Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 19 de 19
Filter
1.
Applied nanoscience ; : 1-14, 2022.
Article in English | EuropePMC | ID: covidwho-1876720

ABSTRACT

The diagnosis of novel coronavirus (COVID-19) has gained the spotlight of the world’s scientific community since December 2019 and it remains an important issue due to the emergence of novel variants around the globe. Early diagnosis of coronavirus is captious to prevent and hard to control. This pandemic can be eradicated by implementing suppressing strategies which can lead to better outcomes and more lives being saved. Therefore, the analysis showed that COVID-19 can only be managed by adopting public health measures, such as testing, isolation and social distancing. Much work has been done to diagnose coronavirus. Various testing technologies have been developed, opted and modified for rapid and accurate detection. The advanced molecular diagnosis relies on the detection of SARS-CoV-2 as it has been considered the main causative agent of this pandemic. Studies have shown that several molecular tests are considered essential for the confirmation of coronavirus infection. Various serology-based tests are also used in the detection and diagnosis of coronavirus including point-of-care assays and high-throughput enzyme immunoassays that aid in the diagnosis of COVID-19. Both these assays are time-consuming and have less diagnostic accuracy. Nanotechnology has the potential to develop new strategies to combat COVID-19 by developing diagnostics and therapeutics. In this review, we have focused on the nanotechnology-based detection techniques including nanoparticles and biosensors to obstruct the spread of SARS-CoV-2.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-321129

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), is a novel beta coronavirus emerged in China in 2019. Coronavirus uses spike glycoprotein to interact with host angiotensin-converting enzyme 2 (ACE2) and ensure cell recognition. High infectivity of SARS-CoV-2 raises questions on spike-ACE2 binding affinity and its neutralization by anti-SARS-CoV monoclonal antibodies (mAbs). Here, we observed Val-to-Lys417 mutation in the receptor-binding domains (RBD) of SARS-CoV-2, which established a Lys-Asp electrostatic interaction enhancing its ACE2-binding. Pro-to-Ala475 substitution and Gly482 insertion in the A GSTPCN G V-loop of RBD hindered neutralization of SARS-CoV-2 by anti-SARS-CoV mAbs. In addition, we identified unique and structurally conserved conformational-epitopes on RBDs, which can be potential therapeutic targets. Collectively, we provide new insights into the mechanisms underlying the high infectivity of SARS-CoV-2 and development of new effective neutralizing agents.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-304956

ABSTRACT

After the pandemic of SARS-CoV-2, it has influenced the health care practices around the world. Initial investigations indicate that patients with comorbidities are more fragile to this SARS-CoV-2 infection. They suggested postponing the routine treatment of cancer patients. However, few meta-analyses suggested evidences are not sufficient to hold the claim of the frailty of cancer patients to COVID-19, and they are not in favour of shelving the scheduled procedures. There are recent studies in which medical professionals, according to their competence, are referring to change the routine practices on how to manage the applicable therapeutic resources judiciously to combat this vital infection. This is a different study that reveals the cancer patients' viewpoint about how health care practices have been changed in their opinion during this pandemic year? Are they satisfied with their treatment or not? To serve the purpose, we gathered more than 60000 relevant tweets from Twitter to analyse the sentiment of cancer patients around the world. Our findings demonstrate that there is a surge in argument about cancer and its treatment after the outbreak of COVID-19. Most of the tweets are reasonable (52.6%) compared to the negative ones (24.3). We developed polarity and subjectivity distribution to better recognise the positivity/negativity in the sentiment. Results reveal that the polarity range of positive tweets is within the range of 0 to 0.5. Which means the tendency in the tweets is not so much positive but surely not negative. It is a piece of modest statistical evidence in support of how natural language processing (NLP) can be accepted to better understand the patient's behaviour in real-time, and it may facilitate the medical professional to make better decision to organise the routine management of cancer patients.

4.
Phytomedicine Plus ; : 100226, 2022.
Article in English | ScienceDirect | ID: covidwho-1655020

ABSTRACT

Background : A. europaeum is a well mentioned Unani herb, belonging to Aristolochiaceae family and indigenous to the Eastern and Southern Europe. A. europaeum has traditionally been utilised in Unani medicine to treat respiratory ailments, gastrointestinal disorders, neurological disorders, hepatic disorders, genitourinary disorders, snake poisoning, vector-borne infections, and epidemic prophylaxis. This review aims to the compile previous and present available information concerning about the ethno-botanical aspects, phyto-chemical constituents, isolated metabolites, and pharmacological profiling of this herb correlating the principles of Unani doctrine, thereby may offer series of valuable data for researchers and pharmaceuticals to develop novel therapeutic ways. ‏ Material and methods : A detailed literature review has been conducted on A. europaeum in various electronic databases, including Pub Med, Web of Science, Wiley, Science Direct, Elsevier, Google Scholar, ACS publications, Springer Link etc. Furthermore, books (Unani ancient classical books) were consulted in Urdu, Arabic, Persian and English to collate the particulars. Results : The present literature survey incorrigibly illustrated the usage of A. europaeum as a prophylactic drug in several diseases such as chicken pox, plague, and viral fevers, including COVID-19 and therapeutically, aid in managing bronchitis, epilepsy, hepatitis, ascites, amenorrhea, paralysis, sciatica, lumbago, and urolithiasis. It has been well documented its usage in the form of powder, decoction, syrup, extract, and oil as a single drug or in compound formulations with the amalgamation of other herbs. Phyto-chemical analysis from various sections of the plant revealed the presence of varied chemical constituents for example essential oils (with four chemotypes), flavonoids, phenolic compounds, organic acids, vitamins, terpenes and sesquiterpenes. It has also been evaluated through in vitro, in vivo, in silico, preclinical and clinical trial models for diverse pharmacological activities such as antibacterial, anti-diabetic, and anti-proliferative activities, etc. Still, only sporadic herb studies have been published so far. Conclusion : The current paper highlights botany, ethno pharmacology, phyto-chemistry, pharmacology, and toxicology in depth. Preliminary pharmacological studies on different extracts and fractions of A. europaeum support the claim of Unani scholars that it is useful in the treatment of various diseases. However, immediate efforts must be made to determine its mechanism of action, efficacy, dosage, and safety in combating various pathological states. The study will undoubtedly serve as the basis for future research to further demonstrate the ethno medicinal and therapeutic potential for health-care product improvement.

5.
Clin Med Res ; 19(4): 179-182, 2021 12.
Article in English | MEDLINE | ID: covidwho-1581437

ABSTRACT

Objective: To assess the effect of chloroquine and hydroxychloroquine on cytokine release syndrome (CRS) in adult patients with coronavirus disease 2019 (COVID-19) having mild to moderate symptoms.Methods: This blinded, placebo-controlled, randomized study was conducted in the Department of Medicine, Pak Emirates Military Hospital Rawalpindi, from June 1-15, 2020. A total of 150 hospitalized patients were enrolled after diagnoses with COVID-19 through reverse transcription polymerase chain reaction (RT-PCR). They were divided into three groups: hydroxychloroquine plus general care (HGC, n=50), chloroquine plus general care (CGC, n=50); and only general care (OGC, n=50). The HGC group received treatment with hydroxychloroquine 400 mg every 12 hours for day one and 200 mg for the next 4 days. The CGC group received treatment with chloroquine 250 mg every 12 hours for 7 days. The OGC group was kept as a control with only general care. After 12 days, the patients were screened for development of CRS through detection of interleukin 6 (IL-6) in serum samples by using Roche cobas e411 electrochemiluminescence immunoassay analyzer.Results: The mean duration from onset of symptoms to randomization was 7.65 days (SD = 3.287 days; range, 2-15 days). The mean age of patients was 37.57 (range 19-63) years. Results showed that out of a total 150 patients, only 10 patients (6%, mean=1.93; CI=1.89-1.97, P=0.651) developed CRS in all study groups. Four patients (8%) developed CRS in the HGC group, 2 patients (4%) in the CGC group, and 4 patients (8%) in the OGC group. There was no significant difference in the mean level of CRS among study groups.Conclusion: Administration of hydroxychloroquine and chloroquine has no effect in reducing the development of CRS in patients with COVID-19 having mild to moderate symptoms.


Subject(s)
COVID-19 , Hydroxychloroquine , Adult , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Chloroquine/therapeutic use , Cytokine Release Syndrome , Humans , Hydroxychloroquine/therapeutic use , Middle Aged , SARS-CoV-2 , Treatment Outcome , Young Adult
6.
Cureus ; 13(11): e20031, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1560995

ABSTRACT

Introduction There are conflicting studies regarding the efficacy of tocilizumab use in coronavirus disease 2019 (COVID-19) disease. There is a special need to identify the parameters that could predict its response in early COVID-19 disease. Objective To report our experience with tocilizumab and correlate the magnitude of fall in c-reactive protein (CRP) as a predictor of its response to treatment in early COVID-19 disease. Methods All confirmed COVID-19 cases admitted to a tertiary healthcare hospital in Peshawar Pakistan, receiving ≥1 dose of intravenous tocilizumab, between March and September 2020 were included. Relevant clinical data of the patients were recorded and further divided into two categories based on the relative fall in CRP levels, 48 hours after tocilizumab administration. Adequate response (≥50% fall from baseline CRP), primary outcomes (fall in oxygen requirement and inflammatory biomarkers), and secondary outcome (all-cause mortality at day 28) were recorded. All outcomes were compared based on falls in CRP levels. Results A total of 27 patients were included. Males were 24 (88.8%) while females were three (11.1%). The mean age was 60.9±11.6 years. The mean day of illness at the time of tocilizumab administration was 4.26±3 days. After 48 hours of tocilizumab administration, 17 (62.9%) patients showed clinical improvement, with the mean SaO2/FiO2 ratio prior to treatment significantly increased (p<0.01). A significant reduction in CRP and ferritin levels was seen post-treatment (p <0.01 and p<0.01, respectively). Twenty (74.1%) patients demonstrated adequate response to tocilizumab while seven (25.9%) showed an inadequate response. Patients with adequate response had higher chances of improvement in oxygenation and lower in-hospital mortality (p-value 0.009 and 0.020, respectively). Conclusions Tocilizumab shows clinical improvement in a vast majority of patients. Being an early and sensitive predictor, a fall of ≥50% in CRP at 48 hours can be used to predict the overall response to tocilizumab as a guide to treatment.

7.
Cureus ; 13(10): e18973, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1504428

ABSTRACT

Introduction The clinicopathological description of dermatological manifestations of COVID-19 leaves much to be desired. There is a need to determine their association with disease severity, outcome, and other clinical variables. Objectives The objectives of this study are to record and histopathologically examine the cutaneous manifestations of COVID-19 and correlate these to age, disease severity, and mortality. Methods All confirmed COVID-19 patients admitted to a single tertiary healthcare hospital in Rawalpindi, Pakistan, were included. Their diseases were classified as mild, moderate, severe, and critical. The recent onset skin eruptions in these patients were recorded via photographs along with relevant clinical data. The photographs were independently reviewed by a group of three dermatologists without knowledge of the clinical information. The skin manifestations were divided into disease-specific and nonspecific categories using an already defined algorithm. Histopathological examination of skin manifestations was conducted. Results A total of 23% (n=47) had "new" skin manifestations. Specific skin findings were seen in 21.6% (n=44), which consisted of ecchymosis/purpura in 50% (n=22), maculopapular exanthem in 18% (n=8), livedo reticularis in 16.2% (n=7), ischemia/gangrene in 16.2% (n=7), perniosis in 15.9 % (n=7), vesiculo-bullous rash in 9% (n=4) and urticaria in 4% (n=1). Non-specific findings were seen in 6% (n=13) and included bedsores, dermatitis passivata, dryness, herpes labialis, oral ulcerations, and nasogastric tube-induced ulcerations. There was a significant association (p=0.03) between disease severity and specific skin lesions. Ischemia/gangrene was significantly associated with COVID-19 disease severity and mortality. Vesiculobullous lesions were associated with higher mortality, though not with disease severity. Livedo reticularis had a higher-than-expected count in critical disease, albeit statistically insignificant. The association of maculopapular exanthem and ecchymosis/purpura with severe/critical disease was statistically insignificant. Urticaria was significantly associated with low disease severity. Mean age with specific manifestations was 56.86 ± 15.81 and with nonspecific/without any manifestations was 42.58 ± 16.96, a highly significant difference, with p-value < 0.001. Old age (>60 years) was significantly associated with ecchymosis (p=0.038), maculopapular exanthem (p=0.021), and vesiculo-bullous rash (p=0.029). Histopathology varied according to the type of skin lesion. Conclusions Dermatological manifestations coexist in many patients and tend to appear more in severe cases of COVID-19 among the older age group and only minimally in mild/moderate cases. Their presence could help set prognostic criteria of COVID-19 disease in the future.

8.
Cureus ; 13(9): e17693, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1438873

ABSTRACT

BACKGROUND: The role of various corticosteroids in the management of COVID-19 is evolving. Following an initial lack of evidence, the relatively novel data, supporting the survival benefit to severe and critical COVID-19 patients, is of limited scale. MATERIALS AND METHODS: This retrospective study observed medical records and disease outcomes of 200 patients with moderate, severe and critical COVID-19 receiving methylprednisolone (MP). The dose of methylprednisolone was 0.5 to 2 mg per kg in these patients. RESULTS: Median age of presentation was 59 years. The median duration of symptoms at presentation was five days. The most common presenting symptoms were cough (77.5%), fever (67.5%) and shortness of breath (63.5%). Majority of patients (85%) presented in the first week of illness. One or more comorbidities were present in 75% of patients. Complications seen in the study cohort were cytokine release syndrome (CRS) 92 (46%), acute respiratory distress syndrome (ARDS) 44 (22%) and multi-organ dysfunction 17 (8.5%). The median time for initiation of corticosteroid therapy was four hours. Overall survival (OS) in patients receiving methylprednisolone was 83.5%. The OS for patients with moderate, severe and critical diseases was 97.8%, 86.2% and 62%, respectively (p<0.001). CONCLUSION: Steroids like methylprednisolone are useful in COVID-19 admitted patients and provide excellent survival outcomes.

9.
Pakistan Journal of Public Health ; 11(1):6-10, 2021.
Article in English | CAB Abstracts | ID: covidwho-1395735

ABSTRACT

The health care professionals (HCPs) in Pakistan are vulnerable to the negative psychological impact of the current COVID - 19 pandemic. The shortage of trained HCPs in Pakistan coupled with vulnerable infrastructure and depleted resources make the situation a source of psychological reactions like fear, anger, anxiety, and depression for HCPs during COVID - 19 outbreak. These psychological reactions are produced by the preceding thoughts and emotions according to the cognitive behavioral model. Therefore, a cognitive behavioral crisis intervention model (CBCIM) is proposed with aim of helping HCPs deal with these psychological reactions efficiently. The common components of CBCIM include the cognitive restructuring of the negative thoughts, teaching of relaxation and mindfulness exercises, the teaching of ACT - ADD approach and use of coping cards, district wise team - based act ion plan and the provision of these services to HCPs regularly even after the end of COVID - 19 pandemic.

10.
Int J Mol Sci ; 22(17)2021 Aug 24.
Article in English | MEDLINE | ID: covidwho-1374423

ABSTRACT

The novel coronavirus disease, caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), rapidly spreading around the world, poses a major threat to the global public health. Herein, we demonstrated the binding mechanism of PF-07321332, α-ketoamide, lopinavir, and ritonavir to the coronavirus 3-chymotrypsin-like-protease (3CLpro) by means of docking and molecular dynamic (MD) simulations. The analysis of MD trajectories of 3CLpro with PF-07321332, α-ketoamide, lopinavir, and ritonavir revealed that 3CLpro-PF-07321332 and 3CLpro-α-ketoamide complexes remained stable compared with 3CLpro-ritonavir and 3CLpro-lopinavir. Investigating the dynamic behavior of ligand-protein interaction, ligands PF-07321332 and α-ketoamide showed stronger bonding via making interactions with catalytic dyad residues His41-Cys145 of 3CLpro. Lopinavir and ritonavir were unable to disrupt the catalytic dyad, as illustrated by increased bond length during the MD simulation. To decipher the ligand binding mode and affinity, ligand interactions with SARS-CoV-2 proteases and binding energy were calculated. The binding energy of the bespoke antiviral PF-07321332 clinical candidate was two times higher than that of α-ketoamide and three times than that of lopinavir and ritonavir. Our study elucidated in detail the binding mechanism of the potent PF-07321332 to 3CLpro along with the low potency of lopinavir and ritonavir due to weak binding affinity demonstrated by the binding energy data. This study will be helpful for the development and optimization of more specific compounds to combat coronavirus disease.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus Protease Inhibitors/pharmacology , Lactams/pharmacology , Leucine/pharmacology , Nitriles/pharmacology , Proline/pharmacology , Antiviral Agents/therapeutic use , Catalytic Domain/drug effects , Coronavirus 3C Proteases/metabolism , Coronavirus Protease Inhibitors/therapeutic use , Humans , Lactams/therapeutic use , Leucine/therapeutic use , Lopinavir/pharmacology , Molecular Docking Simulation , Molecular Dynamics Simulation , Nitriles/therapeutic use , Proline/therapeutic use , Ritonavir/pharmacology , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology
11.
J Biomol Struct Dyn ; : 1-53, 2021 Jul 09.
Article in English | MEDLINE | ID: covidwho-1303835

ABSTRACT

There is currently a dearth of specific therapies to treat respiratory infections caused by the three related species of coronaviruses viz. SARS-CoV-2, SARS-CoV and MERS-CoV. Prevention from disease is currently the safest and most convenient alternative available. The present study aimed to evaluate the preventive and therapeutic effect of fifteen phytoconstituents from medicinal plants of Ayurveda against coronaviruses by in silico screening. All the phytoconstituents exhibited rapid GI absorption and bioavailability and most of them had no toxicity versus reference drug chloroquine. BAS analyses revealed that most of the phytocomponents had favorable bioactivity scores towards biological target proteins. Principal component analysis revealed that most of the phytoconstituents fell close to chloroquine in 3D projection of chemical space. Affinity of phytoconstituents towards SARS-CoV-2 spike protein-human ACE2 complex decreased as isomeldenin > tinosporaside > EGCG whereas in case of unbound ACE2, the strength of binding followed the order isomeldenin > tinosporaside > ellagic acid. Towards SARS-CoV-2 main and papain-like proteases, the affinity decreased as isomeldenin > EGCG > tinosporaside and EGCG > tinosporaside > isomeldenin, respectively. Most phytoconstituents displayed significant binding kinetics to the selected protein targets than chloroquine. SAR analysis revealed that isomeldenin, tinosporaside, EGCG and ellagic acid bind to viral spike glycoproteins via H-bond, Pi-Pi, Pi-sigma and Pi-alkyl type interactions. Molecular dynamics simulation of isomeldenin and EGCG with SARS-CoV and SARS-CoV-2 spike glycoproteins exhibited low deviations throughout the 100 ns simulation indicating good stability and compactness of the protein-ligand complexes. Thus, the above four phytoconstituents have the potential to emerge as prophylactic and therapeutic agents against coronaviruses if investigated further in vitro and in vivo. Communicated by Ramaswamy H. Sarma.

12.
Symmetry ; 13(6):1091, 2021.
Article in English | MDPI | ID: covidwho-1273515

ABSTRACT

As the COVID-19 pandemic rapidly spreads across the world, regrettably, misinformation and fake news related to COVID-19 have also spread remarkably. Such misinformation has confused people. To be able to detect such COVID-19 misinformation, an effective detection method should be applied to obtain more accurate information. This will help people and researchers easily differentiate between true and fake news. The objective of this research was to introduce an enhanced evolutionary detection approach to obtain better results compared with the previous approaches. The proposed approach aimed to reduce the number of symmetrical features and obtain a high accuracy after implementing three wrapper feature selections for evolutionary classifications using particle swarm optimization (PSO), the genetic algorithm (GA), and the salp swarm algorithm (SSA). The experiments were conducted on one of the popular datasets called the Koirala dataset. Based on the obtained prediction results, the proposed model revealed an optimistic and superior predictability performance with a high accuracy (75.4%) and reduced the number of features to 303. In addition, by comparison with other state-of-the-art classifiers, our results showed that the proposed detection method with the genetic algorithm model outperformed other classifiers in the accuracy.

13.
Mamm Genome ; 32(5): 389-400, 2021 10.
Article in English | MEDLINE | ID: covidwho-1258196

ABSTRACT

Acute Kidney Injury (AKI) is a common manifestation of COVID-19 and several cases have been reported in the setting of the high-risk APOL1 genotype (common genetic variants). This increases the likelihood that African American people with the high-risk genotype APOL1 are at increased risk for kidney disease in the COVID-19 environment. Single-nucleotide polymorphisms (SNPs) are found in various microRNAs (miRNAs) and target genes change the miRNA activity that leads to different diseases. Evidence has shown that SNPs increase/decrease the effectiveness of the interaction between miRNAs and disease-related target genes. The aim of this study is not only to identify miRSNPs on the APOL1 gene and SNPs in miRNA genes targeting 3'UTR but also to evaluate the effect of these gene variations in kidney patients and their association with SARS-COV-2 infection. In 3'UTR of the APOL1 gene, we detected 96 miRNA binding sites and 35 different SNPs with 10 different online software in the binding sites of the miRNA (in silico). Also we studied gene expression of patients and control samples by using qRT-PCR (in vitro). In silico study, the binding site of miR-6741-3p on APOL1 has two SNPs (rs1288875001, G > C; rs1452517383, A > C) on APOL1 3'UTR, and its genomic sequence is the same nucleotide as rs1288875001. Similarly, two other SNPs (rs1142591, T > A; rs376326225, G > A) were identified in the binding sites of miR-6741-3p at the first position. Here, the miRSNP (rs1288875001) in APOL1 3'UTR and SNP (rs376326225) in the miR-6741-3p genomic sequence are cross-matched in the same binding region. In vitro study, the relative expression levels were calculated by the 2-ΔΔCt method & Mann-Whitney U test. The expression of APOL1 gene was different in chronic kidney patients along with COVID-19. By these results, APOL1 expression was found lower in patients than healthy (p < 0.05) in kidney patients along with COVID-19. In addition, miR-6741-3p targets many APOL1-related genes (TLR7, SLC6A19, IL-6,10,18, chemokine (C-C motif) ligand 5, SWT1, NFYB, BRF1, HES2, NFYB, MED12L, MAFG, GTF2H5, TRAF3, angiotensin II receptor-associated protein, PRSS23) by evaluating online software in the binding sites of the miR-6741-3p. miR-6741-3p has not previously shown any association with kidney diseases and SARS-COV-2 infection. It assures that APOL1 can have a significant consequence in kidney-associated diseases by different pathways. Henceforth, this study represents and demonstrates an effective association between miR-6741-3p and kidney diseases, i.e., collapsing glomerulopathy, chronic kidney disease (CKD), acute kidney injury (AKI), and tubulointerstitial lesions susceptibility to SARS-COV-2 infection via in silico and in vitro exploration and recommended to have better insight.


Subject(s)
3' Untranslated Regions/genetics , Apolipoprotein L1/genetics , COVID-19/genetics , Kidney Diseases/genetics , MicroRNAs/genetics , Polymorphism, Single Nucleotide/genetics , Binding Sites/genetics , Case-Control Studies , Genotype , Humans , Kidney/pathology , SARS-CoV-2/pathogenicity
14.
Oxf Med Case Reports ; 2021(4): omab024, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1219706

ABSTRACT

Lymphoma of bone is a rare neoplasm composed of malignant lymphoid cells, producing a tumefactive lesion within bone. We report a 13-year-old male who presented with progressively increasing swellings at the right shoulder and right mid-thigh for one month. Radiological images revealed lytic destructive lesions associated with soft tissue masses in both sites and a pathological fracture on the right humerus. The patient had no significant medical history. Histological, immunohistochemical and fluorescent in-situ hybridization assessment of biopsies from the lesions confirmed the diagnosis of primary non-Hodgkin lymphoma of bone. Unfortunately, due to coronavirus disease 2019 outbreak, the patient was unable to follow-up treatment and died shortly after establishment of the diagnosis. Delay in diagnosis and treatment is of serious concern when it comes to improve the prognosis of patients with this disease.

15.
J Biomol Struct Dyn ; : 1-32, 2021 Feb 01.
Article in English | MEDLINE | ID: covidwho-1066089

ABSTRACT

A sudden outbreak of a novel coronavirus SARS-CoV-2 in 2019 has now emerged as a pandemic threatening to efface the existence of mankind. In absence of any valid and appropriate vaccines to combat this newly evolved agent, there is need of novel resource molecules for treatment and prophylaxis. To this effect, flavonol morin which is found in fruits, vegetables and various medicinal herbs has been evaluated for its antiviral potential in the present study. PASS analysis of morin versus reference antiviral drugs baricitinib, remdesivir and hydroxychloroquine revealed that morin displayed no violations of Lipinski's rule of five and other druglikeness filters. Morin also displayed no tumorigenic, reproductive or irritant effects and exhibited good absorption and permeation through GI (clogP <5). In principal component analysis, morin appeared closest to baricitinib in 3D space. Morin displayed potent binding to spike glycoprotein, main protease 3CLPro and papain-like protease PLPro of SARS-CoV-2, SARS-CoV and MERS-CoV using molecular docking and significant binding to three viral-specific host proteins viz. human ACE2, importin-α and poly (ADP-ribose) polymerase (PARP)-1, further lending support to its antiviral efficacy. Additionally, morin displayed potent binding to pro-inflammatory cytokines IL-6, 8 and 10 also supporting its anti-inflammatory activity. MD simulation of morin with SARS-CoV-2 3CLPro and PLPro displayed strong stability at 300 K. Both complexes exhibited constant RMSDs of protein side chains and Cα atoms throughout the simulation run time. In conclusion, morin might hold considerable therapeutic potential for the treatment and management of not only COVID-19, but also SARS and MERS if studied further. Communicated by Ramaswamy H. Sarma.

16.
J Biomol Struct Dyn ; : 1-21, 2020 Dec 08.
Article in English | MEDLINE | ID: covidwho-963313

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel etiological agent of coronavirus disease 2019 (COVID-19). Nigella sativa, commonly known as black seed or black cumin, has been a historical and traditional plant since thousands of years. Based on their therapeutic efficacy, the chief components of terpenoids and flavonoids were selected from N. sativa seeds and seed oil. This study was designed to check the antiviral efficacy of N. sativa main phytoconstituents against five potential targets of SARS-CoV-2 using in silico structure-based virtual screening approach. Out of twenty five phytocomponents, ten components showed best binding affinity against two viral proteins viz. N-terminal RNA binding domain (NRBD; PDB ID: 6M3M) of nucleocapsid protein and papain-like protease (PL-PRO; PDB ID: 6W9C) of SARS-CoV-2 using AutoDock 4.2.6, AutoDock Vina and iGEMDOCK. PASS analyses of all ten phytocomponents using Lipinski's Rule of five showed promising results. Further, druglikeness and toxicity assessment using OSIRIS Data Warrior v5.2.1 software exhibited the feasibility of phytocomponents as drug candidates with no predicted toxicity. Molecular dynamics simulation study of NRBD of SARS-CoV-2 nucleocapsid protein-alpha-spinasterol complex and PL-PRO-cycloeucalenol complex displayed strong stability at 300 K. Both these complexes exhibited constant root mean square deviation (RMSDs) of protein side chains and Cα atoms throughout the simulation run time. Interestingly, PL-PRO and NRBD are key proteins in viral replication, host cell immune evasion and viral assembly. Thus, NRBD and PL-PRO have the potential to serve as therapeutic targets for N. sativa phytoconstituents in drug discovery process against COVID-19.

17.
J Biomol Struct Dyn ; 40(4): 1858-1908, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-947599

ABSTRACT

Coronaviruses are etiological agents of extreme human and animal infection resulting in abnormalities primarily in the respiratory tract. Presently, there is no defined COVID-19 intervention and clinical trials of prospective therapeutic agents are still in the nascent stage. Withania somnifera (L.) Dunal (WS), is an important medicinal plant in Ayurveda. The present study aimed to evaluate the antiviral potential of selected WS phytoconstituents against the novel SARS-CoV-2 target proteins and human ACE2 receptor using in silico methods. Most of the phytoconstituents displayed good absorption and transport kinetics and were also found to display no associated mutagenic or adverse effect(s). Molecular docking analyses revealed that most of the WS phytoconstituents exhibited potent binding to human ACE2 receptor, SAR-CoV and SARS-CoV-2 spike glycoproteins as well as the two main SARS-CoV-2 proteases. Most of the phytoconstituents were predicted to undergo Phase-I metabolism prior to excretion. All phytoconstituents had favorable bioactivity scores with respect to various receptor proteins and target enzymes. SAR analysis revealed that the number of oxygen atoms in the withanolide backbone and structural rearrangements were crucial for effective binding. Molecular simulation analyses of SARS-CoV-2 spike protein and papain-like protease with Withanolides A and B, respectively, displayed a stability profile at 300 K and constant RMSDs of protein side chains and Cα atoms throughout the simulation run time. In a nutshell, WS phytoconstituents warrant further investigations in vitro and in vivo to unravel their molecular mechanism(s) and modes of action for their future development as novel antiviral agents against COVID-19.


Subject(s)
COVID-19 , Withania , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Withania/chemistry
18.
Comput Struct Biotechnol J ; 18: 3402-3414, 2020.
Article in English | MEDLINE | ID: covidwho-919690

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is a novel beta coronavirus. SARS-CoV-2 uses spike glycoprotein to interact with host angiotensin-converting enzyme 2 (ACE2) and ensure cell recognition. High infectivity of SARS-CoV-2 raises questions on spike-ACE2 binding affinity and its neutralization by anti-SARS-CoV monoclonal antibodies (mAbs). Here, we observed Val-to-Lys417 mutation in the receptor-binding domains (RBD) of SARS-CoV-2, which established a Lys-Asp electrostatic interaction enhancing its ACE2-binding. Pro-to-Ala475 substitution and Gly482 insertion in the AGSTPCNGV-loop of RBD possibly hinders neutralization of SARS-CoV-2 by anti-SARS-CoV mAbs. In addition, we identified unique and structurally conserved conformational-epitopes on RBDs, which can be potential therapeutic targets. Collectively, we provide new insights into the mechanisms underlying the high infectivity of SARS-CoV-2 and development of effective neutralizing agents.

19.
Infect Genet Evol ; 85: 104583, 2020 11.
Article in English | MEDLINE | ID: covidwho-816816

ABSTRACT

The emergence of a new coronavirus, in around late December 2019 which had first been reported in Wuhan, China has now developed into a massive threat to global public health. The World Health Organization (WHO) has named the disease caused by the virus as COVID-19 and the virus which is the culprit was renamed from the initial novel respiratory 2019 coronavirus to SARS-CoV-2. The person-to-person transmission of this virus is ongoing despite drastic public health mitigation measures such as social distancing and movement restrictions implemented in most countries. Understanding the source of such an infectious pathogen is crucial to develop a means of avoiding transmission and further to develop therapeutic drugs and vaccines. To identify the etiological source of a novel human pathogen is a dynamic process that needs comprehensive and extensive scientific validations, such as observed in the Middle East respiratory syndrome (MERS), severe acute respiratory syndrome (SARS), and human immunodeficiency virus (HIV) cases. In this context, this review is devoted to understanding the taxonomic characteristics of SARS-CoV-2 and HIV. Herein, we discuss the emergence and molecular mechanisms of both viral infections. Nevertheless, no vaccine or therapeutic drug is yet to be approved for the treatment of SARS-CoV-2, although it is highly likely that new effective medications that target the virus specifically will take years to establish. Therefore, this review reflects the latest repurpose of existing antiviral therapeutic drug choices available to combat SARS-CoV-2.


Subject(s)
COVID-19/epidemiology , HIV Infections/epidemiology , HIV/classification , SARS-CoV-2/classification , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , China , Drug Repositioning , HIV/genetics , HIV/immunology , HIV Infections/drug therapy , HIV Infections/virology , Humans , Pandemics/prevention & control , Phylogeny , SARS-CoV-2/genetics , SARS-CoV-2/immunology
SELECTION OF CITATIONS
SEARCH DETAIL