E total -6.4, -6.8, -6.9 KJ mol -1 , -8.8, -6.8, -7.4 KJ mol -1 , and -6.9, -7.4, -7.2 respectively. Similarly, with Autodock/Vina chloroquine showed less binding affinity with 6VXX (-5.6 KJ mol -1 ), 6VYB (-5.9 KJ mol -1 ) and 2AJF (-6.4 KJ mol -1 ) as compared to all phytocompounds. Toxicity prediction showed non-toxicity and non-carcinogen by admetSAR and PROTOX‑II software.

5.
Otolaryngology Case Reports ; : 100400, 2022.
Article in English | ScienceDirect | ID: covidwho-1634322

ABSTRACT

Keratosis obturans is a rare entity which presents with pain, conductive hearing loss and very rarely facial nerve palsy due to pressure effects. HRCT temporal bone can help in differentiating keratosis obturans from canal cholesteatoma and can also show any pressure effects on facial canal. Prompt diagnosis and its differentiation from other similar conditions like canal cholesteatoma and impacted wax is warranted to avoid complications.

6.
Critical Care Medicine ; 50:98-98, 2022.
Article in English | Academic Search Complete | ID: covidwho-1596078

ABSTRACT

Our case is a pregnant patient who developed AMAN post COVID-19 infection. B Introduction: b COVID-19 disease has increasingly reported neurological complications. Our pregnant patient had AMAN post COVID-19, which led to premature delivery, and prolonged recovery. [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

7.
Sustainability ; 14(1):143, 2022.
Article in English | MDPI | ID: covidwho-1580486

ABSTRACT

Recently, it has become an important issue to ensure sustainability, especially in food supply chains, against the rapidly growing population, increasing demand, and sudden disruptions caused by uncertain times such as that caused by COVID-19. Since food supply chains has vulnerable products and processes, it is critical to understand the sustainability factors of food supply chains especially in uncertain times such during the COVID-19 pandemic. This study aims to determine sustainability factors of food supply chains. An Interpretive Structural Modelling method is used to state the relations between sustainability factors of food supply chains. As a result of the study, Information Sharing and Managerial Approaches are classified as driving factors;Food Safety and Security, Know-How Transfer, Logistics Networking, Risk Mitigation, Employee Commitment, Innovation, Traceability and Responsiveness are categorized as linkage factors. This article will be beneficial for managers in helping them develop sustainable food supply chains during uncertain times by focusing on traceability, information sharing, know-how transfer, food safety and security.

8.
Front Immunol ; 12: 741502, 2021.
Article in English | MEDLINE | ID: covidwho-1477825

ABSTRACT

Host innate immune response follows severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and it is the driver of the acute respiratory distress syndrome (ARDS) amongst other inflammatory end-organ morbidities. Such life-threatening coronavirus disease 2019 (COVID-19) is heralded by virus-induced activation of mononuclear phagocytes (MPs; monocytes, macrophages, and dendritic cells). MPs play substantial roles in aberrant immune secretory activities affecting profound systemic inflammation and end-organ malfunctions. All follow the presence of persistent viral components and virions without evidence of viral replication. To elucidate SARS-CoV-2-MP interactions we investigated transcriptomic and proteomic profiles of human monocyte-derived macrophages. While expression of the SARS-CoV-2 receptor, the angiotensin-converting enzyme 2, paralleled monocyte-macrophage differentiation, it failed to affect productive viral infection. In contrast, simple macrophage viral exposure led to robust pro-inflammatory cytokine and chemokine expression but attenuated type I interferon (IFN) activity. Both paralleled dysregulation of innate immune signaling pathways, specifically those linked to IFN. We conclude that the SARS-CoV-2-infected host mounts a robust innate immune response characterized by a pro-inflammatory storm heralding end-organ tissue damage.


Subject(s)
COVID-19/virology , Immunity, Innate , Macrophages/virology , SARS-CoV-2/pathogenicity , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/immunology , COVID-19/metabolism , Cells, Cultured , Cytokines/genetics , Cytokines/metabolism , Gene Expression Profiling , Gene Regulatory Networks , Host-Pathogen Interactions , Humans , Immunity, Innate/genetics , Inflammation Mediators/metabolism , Macrophages/immunology , Macrophages/metabolism , Proteome , Proteomics , Receptors, Virus/genetics , Receptors, Virus/metabolism , SARS-CoV-2/immunology , Signal Transduction , Transcriptome
9.
Business Process Management Journal ; 27(6):1775-1803, 2021.
Article in English | ProQuest Central | ID: covidwho-1462593

ABSTRACT

PurposeThis research investigates the impact of the strategic sourcing process on the supply chain response to COVID-19. The paper presents practitioners' perspectives (experts in supply chain management, especially involved in the procurement field) on the strategic sourcing process's impact on the supply chain response.Design/methodology/approachThe study follows a survey-based approach for data collection. It uses a descriptive survey methodology where questions related to the impact of the strategic sourcing process on the supply chain response in the face of the coronavirus pandemic were explored by practitioners.FindingsIn total, 130 valid responses were obtained. The results showed that the majority of respondents agreed or strongly agreed that strategic sourcing positively impacts the supply chain response amid the COVID-19 effects. Also, for the five phases of the strategic sourcing process, the majority of respondents considered them as a high and very high impact on the supply chain response.Research limitations/implicationsThis paper provides timely insights for practitioners and academics, especially those involved in the supply chain management area, showing how the strategic sourcing process plays an important role in making supply chains more responsive amid disruption situations.Practical implicationsFindings of this paper clearly shows the impact of the phases of the strategic sourcing process on the responsiveness of the supply chains amid the COVID-19 pandemic. This can encourage supply chain leadership to devote more time to strategic sourcing initiatives to generate improvements on the supply chain performance.Originality/valueThis paper is unique since it brings an unexplored relation in respect to strategic sourcing amid disruption situations, such as the COVID-19 pandemic, from a practitioner's perspective. It also significantly contributes to developing new directions for the supply chain management domain to deal with large-scale disruptions, such as the coronavirus pandemic.

10.
Am J Otolaryngol ; 43(1): 103220, 2022.
Article in English | MEDLINE | ID: covidwho-1401162

ABSTRACT

BACKGROUND: It is an incontrovertible fact that the Rhino Orbital Cerebral Mucormycosis (ROCM) upsurge is being seen in the context of COVID-19 in India. Briefly presented is evidence that in patients with uncontrolled diabetes, a dysfunctional immune system due to SARS-COV-2 and injudicious use of corticosteroids may be largely responsible for this malady. OBJECTIVE: To find the possible impact of COVID 19 infection and various co-morbidities on occurrence of ROCM and demonstrate the outcome based on medical and surgical interventions. METHODOLOGY: Prospective longitudinal study included patients diagnosed with acute invasive fungal rhinosinusitis after a recent COVID-19 infection. Diagnostic nasal endoscopy (DNE) was performed on each patient and swabs were taken and sent for fungal KOH staining and microscopy. Medical management included Injection Liposomal Amphotericin B, Posaconazole and Voriconazole. Surgical treatment was restricted to patients with RT PCR negative results for COVID-19. Endoscopic, open, and combined approaches were utilized to eradicate infection. Follow-up for survived patients was maintained regularly for the first postoperative month. RESULTS: Out of total 131 patients, 111 patients had prior history of SARS COVID 19 infection, confirmed with a positive RT-PCR report and the rest 20 patients had no such history. Steroids were received as a part of treatment in 67 patients infected with COVID 19. Among 131 patients, 124 recovered, 1 worsened and 6 died. Out of 101 known diabetics, 98 recovered and 3 had fatal outcomes. 7 patients with previous history of COVID infection did not have any evidence of Diabetes mellitus, steroid intake or any other comorbidity. CONCLUSION: It can be concluded that ROCM upsurge seen in the context of COVID-19 in India was mainly seen in patients with uncontrolled diabetes, a dysfunctional immune system due to SARS-COV-2 infection and injudicious use of corticosteroids.


Subject(s)
COVID-19/immunology , Mucormycosis/immunology , Adrenal Cortex Hormones/adverse effects , Antifungal Agents/therapeutic use , COVID-19/epidemiology , Diabetes Complications/immunology , Diagnostic Imaging , Endoscopy , Female , Humans , India/epidemiology , Longitudinal Studies , Male , Middle Aged , Mucormycosis/drug therapy , Mucormycosis/epidemiology , Pandemics , Prospective Studies , Risk Factors , SARS-CoV-2
11.
Curr Pharmacol Rep ; 7(4): 135-149, 2021.
Article in English | MEDLINE | ID: covidwho-1372831

ABSTRACT

COVID-19, the disease caused by SARS-CoV-2, has been declared as a global pandemic. Traditional medicinal plants have long history to treat viral infections. Our in silico approach suggested that unique phytocompounds such as emodin, thymol and carvacrol, and artemisinin could physically bind SARS-CoV-2 spike glycoproteins (6VXX and 6VYB), SARS-CoV-2 B.1.351 South Africa variant of Spike glycoprotein (7NXA), and even with ACE2 and prevent the SARS-CoV-2 binding to the host ACE2, TMPRSS2 and neutrapilin-1 receptors. Since Chloroquine has been looked as potential therapy against COVID-19, we also compared the binding of chloroquine and artemisinin for its interaction with spike proteins (6VXX, 6VYB) and its variant 7NXA, respectively. Molecular docking study of phytocompounds and SARS-CoV-2 spike protein was performed by using AutoDock/Vina software. Molecular dynamics (MD) simulation was performed for 50ns. Among all the phytocompounds, molecular docking studies revealed lowest binding energy of artemisinin with 6VXX and 6VYB, with Etotal -10.5 KJ mol-1 and -10.3 KJ mol-1 respectively. Emodin showed the best binding affinity with 6VYB with Etotal -8.8 KJ mol-1and SARS-CoV-2 B.1.351 variant (7NXA) with binding energy of -6.4KJ mol-1. Emodin showed best interactions with TMPRSS 2 and ACE2 with Etotal of -7.1 and -7.3 KJ mol-1 respectively, whereas artemisinin interacts with TMPRSS 2 and ACE2 with Etotal of -6.9 and -7.4 KJ mol-1 respectively. All the phytocompounds were non-toxic and non-carcinogenic. MD simulation showed that artemisinin has more stable interaction with 6VYB as compared to 6VXX, and hence proposed as potential phytochemical to prevent SARS-CoV-2 interaction with ACE-2 receptor. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40495-021-00259-4.

12.
J Biomol Struct Dyn ; 39(11): 4175-4184, 2021 07.
Article in English | MEDLINE | ID: covidwho-1343548

ABSTRACT

SARS coronavirus (COVID-19) is a real health challenge of the 21st century for scientists, health workers, politicians, and all humans that has severe cause epidemic worldwide. The virus exerts its pathogenic activity through by mechanism and gains the entry via spike proteins (S) and Angiotensin-Converting Enzyme 2 (ACE2) receptor proteins on host cells. The present work is an effort for a computational target to block the residual binding protein (RBP) on spike proteins (S), Angiotensin-Converting Enzyme 2 (ACE2) receptor proteins by probiotics namely Plantaricin BN, Plantaricin JLA-9, Plantaricin W, Plantaricin D along with RNA-dependent RNA polymerase (RdRp). Docking studies were designed in order to obtain the binding energies for Plantaricin metabolites. The binding energies for Plantaricin W were -14.64, -11.1 and -12.68 for polymerase, RBD and ACE2 respectively comparatively very high with other compounds. Plantaricin W, D, and JLA-9 were able to block the residues (THR556, ALA558) surrounding the deep grove catalytic site (VAL557) of RdRp making them more therapeutically active for COVID-19. Molecular dynamics studies further strengthen stability of the complexes of plantaricin w and SARS-CoV-2 RdRp enzyme, RBD of spike protein, and human ACE2 receptor. The present study present multi-way options either by blocking RBD on S proteins or interaction of S protein with ACE2 receptor proteins or inhibiting RdRp to counter any effect of COVID-19 by Plantaricin molecules paving a way that can be useful in the treatment of COVID-19 until some better option will be available.Communicated by Ramaswamy H. Sarma.


Subject(s)
COVID-19 , Probiotics , Antiviral Agents/pharmacology , Humans , Protein Binding , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism
13.
Research in Transportation Economics ; : 101114, 2021.
Article in English | ScienceDirect | ID: covidwho-1307165

ABSTRACT

The coronavirus (COVID-19) pandemic has severely affected the supply chain all over. A major challenge for the supply chain (SC) is to address this disruption risk and bring sustainability to SC. The objective of this paper is to identify the stakeholders' requirements and critical success factors (CSFs) for the sustainability initiative in SC during this pandemic situation. Three potential stakeholders' requirements and a total of 16 critical success factors have been identified by taking inputs from experts and decision-makers. Further, these critical factors are analyzed and ranked based on a hybrid quality function deployment (QFD)-best-worst methodology (BWM). The QFD method has been used to identify the stakeholder’ requirements. And, the BWM has been adopted to prioritize the CSFs. The scientific value of the study is the contribution of the framework model for the sustainable initiatives in the SC during the COVID-19 pandemic outbreak, identification of stakeholders’ requirements and CSFs, and prioritizes these CSFs. The top three most critical success factors are found to be social distancing, emergency logistics systems, and emergency backup facilities. The proposed framework provides a roadmap to operation and supply chain managers to come up with good solutions for sustainability initiatives in the supply chain during and after the pandemic outbreak.

14.
Biocatalysis and Agricultural Biotechnology ; : 102072, 2021.
Article in English | ScienceDirect | ID: covidwho-1283939

ABSTRACT

The current study was focused on the investigation of anticancer activity of Scindapsus Officinalis fruit extract embedded silver nanoparticles (So-AgNPs) followed by anticovid activity prognosis of major phytocompounds, which participate in nanoformulation synthesis. The synthesis process involved the addition of AgNO3 solution (1 mM) and color change of the extract from light brown to dark, confirmed the formation of silver nanoparticles. Further, the characterization of synthesized So-AgNPs were done using different spectroscopical and microscopical techniques. FTIR spectra of So-AgNPs indicated vibrational peaks of polyphenolic hydroxyl groups, which are responsible for the stabilization of nanoformulation. Others microscopy methods such as SEM, TEM, XRD, and EDX illustrated that the synthesized So-AgNPs consist irregular size, spherical shape and thoroughly dispersed above the plane. Anticancer evaluation illustrated that the So-AgNPs have dose dependent anti-breast and anti-hepatic cancer activity (range of 97.72 ± 0.42 – 54.86 ± 0.46 % cell viability), which were noticed more effective than raw fruit extract of Scindapsus Officinalis. The computational anticovid prediction of major phyto-compound of the extract [which designate as inhibitor 1: ((2R,3S,4S,5R)-2-(hydroxymethyl)-6-(((1S,5S)-1-methyl-5-(2-methylprop-1-en-1-yl)cyclopent-2-en-1-yl)oxy)tetrahydro-2H-pyran-3,4,5-triol)] illustrated moderate tendency to interact with corona main protease enzyme (expected pIC > 6 μM). However, the molecular docking and dynamics studies showed that selected compounds have moderate tendency to interact human dihydrofolate reductase and topoisomerase 1 enzyme. The accomplished approach shows that So-AgNPs with adsorbed phytocompounds on its surface consist valuable experimentally proved anticancer potency and computationally predicted anticovid effect. Thus, the formulation can be used as an alternative to the covid infected cancer population.

15.
Sustainability ; 13(12):6690, 2021.
Article in English | MDPI | ID: covidwho-1270110

ABSTRACT

The purpose of this study is to employ the existing theory on crisis management and corporate branding in a service context to explore how tourism businesses in Thailand can recover from the crisis caused by the impact of COVID-19. To manage the impact of COVID-19, the concepts of crisis management from different scholars are integrated, and crisis management is divided into three phases: the Pre-Crisis, Crisis, and Post-Crisis phases. This exploratory research employs stakeholder interviews to discover the impacts of COVID-19 on tourism businesses and attempts to develop guidelines for recovering tourism businesses within the service context. Our findings indicate that a strong brand and its proper management can help firms to survive during the crisis period. Moreover, our findings highlight the importance of communication for engaging with all staff during the recovery period. This paper sheds light on how a brand is employed as a proactive strategy to mitigate the impacts of the crisis. Most brands have been affected by the COVID-19 pandemic, and only strong brands are able to survive. Our study also adds to the limited empirical evidence on tourism business recovery during COVID-19 in the context of a developing country. From practitioners’ perspectives, trust, solid relationships, and honest communication with their business partners play an important role in survival after the crisis. Additionally, in this paper, corporate branding is conceived as a strategic tool that affects how staff and stakeholders can collaborate and unite in response to the crisis.

16.
Front Microbiol ; 12: 647295, 2021.
Article in English | MEDLINE | ID: covidwho-1221955

ABSTRACT

The rapid spread of COVID-19, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a worldwide health emergency. Unfortunately, to date, a very small number of remedies have been to be found effective against SARS-CoV-2 infection. Therefore, further research is required to achieve a lasting solution against this deadly disease. Repurposing available drugs and evaluating natural product inhibitors against target proteins of SARS-CoV-2 could be an effective approach to accelerate drug discovery and development. With this strategy in mind, we derived Marine Natural Products (MNP)-based drug-like small molecules and evaluated them against three major target proteins of the SARS-CoV-2 virus replication cycle. A drug-like database from MNP library was generated using Lipinski's rule of five and ADMET descriptors. A total of 2,033 compounds were obtained and were subsequently subjected to molecular docking with 3CLpro, PLpro, and RdRp. The docking analyses revealed that a total of 14 compounds displayed better docking scores than the reference compounds and have significant molecular interactions with the active site residues of SARS-CoV-2 virus targeted proteins. Furthermore, the stability of docking-derived complexes was analyzed using molecular dynamics simulations and binding free energy calculations. The analyses revealed two hit compounds against each targeted protein displaying stable behavior, binding affinity, and molecular interactions. Our investigation identified two hit compounds against each targeted proteins displaying stable behavior, higher binding affinity and key residual molecular interactions, with good in silico pharmacokinetic properties, therefore can be considered for further in vitro studies.

17.
Indian J Tuberc ; 67(4S): S69-S78, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1125264

ABSTRACT

Multiple drugs taken for long duration in tuberculosis (TB) treatment, especially drug resistant TB (DR-TB), may produce adverse drug reactions (ADRs). Although any anti-TB drug can cause ADRs, but these are more common with drugs used for treatment of DR-TB. However, most of ADRs with these drugs are mild or moderate and can be managed if adequate supervision and monitoring is done. However, few ADRs can be severe or potentially life-threatening and may require removal of the offending drug(s). TB patients having comorbidities and on treatment for them may experience drug interaction with anti TB drugs and may require dose modification or change of drug. For a good TB treatment outcome patient's compliance should be ensured, and adverse events and drug interactions should be appropriately addressed by the clinicians. This article outlines the majority of the possible ADRs to anti-TB drugs used for management of DR-TB and their common drug interactions with practical recommendations to identify the possible drug(s) responsible and the most adequate management in each situation.


Subject(s)
Antitubercular Agents/adverse effects , Tuberculosis, Multidrug-Resistant/drug therapy , Drug Interactions , Drug-Related Side Effects and Adverse Reactions , Humans
18.
J Pharm Sci ; 110(6): 2346-2354, 2021 06.
Article in English | MEDLINE | ID: covidwho-1121342

ABSTRACT

The novel coronavirus (SARS-CoV-2) outbreak has started taking away the millions of lives worldwide. Identification of known and approved drugs against novel coronavirus disease (COVID-19) seems to be an urgent need for the repurposing of the existing drugs. So, here we examined a safe strategy of using approved drugs of SuperDRUG2 database against modeled membrane protein (M-protein) of SARS-CoV-2 which is essential for virus assembly by using molecular docking-based virtual screening. A total of 3639 drugs from SuperDRUG2 database and additionally 14 potential drugs reported against COVID-19 proteins were selected. Molecular docking analyses revealed that nine drugs can bind the active site of M-protein with desirable molecular interactions. We therefore applied molecular dynamics simulations and binding free energy calculation using MM-PBSA to analyze the stability of the compounds. The complexes of M-protein with the selected drugs were simulated for 50 ns and ranked according to their binding free energies. The binding mode of the drugs with M-protein was analyzed and it was observed that Colchicine, Remdesivir, Bafilomycin A1 from COVID-19 suggested drugs and Temozolomide from SuperDRUG2 database displayed desirable molecular interactions and higher binding affinity towards M-protein. Interestingly, Colchicine was found as the top most binder among tested drugs against M-protein. We therefore additionally identified four Colchicine derivatives which can bind efficiently with M-protein and have better pharmacokinetic properties. We recommend that these drugs can be tested further through in vitro studies against SARS-CoV-2 M-protein.


Subject(s)
COVID-19 , Pharmaceutical Preparations , Antiviral Agents/pharmacology , Drug Repositioning , Humans , Membrane Proteins , Molecular Docking Simulation , Molecular Dynamics Simulation , SARS-CoV-2
19.
Curr Pharm Des ; 27(9): 1202-1210, 2021.
Article in English | MEDLINE | ID: covidwho-1069678

ABSTRACT

BACKGROUND: The spike (S) glycoprotein of SARS corona virus (SARS-CoV-2) and human Angiotensin- converting enzyme 2 (ACE2), are both considered the key factors for the initiation of virus infection. The present work is an effort for computational target to block the spike proteins (S) and ACE2 receptor proteins with Macrolide antibiotics like Azithromycin, (AZM), Clarithromycin (CLAM) and Erythromycin (ERY) along with RNA-dependent RNA polymerase (RdRp). METHODS: Three-dimensional structure of the SARS-CoV-2RdRp was built by the SWISS-MODEL server, the generated structure showed 96.35% identity to the available structure of SARS-Coronavirus NSP12 (6NUR), for model validity, we utilized the SWISS-model server quality parameters and Ramachandran plots. RESULTS: These compounds were able to block the residues (Arg553, Arg555, and Ala558) surrounding the deep grove catalytic site (Val557) of RdRp and thus plays an important role in tight blocking of enzyme active site. Reference drug Remdesivir was used to compare the docking score of antibiotics with RdRp. Docking value exhibited good binding energy (-7.7 up to -8.2 kcal/mol) with RdRp, indicating their potential as a potent RdRp inhibitor. Interaction of CLAM and ERY presented low binding energy (-6.8 and -6.6) with the ACE2 receptor. At the same time, CLAM exhibited a good binding affinity of -6.4 kcal/mol, making it an excellent tool to block the attachment of spike protein to ACE2 receptors. Macrolides not only affected the attachment to ACE2 but also blocked the spike proteins further, consequently inhibiting the internalization in the host cell. Three Alkyl bonds between Arg555, Ala558, and Met542 by CLAM and two Alkyl bonds of Arg624 and Lys621 by ERY plays an important role for RdRp inactivation, that can prevent the rise of newly budded progeny virus. These macrolides interacted with the main protease protein in the pocket responsible for the dimerization and catalytic function of this protein. The interaction occurred with residue Glu166, along with the catalytic residues (Tyr343, and His235) of Endoribonuclease (NSP15) protein. CONCLUSION: The present study gives three-way options either by blocking S proteins or ACE2 receptor proteins or inhibiting RdRp to counter any effect of COVID-19 by macrolide and could be useful in the treatment of COVID-19 till some better option available.


Subject(s)
COVID-19 , Anti-Bacterial Agents/pharmacology , Antiviral Agents , Humans , Macrolides/pharmacology , Protein Binding , SARS-CoV-2
20.
Biomed Pharmacother ; 137: 111356, 2021 May.
Article in English | MEDLINE | ID: covidwho-1062250

ABSTRACT

All the plants and their secondary metabolites used in the present study were obtained from Ayurveda, with historical roots in the Indian subcontinent. The selected secondary metabolites have been experimentally validated and reported as potent antiviral agents against genetically-close human viruses. The plants have also been used as a folk medicine to treat cold, cough, asthma, bronchitis, and severe acute respiratory syndrome in India and across the globe since time immemorial. The present study aimed to assess the repurposing possibility of potent antiviral compounds with SARS-CoV-2 target proteins and also with host-specific receptor and activator protease that facilitates the viral entry into the host body. Molecular docking (MDc) was performed to study molecular affinities of antiviral compounds with aforesaid target proteins. The top-scoring conformations identified through docking analysis were further validated by 100 ns molecular dynamic (MD) simulation run. The stability of the conformation was studied in detail by investigating the binding free energy using MM-PBSA method. Finally, the binding affinities of all the compounds were also compared with a reference ligand, remdesivir, against the target protein RdRp. Additionally, pharmacophore features, 3D structure alignment of potent compounds and Bayesian machine learning model were also used to support the MDc and MD simulation. Overall, the study emphasized that curcumin possesses a strong binding ability with host-specific receptors, furin and ACE2. In contrast, gingerol has shown strong interactions with spike protein, and RdRp and quercetin with main protease (Mpro) of SARS-CoV-2. In fact, all these target proteins play an essential role in mediating viral replication, and therefore, compounds targeting aforesaid target proteins are expected to block the viral replication and transcription. Overall, gingerol, curcumin and quercetin own multitarget binding ability that can be used alone or in combination to enhance therapeutic efficacy against COVID-19. The obtained results encourage further in vitro and in vivo investigations and also support the traditional use of antiviral plants preventively.


Subject(s)
COVID-19 , Catechols/pharmacology , Curcumin/pharmacology , Fatty Alcohols/pharmacology , Medicine, Ayurvedic/methods , Quercetin/pharmacology , SARS-CoV-2 , Antiviral Agents/pharmacology , COVID-19/drug therapy , Drug Repositioning/methods , Humans , Molecular Docking Simulation , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Viral Proteins/antagonists & inhibitors
SELECTION OF CITATIONS
SEARCH DETAIL