- On the use of ‘glyphmaps’ for analysing Covid-19 reported cases -
Recent analysis of area-level Covid-19 cases data attempts to grapple with a challenge familiar to geovisualization: how to capture the development of the virus, whilst supporting analysis across geographic areas? We present several glyphmap designs for addressing this challenge applied to local authority data in England whereby charts displaying multiple aspects related to the pandemic are given a geographic arrangement. These graphics are visually complex, with clutter, occlusion and salience bias an inevitable consequence. We develop a framework for systematically describing and validating the graphics against data and design requirements. Through an observational data analysis, we then relate designs to particular data analysis needs based on the usefulness of the structure they expose. Our designs, documented in an accompanying code repository, attend to common difficulties in geovisualization design and could transfer to contexts outside of the UK and to phenomena beyond the pandemic.
- Replicative fitness SARS-CoV-2 20I/501Y.V1 variant in a human reconstituted bronchial epithelium -
Since its emergence in 2019, circulating populations of the new coronavirus continuously acquired genetic diversity. At the end of 2020, a variant named 20I/501Y.V1 (lineage B.1.1.7) emerged and replaced other circulating strains in several regions. This phenomenon has been poorly associated to biological evidence that this variant and original strain exhibit different phenotypic characteristics. Here, we analyse the replication ability of this new variant in different cellular models using for comparison an ancestral D614G European strain (lineage B1). Results from comparative replication kinetics experiments in vitro and in a human reconstituted bronchial epithelium showed no difference. However, when both viruses were put in competition in a human reconstituted bronchial epithelium, the 20I/501Y.V1 variant outcompeted the ancestral strain. Altogether, these findings demonstrate that this new variant replicates more efficiently and could contribute to better understand the progressive replacement of circulating strains by the SARS-CoV-2 20I/501Y.V1 variant.
- Characterisation of B.1.1.7 and Pangolin coronavirus spike provides insights on the evolutionary trajectory of SARS-CoV-2 -
The recent emergence of SARS-CoV-2 variants with increased transmission, pathogenesis and immune resistance has jeopardised the global response to the COVID-19 pandemic. Determining the fundamental biology of viral variants and understanding their evolutionary trajectories will guide current mitigation measures, future genetic surveillance and vaccination strategies. Here we examine virus entry by the B.1.1.7 lineage, commonly referred to as the UK/Kent variant. Pseudovirus infection of model cell lines demonstrate that B.1.1.7 entry is enhanced relative to the Wuhan-Hu-1 reference strain, particularly under low expression of receptor ACE2. Moreover, the entry characteristics of B.1.1.7 were distinct from that of its predecessor strain containing the D614G mutation. These data suggest evolutionary tuning of spike protein function. Additionally, we found that amino acid deletions within the N-terminal domain (NTD) of spike were important for efficient entry by B.1.1.7. The NTD is a hotspot of diversity across sarbecoviruses, therefore, we further investigated this region by examining the entry of closely related CoVs. Surprisingly, Pangolin CoV spike entry was 50-100 fold enhanced relative to SARS-CoV-2; suggesting there may be evolutionary pathways by which SARS-CoV-2 may further optimise entry. Swapping the NTD between Pangolin CoV and SARS-CoV-2 demonstrates that changes in this region alone have the capacity to enhance virus entry. Thus, the NTD plays a hitherto unrecognised role in modulating spike activity, warranting further investigation and surveillance of NTD mutations.
- Differential effects of the second SARS-CoV-2 mRNA vaccine dose on T cell immunity in naive and COVID-19 recovered individuals -
The rapid development and deployment of mRNA-based vaccines against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the design of accelerated vaccination schedules that have been extremely effective in naive individuals. While a two-dose immunization regimen with the BNT162b2 vaccine has been demonstrated to provide a 95% efficacy in naive individuals, the effects of the second vaccine dose in individuals who have previously recovered from natural SARS-CoV-2 infection has been questioned. Here we characterized SARS-CoV-2 spike-specific humoral and cellular immunity in naive and previously infected individuals during full BNT162b2 vaccination. Our results demonstrate that the second dose increases both the humoral and cellular immunity in naive individuals. On the contrary, the second BNT162b2 vaccine dose results in a reduction of cellular immunity in COVID-19 recovered individuals, which suggests that a second dose, according to the current standard regimen of vaccination, may be not necessary in individuals previously infected with SARS-CoV-2.
- TMPRSS2 inhibitor discovery facilitated through an in silico and biochemical screening platform -
The COVID-19 pandemic has highlighted the need for new antiviral targets, as many of the currently approved drugs have proven ineffective against mitigating SARS-CoV-2 infections. The host transmembrane serine protease TMPRSS2 is a highly promising antiviral target, as it plays a direct role in priming the spike protein before viral entry occurs. Further, unlike other targets such as ACE2, TMPRSS2 has no known biological role. Here we utilize virtual screening to curate large libraries into a focused collection of potential inhibitors. Optimization of a recombinant expression and purification protocol for the TMPRSS2 peptidase domain facilitates subsequent biochemical screening and characterization of selected compounds from the curated collection in a kinetic assay. In doing so, we demonstrate that serine protease inhibitors camostat, nafamostat, and gabexate inhibit through a covalent mechanism. We further identify new non-covalent compounds as TMPRSS2 protease inhibitors, demonstrating the utility of a combined virtual and experimental screening campaign in rapid drug discovery efforts.
- Structural modeling of the SARS-CoV-2 Spike/human ACE2 complex interface can identify high-affinity variants associated with increased transmissibility -
The COVID-19 pandemic has triggered concerns about the emergence of more infectious and pathogenic viral strains. As a public health measure, efficient screening methods are needed to determine the functional effects of new sequence variants. Here we show that structural modeling of SARS-CoV-2 Spike protein binding to the human ACE2 receptor, the first step in host-cell entry, predicts many novel variant combinations with enhanced binding affinities. By focusing on natural variants at the Spike-hACE2 interface and assessing over 700 mutant complexes, our analysis reveals that high-affinity Spike mutations (including N440K, S443A, G476S, E484R, G502P) tend to cluster near known human ACE2 recognition sites (K31 and K353). These Spike regions are conformationally flexible, allowing certain mutations to optimize interface interaction energies. Although most human ACE2 variants tend to weaken binding affinity, they can interact with Spike mutations to generate high-affinity double mutant complexes, suggesting variation in individual susceptibility to infection. Applying structural analysis to highly transmissible variants, we find that circulating point mutations S447N, E484K and N501Y form high-affinity complexes (~40% more than wild-type). By combining predicted affinities and available antibody escape data, we show that fast-spreading viral variants exploit combinatorial mutations possessing both enhanced affinity and antibody resistance, including S447N/E484K, E484K/N501Y and K417T/E484K/N501Y. Thus, three-dimensional modeling of the Spike/hACE2 complex predicts changes in structure and binding affinity that correlate with transmissibility and therefore can help inform future intervention strategies.
- Live imaging of SARS-CoV-2 infection in mice reveals neutralizing antibodies require Fc function for optimal efficacy -
Neutralizing antibodies (NAbs) are effective in treating COVID-19 but the mechanism of immune protection is not fully understood. Here, we applied live bioluminescence imaging (BLI) to monitor the real-time effects of NAb treatment in prophylaxis and therapy of K18-hACE2 mice intranasally infected with SARS-CoV-2-nanoluciferase. We visualized sequential spread of virus from the nasal cavity to the lungs followed by systemic spread to various organs including the brain, culminating in death. Highly potent NAbs from a COVID-19 convalescent subject prevented, and also effectively resolved, established infection when administered within three days of infection. In addition to direct neutralization, in vivo efficacy required Fc effector functions of NAbs, with contributions from monocytes, neutrophils and natural killer cells, to dampen inflammatory responses and limit immunopathology. Thus, our study highlights the requirement of both Fab and Fc effector functions for an optimal in vivo efficacy afforded by NAbs against SARS-CoV-2.
- Predicting hosts based on early SARS-CoV-2 samples and analyzing later world-wide pandemic in 2020 -
The SARS-CoV-2 pandemic has raised the concern for identifying hosts of the virus since the early-stage outbreak. To address this problem, we proposed a deep learning method, DeepHoF, based on extracting the viral genomic features automatically, to predict host likelihood scores on five host types, including plant, germ, invertebrate, non-human vertebrate and human, for novel viruses. DeepHoF made up for the lack of an accurate tool applicable to any novel virus and overcame the limitation of the sequence similarity-based methods, reaching a satisfactory AUC of 0.987 on the five-classification. Additionally, to fill the gap in the efficient inference of host species for SARS-CoV-2 using existed tools, we conducted a deep analysis on the host likelihood profile calculated by DeepHoF. Using the isolates sequenced in the earliest stage of COVID-19, we inferred minks, bats, dogs and cats were potential hosts of SARS-CoV-2, while minks might be one of the most noteworthy hosts. Several genes of SARS-CoV-2 demonstrated their significance in determining the host range. Furthermore, the large-scale genome analysis, based on DeepHoF’s computation for the later world-wide pandemic in 2020, disclosed the uniformity of host range among SARS-CoV-2 samples and the strong association of SARS-CoV-2 between humans and minks.
- An mRNA vaccine against SARS-CoV-2: Lyophilized, liposome-based vaccine candidate EG-COVID induces high levels of virus neutralizing antibodies -
In addition to the traditional method of vaccine development, the mRNA coronavirus vaccine, which is attractive as a challenging vaccination, recently opened a new era in vaccinology. Here we describe the EG-COVID which is a novel liposome-based mRNA candidate vaccine that encodes the spike (S) protein of SARS-CoV-2 with 2P-3Q substitution in European variant. We developed the mRNA vaccine platform that can be lyophilized using liposome-based technology. Intramuscular injection of the EG-COVID elicited robust humoral and cellular immune response to SARS-CoV-2. Furthermore, sera obtained from mice successfully inhibited SARS-CoV-2 viral infection into Vero cells. We developed EG-COVID and found it to be effective based on in vitro data, and we plan to initiate a clinical trial soon. Since EG-COVID is a lyophilized mRNA vaccine that is convenient for transportation and storage, accessibility to vaccines will be significantly improved.
- Protease-activatable biosensors of SARS-CoV-2 infection for cell-based drug, neutralisation and virological assays -
The world is in the grip of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, and there is an urgent unmet clinical need for effective antiviral therapies. Many inhibitors of viral enzymes identified in vitro have limited efficacy against viral replication in cells, but conventional plaque assays are impractical for high-throughput screens. In this study, we therefore engineer cell-based biosensors of SARS-CoV-2 infection. Our assays exploit the cleavage of specific oligopeptide linkers by SARS-CoV-2 Main or Papain-like proteases, leading to the activation of green fluorescent protein (GFP) or firefly luciferase-based reporters. First, we characterise these biosensors in cells using recombinant viral proteases. Next, we confirm their ability to detect endogenous viral protease expression during infection with wildtype SARS-CoV-2. Finally, we develop a sensitive luminescent reporter cell line, confirm that it accurately quantitates infectious SARS-CoV-2 virus, and demonstrate its utility for drug screening and titration of neutralising antibodies.
- CVnCoV protects human ACE2 transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2 -
The ongoing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic necessitates the fast development of vaccines as the primary control option. Recently, viral mutants termed “variants of concern” (VOC) have emerged with the potential to escape host immunity. VOC B.1.351 was first discovered in South Africa in late 2020, and causes global concern due to poor neutralization with propensity to evade preexisting immunity from ancestral strains. We tested the efficacy of a spike encoding mRNA vaccine (CVnCoV) against the ancestral strain BavPat1 and the novel VOC B.1.351 in a K18-hACE2 transgenic mouse model. Naive mice and mice immunized with formalin-inactivated SARS-CoV-2 preparation were used as controls. mRNA-immunized mice developed elevated SARS-CoV-2 RBD-specific antibody as well as neutralization titers against the ancestral strain BavPat1. Neutralization titers against VOC B.1.351 were readily detectable but significantly reduced compared to BavPat1. VOC B.1.351-infected control animals experienced a delayed course of disease, yet nearly all SARS-CoV-2 challenged naive mice succumbed with virus dissemination and high viral loads. CVnCoV vaccine completely protected the animals from disease and mortality caused by either viral strain. Moreover, SARS-CoV-2 was not detected in oral swabs, lung, or brain in these groups. Only partial protection was observed in mice receiving the formalin-inactivated virus preparation. Despite lower neutralizing antibody titers compared to the ancestral strain BavPat1, CVnCoV shows complete disease protection against the novel VOC B.1.351 in our studies.
- Network medicine links SARS-CoV-2/COVID-19 infection to brain microvascular injury and neuroinflammation in dementia-like cognitive impairment -
Background: Dementia-like cognitive impairment is an increasingly reported complication of SARS-CoV-2 infection. However, the underlying mechanisms responsible for this complication remain unclear. A better understanding of causative processes by which COVID-19 may lead to cognitive impairment is essential for developing preventive interventions. Methods: In this study, we conducted a network-based, multimodal genomics comparison of COVID-19 and neurologic complications. We constructed the SARS-CoV-2 virus-host interactome from protein-protein interaction assay and CRISPR-Cas9 based genetic assay results, and compared network-based relationships therein with those of known neurological manifestations using network proximity measures. We also investigated the transcriptomic profiles (including single-cell/nuclei RNA-sequencing) of Alzheimer disease (AD) marker genes from patients infected with COVID-19, as well as the prevalence of SARS-CoV-2 entry factors in the brains of AD patients not infected with SARS-CoV-2. Results: We found significant network-based relationships between COVID-19 and neuroinflammation and brain microvascular injury pathways and processes which are implicated in AD. We also detected aberrant expression of AD biomarkers in the cerebrospinal fluid and blood of patients with COVID-19. While transcriptomic analyses showed relatively low expression of SARS-CoV-2 entry factors in human brain, neuroinflammatory changes were pronounced. In addition, single-nucleus transcriptomic analyses showed that expression of SARS-CoV-2 host factors (BSG and FURIN) and antiviral defense genes (LY6E, IFITM2, IFITM3, and IFNAR1) was significantly elevated in brain endothelial cells of AD patients and healthy controls relative to neurons and other cell types, suggesting a possible role for brain microvascular injury in COVID-19-mediated cognitive impairment. Notably, individuals with the AD risk allele APOE E4/E4 displayed reduced levels of antiviral defense genes compared to APOE E3/E3 individuals. Conclusion: Our results suggest significant mechanistic overlap between AD and COVID-19, strongly centered on neuroinflammation and microvascular injury. These results help improve our understanding of COVID-19-associated neurological manifestations and provide guidance for future development of preventive or treatment interventions.
- Immune characterization and profiles of SARS-CoV-2 infected patients reveals potential host therapeutic targets and SARS-CoV-2 oncogenesis mechanism -
The spread of SARS-CoV-2 and the increasing mortality rates of COVID-19 create an urgent need for treatments, which are currently lacking. Although vaccines have been approved by the FDA for emergency use in the U.S., patients will continue to require pharmacologic intervention to reduce morbidity and mortality as vaccine availability remains limited. The rise of new variants makes the development of therapeutic strategies even more crucial to combat the current pandemic and future outbreaks. Evidence from several studies suggests the host immune response to SARS-CoV-2 infection plays a critical role in disease pathogenesis. Consequently, host immune factors are becoming more recognized as potential biomarkers and therapeutic targets for COVID-19. To develop therapeutic strategies to combat current and future coronavirus outbreaks, understanding how the coronavirus hijacks the host immune system during and after the infection is crucial. In this study, we investigated immunological patterns or characteristics of the host immune response to SARS-CoV-2 infection that may contribute to the disease severity of COVID-19 patients. We analyzed large bulk RNASeq and single cell RNAseq data from COVID-19 patient samples to immunoprofile differentially expressed gene sets and analyzed pathways to identify human host protein targets. We observed an immunological profile of severe COVID-19 patients characterized by upregulated cytokines, interferon-induced proteins, and pronounced T cell lymphopenia, supporting findings by previous studies. We identified a number of host immune targets including PERK, PKR, TNF, NF-kB, and other key genes that modulate the significant pathways and genes identified in COVID-19 patients. Finally, we identified genes modulated by COVID-19 infection that are implicated in oncogenesis, including E2F transcription factors and RB1, suggesting a mechanism by which SARS-CoV-2 infection may contribute to oncogenesis. Further clinical investigation of these targets may lead to bonafide therapeutic strategies to treat the current COVID-19 pandemic and protect against future outbreaks and viral escape variants.
- Evolution and spread of SARS-CoV-2 likely to be affected by climate -
COVID-19 pandemic has been extensively studied by many researchers. However, it is still unclear why it was restricted to higher latitudes during the initial days and later cascaded in the tropics. Here, we analyzed 176 SARS-CoV-2 genomes across different latitudes and climate (Koppen climate) that provided insights about within species virus evolution and its relation to abiotic factors. Two genetically variant groups, named as G1 and G2 were identified, well defined by four mutations. The G1 group (ancestor), is mainly restricted to warm and moist, temperate climate (Koppen C climate) while its descendent G2 group surpasses the climatic restrictions of G1, initially cascading into neighboring cold climate (D) of higher latitudes and later into hot climate of the tropics (A). It appears that the gradation of temperate climate (Cfa-Cfb) to cold climate (Dfa-Dfb) drives the evolution of G1 into G2 variant group which later adapted to tropical climate (A) as well. It seems this virus followed inverse latitudinal gradient in the beginning due to its preference towards temperate (C) and cold climate (D). Our work elucidates virus evolutionary studies combined with climatic studies can provide crucial information about the pathogenesis and natural spreading pathways in such outbreaks which is hard to achieve through individual studies. Mutational insights gained may help design an efficacious vaccine.
- Show me the study! Science by press release is not science -
In this brief communication, the authors develop the argument that science by press release and by press conference without the readily available study for scrutiny is outside of the ethos of the scientific enterprise. Additionally, we argue why and how science by press conference and by press release is a recipe for misinformation and poor choices in public health decision-making fitting into the scope of your respectable journal. Finally, the authors dive into the implications of this emerging phenomenon for public health in Brazil in the COVID19 era.
Pilot Trial of XFBD, a TCM, in Persons With COVID-19 - Condition: Covid19
Interventions: Drug: Xuanfei Baidu Granules; Other: Placebo
Sponsor: Darcy Spicer
Recruiting
Safety and Tolerability of Emricasan in Symptomatic Outpatients Diagnosed With Mild-COVID-19 - Condition: Covid19
Interventions: Drug: Emricasan; Other: Placebo
Sponsor: Histogen
Recruiting
Efficacy of Reinforcing Standard Therapy in COVID-19 Patients With Repeated Transfusion of Convalescent Plasma - Condition: Covid19
Interventions: Other: Convalescent Plasma with antibody against SARS-CoV-2.; Other: Standard treatment for COVID-19
Sponsors: Hospital Son Llatzer; Fundació d’investigació Sanitària de les Illes Balears
Recruiting
ANTIcoagulation in Severe COVID-19 Patients - Condition: Severe COVID-19 Pneumonia
Interventions: Drug: Tinzaparin, Low dose prophylactic anticoagulation; Drug: Tinzaparin, High dose prophylactic anticoagulation; Drug: Tinzaparin,Therapeutic anticoagulation
Sponsor: Assistance Publique - Hôpitaux de Paris
Not yet recruiting
Neuromodulation in COVID-19 Patients - Condition: COVID-19
Interventions: Device: Transcranial direct-current stimulation; Device: Sham Transcranial direct-current stimulation
Sponsors: D’Or Institute for Research and Education; Rio de Janeiro State Research Supporting Foundation (FAPERJ); Conselho Nacional de Desenvolvimento Científico e Tecnológico; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
Not yet recruiting
Off-the-shelf NK Cells (KDS-1000) as Immunotherapy for COVID-19 - Condition: Covid19
Interventions: Biological: KDS-1000; Other: Placebo
Sponsor: Kiadis Pharma
Not yet recruiting
Corticosteroids for COVID-19 - Condition: Covid19
Interventions: Drug: Prednisone; Device: Point of Care testing device for C-reactive protein
Sponsor: University of Alberta
Not yet recruiting
Effects of Telerehabilitation After Discharge in COVID-19 Survivors - Condition: Covid19
Intervention: Other: Telerehabilitation
Sponsor: Hacettepe University
Recruiting
A Study to Assess if a Medicine Called Bamlanivimab is Safe and Effective in Reducing Hospitalization Due to COVID-19 - Condition: Covid19
Interventions: Biological: Bamlanivimab; Other: Standard of Care
Sponsors: Fraser Health; Fraser Health Authrority Department of Evaluation and Research Services; Surrey Memorial Hospital Clinical Research Unit; Centre for Health Evaluation and Outcome Sciences; Surrey Hospitals Foundation; BC Support Unit; University of British Columbia; Ministry of Health, British Columbia
Not yet recruiting
Efficacy of Adaptogens in Patients With Long COVID-19 - Condition: Covid19
Interventions: Dietary Supplement: ADAPT-232 oral solution; Other: Placebo oral solution
Sponsors: Swedish Herbal Institute AB; National Family Medicine Training Centre, Georgia; Tbilisi State Medical University; Phytomed AB
Not yet recruiting
COVID-19 Self-Testing Through Rapid Network Distribution - Condition: Covid19
Interventions: Behavioral: COVID-19 self-test; Behavioral: COVID-19 test referral
Sponsors: University of Pennsylvania; Public Health Management Corporation
Not yet recruiting
Effectiveness of the Adsorbed Vaccine COVID-19 (Coronavac) Among Education and Public Safety Workers With Risk Factors for Severity - Condition: Covid19
Intervention: Biological: Adsorbed SARS-CoV-2 (inactivated) vaccine
Sponsors: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado; Butantan Institute
Recruiting
Text-based Reminders to Promote COVID-19 Vaccinations - Condition: Covid19, Vaccines
Interventions: Behavioral: Self-benefit; Behavioral: Prosocial-benefit; Behavioral: Early access; Behavioral: Fresh start
Sponsors: University of California, Los Angeles; Carnegie Mellon University
Recruiting
Text-based Interventions to Promote COVID-19 Vaccinations - Condition: Covid19, Vaccines
Interventions: Behavioral: Patient MyChart Scheduling Link; Behavioral: Patient Educational Video; Behavioral: Enhanced Follow through Message
Sponsors: University of California, Los Angeles; Carnegie Mellon University
Recruiting
Efficacy of Psidii Guava’s Extract For COVID-19 - Condition: Covid19
Interventions: Drug: Extract Psidii guava; Combination Product: Standard therapy for Covid-19 patient
Sponsor: Faculty of Medicine Baiturrahmah University
Completed
DNA vaccine candidate encoding SARS-CoV-2 spike proteins elicited potent humoral and Th1 cell-mediated immune responses in mice - More than 65 million people have been confirmed infection with SARS-CoV-2 and more than 1 million have died from COVID-19 and this pandemic remains critical worldwide. Effective vaccines are one of the most important strategies to limit the pandemic. Here, we report a construction strategy of DNA vaccine candidates expressing full length wild type SARS-CoV-2 spike (S) protein, S1 or S2 region and their immunogenicity in mice. All DNA vaccine constructs of pCMVkan-S, -S1 and -S2 induced high…
Cross-linking peptide and repurposed drugs inhibit both entry pathways of SARS-CoV-2 - Up to date, effective antivirals have not been widely available for treating COVID-19. In this study, we identify a dual-functional cross-linking peptide 8P9R which can inhibit the two entry pathways (endocytic pathway and TMPRSS2-mediated surface pathway) of SARS-CoV-2 in cells. The endosomal acidification inhibitors (8P9R and chloroquine) can synergistically enhance the activity of arbidol, a spike-ACE2 fusion inhibitor, against SARS-CoV-2 and SARS-CoV in cells. In vivo studies indicate that…
Evaluation of the safety and efficacy of XAV-19 in patients with COVID-19-induced moderate pneumonia: study protocol for a randomized, double-blinded, placebo-controlled phase 2 (2a and 2b) trial - BACKGROUND: Early inhibition of entry and replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a very promising therapeutic approach. Polyclonal neutralizing antibodies offers many advantages such as providing immediate immunity, consequently blunting an early pro-inflammatory pathogenic endogenous antibody response and lack of drug-drug interactions. By providing immediate immunity and inhibiting entry into cells, neutralizing antibody treatment is of interest for…
A small molecule compound berberine as an orally active therapeutic candidate against COVID-19 and SARS: A computational and mechanistic study - The novel coronavirus disease, COVID-19, has grown into a global pandemic and a major public health threat since its breakout in December 2019. To date, no specific therapeutic drug or vaccine for treating COVID-19 and SARS has been FDA approved. Previous studies suggest that berberine, an isoquinoline alkaloid, has shown various biological activities that may help against COVID-19 and SARS, including antiviral, anti-allergy and inflammation, hepatoprotection against drug- and infection-induced…
Herbal Medicine in Fighting Against COVID-19: New Battle with an Old Weapon - World population has been suffering due to the outbreak of present pandemic situation of COVID-19. The disease has become life-threatening in a very short time with touching on most of the citizenry and economic systems globally. The novel virus, SARS-CoV-2 has been known as the causative agent of COVID-19. The SARS-CoV-2 is single stranded RNA virus having ~30 kb genomic components which are 70% identical to SARS-CoV. The main process of pathophysiology of COVID-19 has been associated with the…
On the search for COVID-19 therapeutics: identification of potential SARS-CoV-2 main protease inhibitors by virtual screening, pharmacophore modeling and molecular dynamics - COVID-19 also known as SARS-CoV-2 outbreak in late 2019 and its worldwide pandemic spread has taken the world by surprise. The minute-to-minute increasing coronavirus cases (>85 M) and progressive deaths (≈1.8 M) calls for finding a cure to this devastating pandemic. While there have been many attempts to find biologically active molecules targeting SARS-CoV-2 for treatment of this viral infection, none has found a way to the clinic yet. In this study, a 3-feature structure-based pharmacophore…
Phylogenic analysis of coronavirus genome and molecular studies on potential anti-COVID-19 agents from selected FDA-approved drugs - The emergence of 2019 novel Coronavirus (COVID-19 or 2019-nCoV) has caused significant global morbidity and mortality with no consensus specific treatment. We tested the hypothesis that FDA-approved antiretrovirals, antibiotics, and antimalarials will effectively inhibit COVID-19 two major drug targets, coronavirus nucleocapsid protein (NP) and hemagglutinin-esterase (HE). To test this hypothesis, we carried out a phylogenic analysis of coronavirus genome to understand the origins of NP and HE,…
Potential of CRISPR/Cas13 System in Treatment and Diagnosis of COVID-19 - The novel coronavirus disease 2019 (COVID-19) belongs to coronaviridae families like sarbecovirus (SARS), and causes pyrexia, pertussis, and acute respiratory distress syndrome (ARDS) in major. Started from Wuhan, China, COVID-19 now forced the World Health Organization (WHO) call it a global pandemic. These dreadful figures elevate the need for rapid action for a rapid diagnostic tool, an efficacious therapy, or vaccine for such widespread disease. In this article, we reviewed all the latest…
Evaluation of flavonoids as 2019-nCoV cell entry inhibitor through molecular docking and pharmacological analysis - The outbreak of Coronavirus Disease 2019 (COVID-19) has been declared as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO), which is being rapidly spread by the extremely spreadable and pathogenic 2019 novel coronavirus (2019-nCoV), also known as SARS-CoV-2. Pandemic incidence of COVID-19 has created a severe threat to global public health, necessitating the development of effective drugs or inhibitors or therapeutics agents against SARS-CoV-2….
Comprehensive analysis of SARS-CoV-2 antibody dynamics in New Zealand - CONCLUSION: Antibodies to SARS-CoV-2 persist for up to 8 months following mild-to-moderate infection. This robust response can be attributed to the initial exposure without immune boosting given the lack of community transmission in our setting.
RGD-binding integrins and TGF-beta in SARS-CoV-2 infections - novel targets to treat COVID-19 patients? - The new coronavirus SARS-CoV-2 is a global pandemic and a severe public health crisis. SARS-CoV-2 is highly contagious and shows high mortality rates, especially in elderly and patients with pre-existing medical conditions. At the current stage, no effective drugs are available to treat these patients. In this review, we analyse the rationale of targeting RGD-binding integrins to potentially inhibit viral cell infection and to block TGF-β activation, which is involved in the severity of several…
Acidic preconditioning reduces lipopolysaccharide-induced acute lung injury by upregulating the expression of angiotensin-converting enzyme 2 - Acid preconditioning (APC) through carbon dioxide inhalation can exert protective effects during acute lung injury (ALI) triggered by ischemia-reperfusion. Angiotensin-converting enzyme 2 (ACE2) has been identified as a receptor for severe acute respiratory syndrome coronavirus and the novel coronavirus disease-19. Downregulation of ACE2 plays an important role in the pathogenesis of severe lung failure after viral or bacterial infections. The aim of the present study was to examine the…
Molecular Mechanism of Action of Repurposed Drugs and Traditional Chinese Medicine Used for the Treatment of Patients Infected With COVID-19: A Systematic Scoping Review - Background: The emergence of COVID-19 as a pandemic has resulted in the need for urgent development of vaccines and drugs and the conduction of clinical trials to fight the outbreak. Because of the time constraints associated with the development of vaccines and effective drugs, drug repurposing and other alternative treatment methods have been used to treat patients that have been infected by the SARS-CoV-2 virus and have acquired COVID-19. Objective: The objective of this systematic scoping…
A review on function and side effects of systemic corticosteroids used in high-grade COVID-19 to prevent cytokine storms - In December 2019, a cluster of pneumonia caused by a novel coronavirus (2019-nCoV), officially known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, Hubei province, China. Cytokine storm is an uncontrolled systemic inflammatory response resulting from the release of large amounts of pro-inflammatory cytokines and chemokines that occurs at phase 3 of viral infection. Such emergence led to the development of many clinical trials to discover efficient drugs and…
A comprehensive insight into the role of zinc deficiency in the renin-angiotensin and kinin-kallikrein system dysfunctions in COVID-19 patients - Hypozincemia is prevalent in severe acute respiratory syndrome coronavirus-2 (SARS-COV-2)-infected patients and has been considered as a risk factor in severe coronavirus disease-2019 (COVID-19). Whereas zinc might affect SARS-COV-2 replication and cell entry, the link between zinc deficiency and COVID-19 severity could also be attributed to the effects of COVID-19 on the body metabolism and immune response. Zinc deficiency is more prevalent in the elderly and patients with underlying chronic…