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1.
Applied Intelligence ; : 1-17, 2022.
Article in English | EuropePMC | ID: covidwho-1837580

ABSTRACT

In wake of COVID-19, the world has adapted to a new order. People have started wearing mask on their faces to prevent getting infected. The present face recognition models are no longer proving to be efficient in the current circumstances. This is because, most of the informative part of the face is covered by mask. The periocular recognition therefore holds the key to future of face recognition. However, the periocular region proves to be insufficiently enough to generate highly discriminative features. Also, most of the pre-COVID-19 algorithms fail to work in cases, where the number of training images available is very less. We propose a lightweight periocular recognition framework that uses thermo-visible features and ensemble subspace network classifier to improve upon the existing periocular recognition systems named as Masked Mobile Lightweight Thermo-visible Face Recognition (MmLwThV). The framework successfully improves the accuracy over a single visible modality by mitigating the effect of noise present in the thermo-visible features. The experiments on WHU-IIP dataset and an in-house collected dataset named, CVBL masked dataset, successfully validate the efficacy of our proposed framework. The MmLwFR framework is lightweight and can be easily deployed on mobile phones with a visible and an infrared camera.

2.
Indian J Ophthalmol ; 70(5): 1780-1786, 2022 05.
Article in English | MEDLINE | ID: covidwho-1835158

ABSTRACT

Purpose: To evaluate the retinal microvascular changes in patients, recovered from severe COVID-19 during the second wave of the pandemic in North India. Methods: In this observational cross-sectional study, 70 eyes of 35 patients who recovered from severe COVID-19 during the second wave underwent detailed ophthalmic evaluation 4-6 weeks after discharge. Twelve controls were also enrolled, and the difference in the findings between the case and control groups on optical coherence tomography (OCTA) were studied. Result: The ages of study participants ranged from 27 to 60 years with the male:female ratio being 1.05:1. The fundus changes suggestive of ischemia in the form of cotton wool spots and vascular tortuosity were seen in 25 eyes (35.71%). Increased venous tortuosity was the most common finding seen in 23 eyes (32.85%), of which 10 eyes (28.57%) had concurrent hypertensive retinopathy (HTR) changes. There was a significant reduction in the mean vascular density (VD) and perfusion density (PD) for both the superficial capillary plexus (SCP) and deep capillary plexus (DCP) at inner, outer ring, and whole (P < 0.05). Foveal avascular zone was significantly enlarged in both the SCP (P = 0.01) and the DCP (P = 0.03). The mean ganglion cell-inner plexiform layer (GC-IPL) was significantly reduced in comparison to controls (P < 0.001). Conclusion: Severe COVID-19 can result in microvascular changes at the macula in the form of reduction in vascular and perfusion density, which can be evaluated using OCTA. As structural changes precede functional changes, a close watch is recommended in patients showing compromise in retinal microvasculature.


Subject(s)
COVID-19 , Macula Lutea , Adult , COVID-19/complications , COVID-19/epidemiology , Female , Fluorescein Angiography/methods , Humans , Male , Middle Aged , Retinal Vessels/diagnostic imaging , Tomography, Optical Coherence/methods
3.
Drug Discov Today ; 27(7): 2015-2027, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1704646

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has generated a critical need for treatments to reduce morbidity and mortality associated with this disease. However, traditional drug development takes many years, which is not practical solution given the current pandemic. Therefore, a viable option is to repurpose existing drugs. The structural data of several proteins vital for the virus became available shortly after the start of the pandemic. In this review, we discuss the importance of these targets and their available potential inhibitors predicted by the computational approaches. Among the hits identified by computational approaches, 35 candidates were suggested for further evaluation, among which ten drugs are in clinical trials (Phase III and IV) for treating Coronavirus 2019 (COVID-19).


Subject(s)
COVID-19 , SARS-CoV-2 , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drug Repositioning , Humans , Molecular Docking Simulation
4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-314694

ABSTRACT

We have proposed an SEIR compartmental mathematical model. The prime objective of this study is to analyze and forecast the pandemic in Italy for the upcoming months. The basic reproduction number has been calculated. Based on the current situation in Italy, in this paper, we will estimate the possible time for the end of the pandemic in the country. The impact of lockdown and rapid isolation on the spread of the pandemic are also discussed. Further, we have studied four of the most pandemic affected regions in Italy. Using the proposed model, a prediction has been made about the duration of pandemic in these regions. The variation in the basic reproduction number corresponding to the sensitive parameters of the model is also examined.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-314693

ABSTRACT

A novel coronavirus, SARS-CoV-2 has caused a recent pandemic called COVID-19 and a severe health threat around the world. In the current situation, the virus is rapidly spreading worldwide, and the discovery of vaccine and potential therapeutics are critically essential. The crystal structure for main protease (Mpro) of SARS-CoV-2, 3-chymotrypsin-like cysteine protease (3CLpro) was recently made available and is considerably similar to previously reported SARS-CoV. Due to its essentiality in viral replication, it represents a potential drug target. Herein, computer-aided drug design (CADD) approach was implemented for the initial screening of 13 approved antiviral drugs. Molecular docking of 13 antivirals against 3-chymotrypsin-like cysteine protease (3CLpro) enzyme was accomplished and indinavir was described as a lead drug with a docking score of -8.824 and a XP Gscore of -9.466 kcal/mol. Indinavir possesses an important pharmacophore, hydroxyethylamine (HEA), and thus a new library of HEA compounds (>2500) was subjected to virtual screening that led to 25 hits with a docking score more than indinavir. Exclusively, compound 16 with docking score of -8.955 adhered to drug like parameters, and the Structure-Activity Relationship (SAR) analysis was demonstrated to highlight the importance of chemical scaffolds therein. Molecular Dynamics (MD) simulation studies carried out at 100ns supported the stability of 16 within the binding pocket. Largly, our results supported that this novel compound 16 binds to the domain I & II, and domain II-III linker of 3CLpro protein, suggesting its suitablity as strong candidate for therapeutic discovery against COVID-19. Lead compound 16 could pave incredible directions for the design of novel 3CLpro inhibitors and ultimately therapeutics against COVID-19 disease.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-314690

ABSTRACT

In the past few years, there has been an expeditious growth in the usage of social media platforms and blogging websites which has passed 3.8 billion marks of active users that use text as a prominentmeans for interactive communication. A fraction of users spread misinformation on social media. As Twitter has 330 million monthly active users, researchers have been using it as a source of data for misinformation identification. In this paper, we have proposed a Twitter dataset for fine-grained classification. Our dataset is consists of 1970 manually annotated tweets and is categorized into 4 misinformation classes, i.e, “Irrelevant”, “Conspiracy”, “True Information”, and “False Information” based on response erupted during COVID-19. In this work, we also generated useful insights on our dataset and performed a systematic analysis of various language models, namely, RNN (BiLSTM, LSTM), CNN (TextCNN), BERT , ROBERTA, and ALBERT for the classification task on our dataset. Through our work, we aim at contributing to the substantial efforts of the research community for the identification and mitigation of misinformation on the internet.

7.
Cureus ; 13(12), 2021.
Article in English | EuropePMC | ID: covidwho-1615379

ABSTRACT

Introduction: There has been a drastic reduction in the number of neurosurgeries performed during the COVID-19 pandemic due to a multitude of challenges prompting restructuring of neurosurgical services. The present study describes the challenges and outcomes of non-elective neurosurgical procedures done on COVID-19 positive patients along with the modifications in neurosurgical practice during the pandemic. Methods: A retrospective study was done in the Department of Neurosurgery over a period of one year and three months. Demographic and clinical details including outcomes of the COVID-19 positive patients, who had undergone non-elective neurosurgical interventions, were collected. Results: Ten patients (3.8%) were COVID-19 positive out of 262 neurosurgical interventions done. The age of the patients ranged from 5 days to 78 years with five males and five females. Out of the 10 patients, five were neurotrauma cases including one patient of head injury with craniovertebral junction injury. The patient with craniovertebral junction injury underwent foramen magnum decompression with C1 lateral mass-C2 pedicle screw on the right and C0-C2 pedicle screw and rod fixation on the left. The rest of the neurotrauma cases underwent craniotomy or burr-hole craniostomy followed by evacuation. Only one patient (10%) had postoperative 30-day mortality. The rest nine patients (90%) survived the post-operative 30-day mortality. The various modifications incorporated in the neurosurgical practice included categorizing the emergency room into various zones, a separate operating theatre for COVID-19 patients, limiting the number of operating members as well as minor modifications in the operating procedures. Conclusions: The postoperative surgical outcome is favorable in COVID-19 positive patients with modifications of the existing neurosurgical practices.

8.
Physics of fluids (Woodbury, N.Y. : 1994) ; 33(11), 2021.
Article in English | EuropePMC | ID: covidwho-1602371

ABSTRACT

The primary objective of this work is to investigate the mixing of droplets/aerosols, which originates from the sneezing/coughing (of possibly COVID-19 patient) with the ambient atmosphere. Effectively, we are studying the growth/decay of droplets/aerosols in the presence of inhomogeneous mixing, which focuses on the phenomena of entrainment of the (relatively) dry ambient air. We have varied the initial standard deviation, mean radius of the droplets/aerosols size distribution, and humidity of the ambient atmosphere to understand their effects on the final size spectra of droplets. Furthermore, a rigorous error analysis is carried out to understand the relative importance of these effects on the final spectra of droplets/aerosols. We find that these are vital parameters to determine the final spectra of droplets, which govern the broadening of the size spectra. Typically, broadening the size spectra of droplets/aerosols increases the probability of the virus-laden droplets/aerosols and thus could affect the transmission of infection in the ambient atmosphere.

9.
Ophthalmic Plast Reconstr Surg ; 38(3): 242-249, 2022.
Article in English | MEDLINE | ID: covidwho-1593635

ABSTRACT

PURPOSE: To correlate the clinical, radiological, and histopathological features in Covid-associated Rhino-orbito-cerebral mucormycosis cases presenting with acute visual loss. DESIGN: Cross-sectional study. METHODS: Covid-associated Rhino-orbito-cerebral mucormycosis cases with unilateral visual loss, planned for exenteration, underwent orbital and ophthalmological ocular examination. The available radiological sequences, doppler ultrasonography and histopathology findings were correlated with clinical manifestations. RESULTS: The median age was 51 years and the male: female ratio was 3:1. All except one presented with unilateral ophthalmoplegia. The ocular media were hazy in 2 eyes. In 8 eyes, retinal changes were suggestive of occlusion of CRA (6), combined occlusion of CRA and central retinal vein (1), and myopic degeneration with hypertensive retinopathy (1). The contralateral eye showed retinal ischemic changes in one patient. Radiological imaging showed orbital apex involvement in the 10 affected eyes and one contralateral eye. Ipsilateral cavernous sinus thrombosis, diffusion restriction on MRI of optic nerve, internal carotid artery narrowing/thrombosis, and cortical watershed infarcts were seen in 8, 4, 4, and 2 cases, respectively. The blood flow in CRA and ophthalmic artery was absent or reduced in all the 10 affected eyes and in 1 contralateral eye. On histopathology, orbital fat necrosis, fungal hyphae, acute inflammation, granuloma formation, ischemic thrombosis of ophthalmic artery was observed in 10 specimens. CRA was patent in 9 and thrombosed in 1 eye. Optic nerve was ischemic in 8 and viable in 2 eyes. CONCLUSION: Acute visual loss in ROCM cases is associated with orbital apex involvement and thrombotic ischemia of ophthalmic artery. Cessation of flow in CRA possibly occurs secondary to ophthalmic artery thrombosis.


Subject(s)
COVID-19 , Eye Infections, Fungal , Mucormycosis , Orbital Diseases , COVID-19/complications , Cross-Sectional Studies , Eye Infections, Fungal/complications , Eye Infections, Fungal/diagnosis , Eye Infections, Fungal/microbiology , Female , Humans , Male , Middle Aged , Mucormycosis/complications , Mucormycosis/diagnosis , Mucormycosis/microbiology , Orbital Diseases/etiology , Orbital Diseases/microbiology , Vision Disorders/diagnosis , Vision Disorders/etiology
10.
Phys Fluids (1994) ; 33(11): 115129, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1541309

ABSTRACT

The primary objective of this work is to investigate the mixing of droplets/aerosols, which originates from the sneezing/coughing (of possibly COVID-19 patient) with the ambient atmosphere. Effectively, we are studying the growth/decay of droplets/aerosols in the presence of inhomogeneous mixing, which focuses on the phenomena of entrainment of the (relatively) dry ambient air. We have varied the initial standard deviation, mean radius of the droplets/aerosols size distribution, and humidity of the ambient atmosphere to understand their effects on the final size spectra of droplets. Furthermore, a rigorous error analysis is carried out to understand the relative importance of these effects on the final spectra of droplets/aerosols. We find that these are vital parameters to determine the final spectra of droplets, which govern the broadening of the size spectra. Typically, broadening the size spectra of droplets/aerosols increases the probability of the virus-laden droplets/aerosols and thus could affect the transmission of infection in the ambient atmosphere.

11.
Acc Chem Res ; 54(19): 3643-3655, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1404866

ABSTRACT

Reliable, inexpensive, and rapid diagnostic tools are essential to control and prevent the spread of infectious diseases. Many commercial kits for coronavirus disease 2019 (COVID-19) diagnostics have played a crucial role in the fight against the COVID-19 pandemic. Most current standard in vitro diagnostic (IVD) protocols for infectious diseases are sensitive but time-consuming and require sophisticated laboratory equipment and specially trained personnel. Recent advances in biosensor technology suggest the potential to deliver point-of-care (POC) diagnostics that are affordable and provide accurate results in a short time. The ideal "sample-in-answer-out" type fully integrated POC infection diagnostic platforms are expected to be autonomous or easy-to-operate, equipment-free or infrastructure-independent, and high-throughput or easy to upscale. In this Account, we detail the recent progress made by our group and others in the development of centrifugal microfluidic devices or lab-on-a-disc (LOAD) systems. Unlike conventional pump-based fluid actuation, the centrifugal force generated by spinning the disc induces liquid pumping and no external fluidic interconnects are required. This allows a total fluidic network required for multiple steps of biological assays to be integrated on a disc, enabling fully automated POC diagnostics. Various applications have been demonstrated, including liquid biopsy for personalized cancer management, food applications, and environmental monitoring; here, we focus on IVD for infectious disease. First, we introduce various on-disc unit operation technologies, including reagent storage, sedimentation, filtration, valving, decanting, aliquoting, mixing, separation, serial dilution, washing, and calibration. Such centrifugal microfluidic technologies have already proved promising for micro-total-analysis systems for automated IVD ranging from molecular detection of pathogens to multiplexed enzyme-linked immunosorbent assays (ELISAs) that use raw samples such as whole blood or saliva. Some recent examples of LOAD systems for molecular diagnostics in which some or all steps of the assays are integrated on a disc, including pathogen enrichment, nucleic acid extraction, amplification, and detection, are discussed in detail. We then introduce fully automated ELISA systems with enhanced sensitivity. Furthermore, we demonstrate a toy-inspired fidget spinner that enables electricity-free and rapid analysis of pathogens from undiluted urine samples of patients with urinary tract infection symptoms and a phenotypic antimicrobial susceptibility test for an extreme POC diagnostics application. Considering the urgent need for cost-effective and reliable POC infection diagnostic tools, especially in the current pandemic crisis, the current limitations and future directions of fast and broad adaptation in real-world settings are also discussed. With proper attention to key challenges and leverage with recent advances in bio-sensing technologies, molecular biology, nanomaterials, analytical chemistry, miniaturization, system integration, and data management, LOAD systems hold the potential to deliver POC infection diagnostic tools with unprecedented performance regarding time, accuracy, and cost. We hope the new insight and promise of LOAD systems for POC infection diagnostics presented in this Account can spark new ideas and inspire further research and development to create better healthcare systems for current and future pandemics.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Point-of-Care Systems , Biosensing Techniques/methods , COVID-19/virology , COVID-19 Testing/instrumentation , Centrifugation , Humans , Lab-On-A-Chip Devices , RNA, Viral/analysis , RNA, Viral/isolation & purification , RNA, Viral/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification
12.
RSC Med Chem ; 12(10): 1757-1764, 2021 Oct 20.
Article in English | MEDLINE | ID: covidwho-1397905

ABSTRACT

NendoU (NSP15) is an Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond. Our in-house library was subjected to high throughput virtual screening (HTVS) to identify compounds with potential to inhibit NendoU enzyme, high-rank compounds (those that bound to multiple target structures) were further subjected to 100 nanoseconds MD simulations. Among these, one was found to be bound highly stable within the active site of the NendoU protein structure. Here, we are reporting a derivative of piperazine based '(2S,3S)-3-amino-1-(4-(4-(tert-butyl)benzyl)piperazin-1-yl)-4-phenylbutan-2-ol' (IV) from our in-house libraries having potential efficacy against SARS-CoV-2 in in vitro assays. This compound demonstrated inhibition of viral replication at the same level as Ivermectin, a known SARS-CoV-2 inhibitor, which is not used due to its toxicity at a higher than the currently approved dosage. Compound IV was not toxic to the cell lines up to a 50 µM concentration and exhibited IC50s of 4.97 µM and 8.46 µM in viral entry and spread assay, respectively. Therefore, this novel class of NendoU inhibitor could provide new insights for the development of treatment options for COVID-19.

13.
Bioorg Med Chem ; 47: 116393, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1385129

ABSTRACT

The continued toll of COVID-19 has halted the smooth functioning of civilization on a global scale. With a limited understanding of all the essential components of viral machinery and the lack of structural information of this new virus, initial drug discovery efforts had limited success. The availability of high-resolution crystal structures of functionally essential SARS-CoV-2 proteins, including 3CLpro, supports the development of target-specific therapeutics. 3CLpro, the main protease responsible for the processing of viral polypeptide, plays a vital role in SARS-CoV-2 viral replication and translation and is an important target in other coronaviruses. Additionally, 3CLpro is the target of repurposed drugs, such as lopinavir and ritonavir. In this study, target proteins were retrieved from the protein data bank (PDB IDs: 6 M03, 6LU7, 2GZ7, 6 W63, 6SQS, 6YB7, and 6YVF) representing different open states of the main protease to accommodate macromolecular substrate. A hydroxyethylamine (HEA) library was constructed from harvested chemical structures from all the series being used in our laboratories for screening against malaria and Leishmania parasites. The database consisted of ∼1000 structure entries, of which 70% were new to ChemSpider at the time of screening. This in-house library was subjected to high throughput virtual screening (HTVS), followed by standard precision (SP) and then extra precision (XP) docking (Schrodinger LLC 2021). The ligand strain and complex energy of top hits were calculated by Molecular Mechanics Generalized Born Surface Area (MM/GBSA) method. Promising hit compounds (n = 40) specifically binding to 3CLpro with high energy and average MM/GBSA scores were then subjected to (100-ns) MD simulations. Using this sequential selection followed by an in-silico validation approach, we found a promising HEA-based compound (N,N'-((3S,3'S)-piperazine-1,4-diylbis(3-hydroxy-1-phenylbutane-4,2-diyl))bis(2-(5-methyl-1,3-dioxoisoindolin-2-yl)-3-phenylpropanamide)), which showed high in vitro antiviral activity against SARS-CoV-2. Further to reduce the size of the otherwise larger ligand, a pharmacophore-based predicted library of âˆ¼42 derivatives was constructed, which were added to the previous compound library and rescreened virtually. Out of several hits from the predicted library, two compounds were synthesized, tested against SARS-CoV-2 culture, and found to have markedly improved antiviral activity.


Subject(s)
Antiviral Agents/chemistry , Coronavirus 3C Proteases/antagonists & inhibitors , Ethylamines/chemistry , Protease Inhibitors/chemistry , SARS-CoV-2/enzymology , Animals , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Binding Sites , COVID-19/pathology , COVID-19/virology , Catalytic Domain , Cell Survival/drug effects , Chlorocebus aethiops , Coronavirus 3C Proteases/metabolism , Ethylamines/metabolism , Ethylamines/pharmacology , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Protease Inhibitors/metabolism , Protease Inhibitors/pharmacology , SARS-CoV-2/isolation & purification , Thermodynamics , Vero Cells
14.
Clin Ophthalmol ; 15: 3505-3514, 2021.
Article in English | MEDLINE | ID: covidwho-1379902

ABSTRACT

PURPOSE: To list the clinico-epidemiological profile and possible risk factors of COVID-19 associated rhino-orbital-cerebral mucormycosis (CA-ROCM) patients presenting to a COVID dedicated hospital during the second wave of COVID-19 in India. PATIENTS AND METHODS: A cross-sectional, single-center study was done on 60 cases of probable CA-ROCM based on clinical features and supportive diagnostic nasal endoscopic findings and/or radiologic findings. Patients with recent or active COVID-19 were included. The demographic profile, clinical features, possible risk factors and diagnostic workup (microbiological, pathological and radiological) were analysed to identify the triggering factors for CA-ROCM. RESULTS: The age of patients ranged from 29 to 75 years and male-female ratio was 3:1. The duration between the first positive COVID report and onset of CA-ROCM was 0 to 47 days. Forty-nine (81.66%) patients had a recent COVID infection and 11 (18.33%) had active COVID infection at presentation. Thirty-five patients (58%) had ocular/orbital involvement at presentation. In the affected eye, 10 had no perception of light and in the rest visual acuity ranged from log MAR 0 to +1.5. Ocular manifestations were ptosis (29), ophthalmoplegia (23), periocular tenderness and edema (33), proptosis (14), black discoloration of eyelids (3), facial palsy (3), endophthalmitis (4), retinal artery occlusion (8), disc edema (4) and disc pallor (5). Twenty-two (25%) patients had neither received steroids nor oxygen. Thirty patients (50%) were managed with oxygen while 38 patients (63.3%) with systemic steroids. The most common risk factor was diabetes in 59 patients. The average glycosylated hemoglobin (HbA1c) was 10.31 ± 2.59%. Systemic Amphotericin B was started in all the patients. Radical surgical debridement was performed in 12 patients and the remaining were planned. CONCLUSION: SARS-CoV-2 variant with accompanying glycaemic dysregulation was found to be the triggering factor for the epidemic of CA-ROCM.

15.
Phys Fluids (1994) ; 33(7): 072004, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1310836

ABSTRACT

In this paper, the lifetime of coronavirus infected droplets under a stick-slip evaporation mode has been investigated, which may play a pivotal role in reducing the spread of COVID-19 infection. It is showed that the survival time of the virus can be reduced by increasing the receding contact angle or by reducing the initial contact angle of a drop deposited on a solid surface. It has been found that the lifetime of the virus increases almost five times under highly humid conditions as compared to dry conditions. It is further observed that the normalized lifetime does not depend upon thermo-physical properties, ambient temperature, relative humidity, and initial drop volume. A model has been proposed to estimate the shear stress acting on a virus taking into account the effect of a Marangoni flow. The presented model unveils that the magnitude of computed shear stress is not enough to obliterate the virus. The findings of the present model have been discussed in the context of reducing the COVID-19 infection, but the model can also be applied for coughed/sneezed droplets of other infectious diseases. Moreover, this physical understanding of evaporation dynamics on solid surfaces with a stick-slip mode may help in better design of a face mask, PPE kit, and other protective equipment used in public places in order to minimize the chances of infection and tackle the current pandemic. However, the reported model for estimating the survival time of the virus does not consider the effect of the thermo-capillary convection (the Marangoni effect).

16.
J Biomol Struct Dyn ; : 1-19, 2021 Jun 21.
Article in English | MEDLINE | ID: covidwho-1276045

ABSTRACT

For coronaviruses, RNA-dependent RNA polymerase (RdRp) is an essential enzyme that catalyses the replication from RNA template and therefore remains an attractive therapeutic target for anti-COVID drug discovery. In the present study, we performed a comprehensive in silico screening for 16,776 potential molecules from recently established drug libraries based on two important pharmacophores (3-amino-4-phenylbutan-2-ol and piperazine). Based on initial assessment, 4042 molecules were obtained suitable as drug candidates, which were following Lipinski's rule. Molecular docking implemented for the analysis of molecular interactions narrowed this number of compounds down to 19. Subsequent to screening filtering criteria and considering the critical parameters viz. docking score and MM-GBSA binding free energy, 1-(4-((2S,3S)-3-amino-2-hydroxy-4-phenylbutyl)piperazin-1-yl)-3-phenylurea (compound 1) was accomplished to score highest in comparison to the remaining 18 shortlisted drug candidates. Notably, compound 1 displayed higher docking score (-8.069 kcal/mol) and MM-GBSA binding free energy (-49.56 kcal/mol) than the control drug, remdesivir triphosphate, the active form of remdesivir as well as adenosine triphosphate. Furthermore, a molecular dynamics simulation was carried out (100 ns), which substantiated the candidacy of compound 1 as better inhibitor. Overall, our systematic in silico study predicts the potential of compound 1 to exhibit a more favourable specific activity than remdesivir triphosphate. Hence, we suggest compound 1 as a novel potential drug candidate, which should be considered for further exploration and validation of its potential against SARS-CoV-2 in wet lab experimental studies.Communicated by Ramasawamy H. Sarma.

17.
Ocul Immunol Inflamm ; 29(4): 690-696, 2021 May 19.
Article in English | MEDLINE | ID: covidwho-1223201

ABSTRACT

Purpose: To compare the cycle threshold (Ct) values of tears and nasopharyngeal (NP) swab in severe COVID-19 ICU patients with positive NP swabs.Procedure: A cross-sectional study for the detection of SARS-CoV-2 by real-time RT-PCR on simultaneously collected NP swabs and tears was performed. Detailed demographic profile, including comorbidities, ocular, and systemic features were analyzed.Results: In the 78 cases, the mean tear positivity was 26.92% (21/78), 2 tear samples being positive despite a negative NP swab. The mean Ct value of tears and NP were 28.17 ± 4.76 and 23.71 ± 6.19, respectively (p= .003). None of the cases had ocular findings or relationship between tear positivity and comorbidity.Conclusions: The viral load of tears is less than the NP secretions with the possibility of prolonged shedding in tears. Tears act as an additional source of contact transmission in ICU that can possibly be decreased by frequent hand hygiene by the patient.Abbreviations: SARS-CoV-2: Severe acute respiratory syndrome coronavirus; RT-PCR: Real-time Reverse transcriptase-polymerase chain reaction; COVID-19: Corona virus disease 2019; ICU: Intensive care unit; RdRp: RNA-dependent RNA polymerase; ORF 1b: Open reading frame 1b; AIIR: Airborne infection isolation room; HCW: Health care workers; VTM: viral transport media; NP: Nasopharyngeal swab; PPE: Personal protective equipment.


Subject(s)
COVID-19/virology , Intensive Care Units , Nasopharynx/virology , RNA, Viral/analysis , SARS-CoV-2/genetics , Tears/virology , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Specimen Handling , Viral Load , Young Adult
18.
Methods ; 195: 44-56, 2021 11.
Article in English | MEDLINE | ID: covidwho-1101546

ABSTRACT

Novel coronavirus SARS-CoV-2continues tospread rapidly worldwide and causing serious health and economic loss. In the absence of any effective treatment, various in-silico approaches are being explored towards the therapeutic discovery against COVID-19. Targeting multiple key enzymes of SARS-CoV-2 with a single potential drug could be an important in-silico strategy to tackle the therapeutic emergency. A number of Food and Drug Administration (FDA) approved drugs entered into clinical stages were originated from multi-target approaches with an increased rate, 16-21% between 2015 and 2017. In this study, we selected an FDA-approved library (Prestwick Chemical Library of 1520 compounds) and implemented in-silico virtual screening against multiple protein targets of SARS-CoV-2 on the Glide module of Schrödinger software (release 2020-1). Compounds were analyzed for their docking scores and the top-ranked against each targeted protein were further subjected to Molecular Dynamics (MD) simulations to assess the binding stability of ligand-protein complexes. A multi-targeting approach was optimized that enabled the analysis of several compounds' binding efficiency with more than one protein targets. It was demonstrated that Diosmin (6) showed the highest binding affinity towards multiple targets with binding free energy (kcal/mol) values of -63.39 (nsp3); -62.89 (nsp9); -31.23 (nsp12); and -65.58 (nsp15). Therefore, our results suggests that Diosmin (6) possesses multi-targeting capability, a potent inhibitor of various non-structural proteins of SARS-CoV-2, and thus it deserves further validation experiments before using as a therapeutic against COVID-19 disease.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Diosmin/pharmacology , Antiviral Agents/therapeutic use , COVID-19/virology , Coronavirus Papain-Like Proteases/antagonists & inhibitors , Coronavirus Papain-Like Proteases/metabolism , Coronavirus RNA-Dependent RNA Polymerase/antagonists & inhibitors , Coronavirus RNA-Dependent RNA Polymerase/metabolism , Diosmin/therapeutic use , Drug Discovery , Endoribonucleases/antagonists & inhibitors , Endoribonucleases/metabolism , Humans , Ligands , Molecular Docking Simulation , Molecular Dynamics Simulation , RNA-Binding Proteins , SARS-CoV-2/metabolism , Viral Nonstructural Proteins/antagonists & inhibitors , Viral Nonstructural Proteins/metabolism
19.
Nano Lett ; 21(1): 337-343, 2021 01 13.
Article in English | MEDLINE | ID: covidwho-1065789

ABSTRACT

Since the emergence of the COVID-19 pandemic outbreak, the increasing demand and disposal of surgical masks has resulted in significant economic costs and environmental impacts. Here, we applied a dual-channel spray-assisted nanocoating hybrid of shellac/copper nanoparticles (CuNPs) to a nonwoven surgical mask, thereby increasing the hydrophobicity of the surface and repelling aqueous droplets. The resulting surface showed outstanding photoactivity (combined photocatalytic and photothermal properties) for antimicrobial action, conferring reusability and self-sterilizing ability to the masks. Under solar illumination, the temperature of this photoactive antiviral mask (PAM) rapidly increased to >70 °C, generating a high level of free radicals that disrupted the membrane of nanosized (∼100 nm) virus-like particles and made the masks self-cleaning and reusable. This PAM design can provide significant protection against the transmission of viral aerosols in the fight against the COVID-19 pandemic.


Subject(s)
Antiviral Agents/chemistry , COVID-19/prevention & control , Copper/chemistry , Masks/virology , Metal Nanoparticles/chemistry , Sterilization/methods , Catalysis , Humans , Hydrophobic and Hydrophilic Interactions , Photochemical Processes , SARS-CoV-2/isolation & purification , Temperature
20.
ACS Appl Bio Mater ; 4(5): 3891-3908, 2021 05 17.
Article in English | MEDLINE | ID: covidwho-1061417

ABSTRACT

The outbreak of coronavirus disease (COVID-19) has transformed the daily lifestyles of people worldwide. COVID-19 was characterized as a pandemic owing to its global spread, and technologies based on engineered materials that help to reduce the spread of infections have been reported. Nanotechnology present in materials with enhanced physicochemical properties and versatile chemical functionalization offer numerous ways to combat the disease. Facemasks are a reliable preventive measure, although they are not 100% effective against viral infections. Nonwoven materials, which are the key components of masks, act as barriers to the virus through filtration. However, there is a high chance of cross-infection because the used mask lacks virucidal properties and can become an additional source of infection. The combination of antiviral and filtration properties enhances the durability and reliability of masks, thereby reducing the likelihood of cross-infection. In this review, we focus on masks, from the manufacturing stage to practical applications, and their abilities to combat COVID-19. Herein, we discuss the impacts of masks on the environment, while considering safe industrial production in the future. Furthermore, we discuss available options for future research directions that do not negatively impact the environment.


Subject(s)
Masks/trends , Nanotechnology/trends , Pandemics/prevention & control , COVID-19/prevention & control , COVID-19/transmission , Decontamination , Disease Transmission, Infectious , Equipment Design , Filtration , Humans , SARS-CoV-2 , Textiles
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