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1.
J Ambient Intell Humaniz Comput ; : 1-10, 2021 May 15.
Article in English | MEDLINE | ID: covidwho-2242373

ABSTRACT

Around the world, more than 250 countries are affected by the COVID-19 pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This outbreak can be controlled only by the diagnosis of the COVID-19 infection in early stages. It is found that the radiographic images are ideal for the fastest diagnosis of COVID-19 infection. This paper proposes an ensemble model which detects the COVID-19 infection in the early stage with the use of chest X-ray images. The transfer learning enables to reuse the pretrained models. The ensemble learning integrates various transfer learning models, i.e., EfficientNet, GoogLeNet, and XceptionNet, to design the proposed model. These models can categorize patients as COVID-19 (+), pneumonia (+), tuberculosis (+), or healthy. The proposed model enhances the classifier's generalization ability for both binary and multiclass COVID-19 datasets. Two popular datasets are used to evaluate the performance of the proposed ensemble model. The comparative analysis validates that the proposed model outperforms the state-of-art models in terms of various performance metrics.

2.
Curr Pharmacol Rep ; 6(4): 137-145, 2020.
Article in English | MEDLINE | ID: covidwho-1797390

ABSTRACT

Purpose of Review: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, is a pandemic causing havoc globally. Currently, there are no Food and Drug Administration (FDA)-approved drugs to treat COVID-19. In the absence of effective treatment, off-label drug use, in lieu of evidence from published randomized, double-blind, placebo-controlled clinical trials, is common in COVID-19. Although it is vital to treat affected patients with antiviral drugs, there is a knowledge gap regarding the use of anti-inflammatory drugs in these patients. Recent Findings: Colchicine trials to combat inflammation in COVID-19 patients have not received much attention. We await the results of ongoing colchicine randomized controlled trials in COVID-19, evaluating colchicine's efficacy in treating COVID-19. Summary: This review gives a spotlight on colchicine's anti-inflammatory and antiviral properties and why colchicine may help fight COVID-19. This review summarizes colchicine's mechanism of action via the tubulin-colchicine complex. Furthermore, it discussed how colchicine interferes with several inflammatory pathways, including inhibition of neutrophil chemotaxis, adhesion, and mobilization; disruption of superoxide production, inflammasome inhibition, and tumor necrosis factor reduction; and its possible antiviral properties. In addition, colchicine dosing and pharmacokinetics, as well as drug interactions and how they relate to ongoing, colchicine in COVID-19 clinical trials, are examined.

3.
J Mol Struct ; 1229: 129489, 2021 Apr 05.
Article in English | MEDLINE | ID: covidwho-2095816

ABSTRACT

The COVID-19 pandemic, caused by SARS CoV-2, is responsible for millions of death worldwide. No approved/proper therapeutics is currently available which can effectively combat this outbreak. Several attempts have been undertaken in the search of effective drugs to control the spread of SARS CoV-2 infection. The main protease (Mpro), key component for the cleavage of the viral polyprotein, is considered to be one of the important drug targets for treating COVID-19. Various phytochemicals, including polyphenols and alkaloids, have been proposed as potent inhibitors of Mpro. The alkaloids from leaf extracts of Justicia adhatoda have also been reported to possess anti-viral activity. But whether these alkaloids exhibit any inhibitory effect on SARS CoV-2 Mpro is far from clear. To explore this in detail, we have adopted computational approaches. Justicia adhatoda alkaloids possessing proper drug-likeness properties and two anti-HIV drugs (lopinavir and darunavir; having binding affinity -7.3 to -7.4 kcal/mol) were docked against SARS CoV-2 Mpro to study their binding properties. Only one alkaloid (anisotine) had interaction with both the catalytic residues (His41 and Cys145) of Mpro and exhibited good binding affinity (-7.9 kcal/mol). Molecular dynamic simulations (100 ns) revealed that Mpro-anisotine complex is more stable, conformationally less fluctuated; slightly less compact and marginally expanded than Mpro-darunavir/lopinavir complex. Even the number of intermolecular H-bonds and MM-GBSA analysis suggested that anisotine is a more potent Mpro inhibitor than the two previously recommended antiviral drugs (lopinavir and darunavir) and may evolve as a promising anti-COVID-19 drug if proven in animal experiments and on patients.

4.
J Policy Pract Intellect Disabil ; 17(3): 256-269, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1949684

ABSTRACT

The current COVID-19 pandemic is a pressing world crisis and people with intellectual disabilities (IDs) are vulnerable due to disparity in healthcare provision and physical and mental health multimorbidity. While most people will develop mild symptoms upon contracting severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), some will develop serious complications. The aim of this study is to present guidelines for the care and treatment of people with IDs during the COVID-19 pandemic for both community teams providing care to people with IDs and inpatient psychiatric settings. The guidelines cover specific issues associated with hospital passports, individual COVID-19 care plans, the important role of families and carers, capacity to make decisions, issues associated with social distancing, ceiling of care/treatment escalation plans, mental health and challenging behavior, and caring for someone suspected of contracting or who has contracted SARS-CoV-2 within community or inpatient psychiatric settings. We have proposed that the included conditions recommended by Public Health England to categorize someone as high risk of severe illness due to COVID-19 should also include mental health and challenging behavior. There are specific issues associated with providing care to people with IDs and appropriate action must be taken by care providers to ensure that disparity of healthcare is addressed during the COVID-19 pandemic. We recognize that our guidance is focused upon healthcare delivery in England and invite others to augment our guidance for use in other jurisdictions.

5.
Environ Chem Lett ; 19(1): 17-24, 2021.
Article in English | MEDLINE | ID: covidwho-1906117

ABSTRACT

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 14 million people globally. Recently, airborne transmission has been postulated to be a major contributor to the spread of the novel coronavirus, especially in enclosed public spaces. While many studies have demonstrated positive correlations between atmospheric pollutants and SARS-CoV-2 infection, the impact of indoor air pollutants on airborne transmission has been largely overlooked. In particular, laser printers are a primary source of particle emission that increases the concentrations of particulate matter in indoor atmosphere by releasing substantial quantities of electrostatic fine particles, at rates comparable with tobacco smoking and incense burning. We hypothesized that particles emitted from laser printers present a potential risk factor for the transmission of SARS-CoV-2 in offices and other indoor environments with high user occupancy. To test this hypothesis, we reviewed recent knowledge on the characteristics of particles emitted by laser printing, including their emission rates and accumulation in indoor air, electrostatic charges, localized emission and subsequent particle diffusion in relation to the human breathing zone. We then discuss the potential impact on the transmission of SAR-CoV-2 in indoor spaces. We found that emission rates from laser printers ranged from 108 to 1012 particles min-1, and these fine particles typically remain suspended for prolonged periods in indoor air. Electrostatic charges carried by these particles can reach 260-379 e per particle, thus enhancing their surface adsorption and deposition in human airways. Localized emission by laser printers and subsequent diffusion highly increase particle concentrations near the human breathing zone.

6.
Hepatol Commun ; 4(9): 1242-1256, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1898760

ABSTRACT

The recent outbreak of the novel virus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes the corona virus disease of 2019 (COVID19), has spread globally and affects millions of people. This pandemic has taxed our health care system and disrupted normal operations, even life-saving procedures, such as liver transplants. During these unprecedented times, providers and patients are imperiled and resources for diagnosis and care may be limited. Continuing to perform resource-intense advanced procedures is challenging, as is caring for patients with end-stage liver disease or patients with urgent needs for liver tumor control. Liver transplantation, in particular, requires critical resources, like blood products and critical care beds, which are fairly limited in the COVID19 pandemic. The potential of COVID19 infections in posttransplant recipients on immunosuppression and staff contacts further adds to the complexity. Therefore, transplant programs must reevaluate the ethicality, feasibility, and safety of performing liver transplants during this pandemic. Herein, we discuss the clinical and ethical challenges posed by performing liver transplants and offer guidance for managing patients with end-stage liver disease during the COVID19 pandemic.

7.
Ecol Evol ; 10(22): 12418-12422, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-1898642

ABSTRACT

The ongoing COVID-19 pandemic caused by SARS-CoV-2 has caused widespread deaths, illnesses, and societal disruption. I describe here how I pivoted a discussion-based senior biology capstone course to include a multiweek module surrounding one primary literature paper on the evolution of SARS-CoV-2 and the subsequent scientific discourse about the paper. Using a gradual reveal of the paper following the CREATE method (consider, read, elucidate, and think of the next experiment), I challenged students to learn new evolutionary principles and critically analyze the data surrounding the evolution and transmission of SARS-CoV-2 presented in the paper. I also provide general advice for implementing this module in future courses.

8.
Med Clin (Engl Ed) ; 155(6): 249-253, 2020 Sep 25.
Article in English | MEDLINE | ID: covidwho-1796343

ABSTRACT

PURPOSE: Influenza virus infection is associated with a high disease burden. COVID-19 caused by SARS-CoV-2 has become a pandemic outbreak since January 2020. Taiwan has effectively contained COVID-19 community transmission. We aimed to validate whether fighting COVID-19 could help to control other respiratory infections in Taiwan. METHOD: We collected week-case data of severe influenza, invasive Streptococcus pneumoniae disease and death toll from pneumonia among 25 calendar weeks of the influenza season for four years (2016-2020), which were reported to Taiwan CDC. Trend and slope differences between years were compared. RESULT: A downturn trend of severe influenza, invasive S. pneumoniae disease and the death toll from pneumonia per week in 2019/2020 season and significant trend difference in comparison to previous seasons were noted, especially after initiation of several disease prevention measures to fight potential COVID-19 outbreak in Taiwan. CONCLUSIONS: Fighting COVID-19 achieved collateral benefits on significant reductions of severe influenza burden, invasive S. pneumoniae disease activity, and the death toll from pneumonia reported to CDC in Taiwan.


PROPÓSITOS: La COVID-19, causada por SARS-CoV-2, se ha convertido en un brote de pandemia desde enero de 2020. Taiwán ha contenido efectivamente la transmisión comunitaria de la COVID-19. Por otra parte, la influenza también es una enfermedad que se asocia con una alta carga de morbilidades. El objetivo del estudio es validar si combatir la COVID-19 podría ayudar a controlar otras infecciones respiratorias en Taiwán. MÉTODOS: Recopilamos datos semanales de casos de influenza grave, infecciones invasivas por Streptococcus pneumoniae y número de muertes por neumonía, que se informaron a los CDC de Taiwán en las 25 semanas de la temporada de influenza durante 4 años (2016-2020). Comparamos las diferencias de tendencia y de pendiente entre los años. RESULTADOS: Se observó una tendencia a la baja de la influenza grave, de las infecciones invasivas por Streptococcus pneumoniae y del número de muertes por neumonía por semana en la temporada de influenza de 2019-2020. Se observaron diferencias significativas en la tendencia en comparación con las temporadas anteriores, especialmente después del inicio de varias medidas de prevención de enfermedades para combatir el posible brote de COVID-19 en Taiwán. CONCLUSIONES: Por el número de casos reportados a los CDC de Taiwán, encontramos que la lucha contra la COVID-19 logró beneficios colaterales en cuanto a reducción significativa de la carga de la influenza grave, a las infecciones invasivas por Streptococcus pneumoniae y al número de muertes por neumonía.

9.
PeerJ ; 8: e9357, 2020.
Article in English | MEDLINE | ID: covidwho-1791913

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared a pandemic by the World Health Organization, and the identification of effective therapeutic strategy is a need of the hour to combat SARS-CoV-2 infection. In this scenario, the drug repurposing approach is widely used for the rapid identification of potential drugs against SARS-CoV-2, considering viral and host factors. METHODS: We adopted a host transcriptome-based drug repurposing strategy utilizing the publicly available high throughput gene expression data on SARS-CoV-2 and other respiratory infection viruses. Based on the consistency in expression status of host factors in different cell types and previous evidence reported in the literature, pro-viral factors of SARS-CoV-2 identified and subject to drug repurposing analysis based on DrugBank and Connectivity Map (CMap) using the web tool, CLUE. RESULTS: The upregulated pro-viral factors such as TYMP, PTGS2, C1S, CFB, IFI44, XAF1, CXCL2, and CXCL3 were identified in early infection models of SARS-CoV-2. By further analysis of the drug-perturbed expression profiles in the connectivity map, 27 drugs that can reverse the expression of pro-viral factors were identified, and importantly, twelve of them reported to have anti-viral activity. The direct inhibition of the PTGS2 gene product can be considered as another therapeutic strategy for SARS-CoV-2 infection and could suggest six approved PTGS2 inhibitor drugs for the treatment of COVID-19. The computational study could propose candidate repurposable drugs against COVID-19, and further experimental studies are required for validation.

10.
SN Compr Clin Med ; 2(9): 1430-1435, 2020.
Article in English | MEDLINE | ID: covidwho-1682606

ABSTRACT

The current outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) also known as coronavirus disease 2019 (COVID-19) has quickly progressed to a global pandemic. There are well-documented cardiac complications of COVID-19 in patients with and without prior cardiovascular disease. The cardiac complications include myocarditis, heart failure, and acute coronary syndrome resulting from coronary artery thrombosis or SARS-CoV-2-related plaque ruptures. There is growing evidence showing that arrhythmias are also one of the major complications. Myocardial inflammation caused by viral infection leads to electrophysiological and structural remodeling as a possible mechanism for arrhythmia. This could also be the mechanism through which SARS-CoV-2 leads to different arrhythmias. In this review article, we discuss arrhythmia manifestations in COVID-19.

11.
Physiol Rep ; 9(11): e14800, 2021 06.
Article in English | MEDLINE | ID: covidwho-1268434

ABSTRACT

The objective of this review is to give an overview of the pathophysiological effects of the Coronavirus Disease 2019 (COVID-19) in relation to hypertension (HT), with a focus on the Renin-Angiotensin-Aldosterone System (RAAS) and the MAS receptor. HT is a multifactorial disease and a public health burden, as it is a risk factor for diseases like stroke, coronary artery disease, and heart failure, leading to 10.4 million deaths yearly. Blood pressure is regulated by the RAAS. The system consists of two counter-regulatory axes: ACE/ANG-II/AT1 R and ACE2/ANG-(1-7)/MAS. The main regulatory protein in balancing the RAAS is angiotensin-converting enzyme 2 (ACE2). The protein also functions as the main mediator of endocytosis of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the host cell. SARS-CoV-2 is the cause of COVID-19 and has caused a worldwide pandemic; however, the treatment and prophylaxis of COVID-19 are limited. Several drugs and vaccines are currently being tested in clinical trials with a few already approved by EMA and FDA. HT is a major risk factor regarding the severity and fatality of COVID-19, and the RAAS plays an important role in COVID-19 infection since SARS-CoV-2 can lead to a dysregulation of the system by reducing the ACE2 expression. The exact mechanisms of HT in relation to COVID-19 remain uncertain, and more research is needed for further elucidation.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/physiopathology , Hypertension/virology , Renin-Angiotensin System/physiology , COVID-19/epidemiology , COVID-19/virology , Humans , Hypertension/physiopathology , Pandemics , Risk Factors , SARS-CoV-2/isolation & purification
12.
Front Physiol ; 12: 653045, 2021.
Article in English | MEDLINE | ID: covidwho-1268280

ABSTRACT

Background: Tobacco smoking is known to be involved in the pathogenesis of several cardiopulmonary diseases. Additionally, smokers are highly susceptible to infectious agents due to weakened immunity. However, the progression of lung injury based on SARS-CoV-2-mediated COVID-19 pathogenesis amongst smokers and those with pre-existing pulmonary diseases is not known. We determined the systemic levels and activity of COVID-19 associated proteins, cytokine/chemokines, and lipid mediators (lipidomics) amongst COVID-19 patients with and without a history of smoking to understand the underlying susceptible factor in the pathogenesis of COVID-19. Methods: We obtained serum from healthy (CoV-), COVID-19 positive (CoV+), and COVID-19 recovered (CoV Rec) subjects with and without a history of smoking. We conducted a Luminex multiplex assay (cytokine levels), LC/MS (eicosanoids or oxylipin panel), and ACE2 enzymatic activity assays on the serum samples to determine the systemic changes in COVID-19 patients. Results: On comparing the levels of serum ACE2 amongst COVID-19 (positive and recovered) patients and healthy controls, we found a pronounced increase in serum ACE2 levels in patients with COVID-19 infection. Furthermore, ACE2 enzyme activity was significantly increased amongst COVID-19 patients with a smoking history. Also, we analyzed the levels of Angiotensin 1-7 (Ang1-7) peptide, the product of enzymatic action of ACE2, in the serum samples. We found significantly high levels of Ang1-7 in the serum of both CoV+ and CoV Rec patients. Our data further demonstrated a smoking-induced increase in serum furin and inflammatory cytokine [IFNγ(p = 0.0836), Eotaxin (p < 0.05), MCP-1 (p < 0.05), and IL-9 (p = 0.0991)] levels in COVID-19 patients as compared to non-smoking controls. Overall, our results show that smoking adversely affects the levels of systemic inflammatory markers and COVID-19 associated proteins, thus suggesting that COVID-19 infection may have severe outcomes amongst smokers.

13.
Front Endocrinol (Lausanne) ; 12: 677701, 2021.
Article in English | MEDLINE | ID: covidwho-1268244

ABSTRACT

Background: Angiotensin-converting enzyme II (ACE2), a receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) to enter host cells, is widely expressed in testes and prostate tissues. The testis and prostate produce semen. At present, there are contradictory reports about whether SARS-CoV-2 can exist in the semen of infected men. Objective: To provide a comprehensive overview of the topic of whether COVID-19 can impact on male reproductive system. Methods: We reviewed the relevant publications on the possible impact of Coronavirus Disease 2019 (COVID-19) on male reproductive system and summarized the latest and most important research results so far. Literature published in English from December 2019 to January 31, 2021 regarding the existence of SARS-CoV-2 in semen, testis, and prostatic fluid and the effects of COVID-19 on male reproductive were included. Results: We identified 28 related studies, only one of which reported the presence of SARS-CoV-2 in semen. The study found that the semen quality of patients with moderate infection was lower than that of patients with mild infection and healthy controls. The impaired semen quality may be related to fever and inflammation. Pathological analysis of the testis/epididymis showed that SARS-CoV-2 viral particles were positive in 10 testicular samples, and the spermatogenic function of the testis was impaired. All 94 expressed prostatic secretion (EPS) samples were negative for SARS-CoV-2 RNA. Conclusion: The likelihood of SARS-CoV-2 in the semen of COVID-19 patients is very small, and semen should rarely be regarded as a carrier of SARS-CoV-2 genetic material. However, COVID-19 may cause testicular spermatogenic dysfunction via immune or inflammatory reactions. Long-term follow-up is needed for COVID-19 male patients and fetuses conceived during the father's infection period.


Subject(s)
COVID-19/physiopathology , Genitalia, Male/virology , SARS-CoV-2/physiology , COVID-19/complications , COVID-19/pathology , Genitalia, Male/pathology , Genitalia, Male/physiology , History, 21st Century , Humans , Inflammation/complications , Inflammation/pathology , Inflammation/virology , Male , Prostate/pathology , Prostate/physiology , Prostate/virology , Semen/virology , Semen Analysis , Sexual Dysfunction, Physiological/pathology , Sexual Dysfunction, Physiological/virology , Testis/pathology , Testis/physiology , Testis/virology
14.
Front Cardiovasc Med ; 8: 644095, 2021.
Article in English | MEDLINE | ID: covidwho-1268239

ABSTRACT

Coronavirus disease 2019 (COVID-19), triggered by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), may lead to extrapulmonary manifestations like diabetes mellitus (DM) and hyperglycemia, both predicting a poor prognosis and an increased risk of death. SARS-CoV-2 infects the pancreas through angiotensin-converting enzyme 2 (ACE2), where it is highly expressed compared to other organs, leading to pancreatic damage with subsequent impairment of insulin secretion and development of hyperglycemia even in non-DM patients. Thus, this review aims to provide an overview of the potential link between COVID-19 and hyperglycemia as a risk factor for DM development in relation to DM pharmacotherapy. For that, a systematic search was done in the database of MEDLINE through Scopus, Web of Science, PubMed, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), and Wanfang Data. Data obtained underline that SARS-CoV-2 infection in DM patients is more severe and associated with poor clinical outcomes due to preexistence of comorbidities and inflammation disorders. SARS-CoV-2 infection impairs glucose homeostasis and metabolism in DM and non-DM patients due to cytokine storm (CS) development, downregulation of ACE2, and direct injury of pancreatic ß-cells. Therefore, the potent anti-inflammatory effect of diabetic pharmacotherapies such as metformin, pioglitazone, sodium-glucose co-transporter-2 inhibitors (SGLT2Is), and dipeptidyl peptidase-4 (DPP4) inhibitors may mitigate COVID-19 severity. In addition, some antidiabetic agents and also insulin may reduce SARS-CoV-2 infectivity and severity through the modulation of the ACE2 receptor expression. The findings presented here illustrate that insulin therapy might seem as more appropriate than other anti-DM pharmacotherapies in the management of COVID-19 patients with DM due to low risk of uncontrolled hyperglycemia and diabetic ketoacidosis (DKA). From these findings, we could not give the final conclusion about the efficacy of diabetic pharmacotherapy in COVID-19; thus, clinical trial and prospective studies are warranted to confirm this finding and concern.

15.
Front Cell Infect Microbiol ; 11: 680728, 2021.
Article in English | MEDLINE | ID: covidwho-1268238

ABSTRACT

The pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to more than 117 million reported cases and 2.6 million deaths. Accurate diagnosis technologies are vital for controlling this pandemic. Reverse transcription (RT)-based nucleic acid detection assays have been developed, but the strict sample processing requirement of RT has posed obstacles on wider applications. This study established a ligation and recombinase polymerase amplification (L/RPA) combined assay for rapid detection of SARS-CoV-2 on genes N and ORF1ab targeting the specific biomarkers recommended by the China CDC. Ligase-based strategies usually have a low-efficiency problem on RNA templates. This study has addressed this problem by using a high concentration of the T4 DNA ligase and exploiting the high sensitivity of RPA. Through selection of the ligation probes and optimization of the RPA primers, the assay achieved a satisfactory sensitivity of 101 viral RNA copies per reaction, which was comparable to RT-quantitative polymerase chain reaction (RT-qPCR) and other nucleic acid detection assays for SARS-CoV-2. The assay could be finished in less than 30 min with a simple procedure, in which the requirement for sophisticated thermocycling equipment had been avoided. In addition, it avoided the RT procedure and could potentially ease the requirement for sample processing. Once validated with clinical samples, the L/RPA assay would increase the practical testing availability of SARS-CoV-2. Moreover, the principle of L/RPA has an application potential to the identification of concerned mutations of the virus.


Subject(s)
COVID-19 , Recombinases , China , Humans , Nucleic Acid Amplification Techniques , RNA, Viral/genetics , SARS-CoV-2 , Sensitivity and Specificity
16.
Mol Cell Biol ; 41(9): e0018521, 2021 08 24.
Article in English | MEDLINE | ID: covidwho-1268135

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic, responsible for millions of deaths globally. Even with effective vaccines, SARS-CoV-2 will likely maintain a hold in the human population through gaps in efficacy, percent vaccinated, and arising new strains. Therefore, understanding how SARS-CoV-2 causes widespread tissue damage and the development of targeted pharmacological treatments will be critical in fighting this virus and preparing for future outbreaks. Herein, we summarize the progress made thus far by using in vitro or in vivo models to investigate individual SARS-CoV-2 proteins and their pathogenic mechanisms. We have grouped the SARS-CoV-2 proteins into three categories: host entry, self-acting, and host interacting. This review focuses on the self-acting and host-interacting SARS-CoV-2 proteins and summarizes current knowledge on how these proteins promote virus replication and disrupt host systems, as well as drugs that target the virus and virus interacting host proteins. Encouragingly, many of these drugs are currently in clinical trials for the treatment of COVID-19. Future coronavirus outbreaks will most likely be caused by new virus strains that evade vaccine protection through mutations in entry proteins. Therefore, study of individual self-acting and host-interacting SARS-CoV-2 proteins for targeted therapeutic interventions is not only essential for fighting COVID-19 but also valuable against future coronavirus outbreaks.


Subject(s)
Antiviral Agents/pharmacology , Host-Pathogen Interactions/drug effects , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Viral Proteins/metabolism , COVID-19 Vaccines/pharmacology , Drug Development , Humans , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/metabolism , Viral Proteins/chemistry , Viral Proteins/genetics , Virus Internalization , Virus Replication/drug effects , Virus Replication/physiology , COVID-19 Drug Treatment
17.
Brief Bioinform ; 22(6)2021 11 05.
Article in English | MEDLINE | ID: covidwho-1268068

ABSTRACT

The rapid spread and huge impact of the COVID-19 pandemic caused by the emerging SARS-CoV-2 have driven large efforts for sequencing and analyzing the viral genomes. Mutation analyses have revealed that the virus keeps mutating and shows a certain degree of genetic diversity, which could result in the alteration of its infectivity and pathogenicity. Therefore, appropriate delineation of SARS-CoV-2 genetic variants enables us to understand its evolution and transmission patterns. By focusing on the nucleotides that co-substituted, we first identified 42 co-mutation modules that consist of at least two co-substituted nucleotides during the SARS-CoV-2 evolution. Then based on these co-mutation modules, we classified the SARS-CoV-2 population into 43 groups and further identified the phylogenetic relationships among groups based on the number of inconsistent co-mutation modules, which were validated with phylogenetic trees. Intuitively, we tracked tempo-spatial patterns of the 43 groups, of which 11 groups were geographic-specific. Different epidemic periods showed specific co-circulating groups, where the dominant groups existed and had multiple sub-groups of parallel evolution. Our work enables us to capture the evolution and transmission patterns of SARS-CoV-2, which can contribute to guiding the prevention and control of the COVID-19 pandemic. An interactive website for grouping SARS-CoV-2 genomes and visualizing the spatio-temporal distribution of groups is available at https://www.jianglab.tech/cmm-grouping/.


Subject(s)
COVID-19/genetics , Evolution, Molecular , Genome, Viral/genetics , SARS-CoV-2/genetics , COVID-19/virology , Genetic Variation/genetics , Humans , Mutation/genetics , Pandemics , Phylogeny , SARS-CoV-2/pathogenicity , Whole Genome Sequencing
18.
Virulence ; 12(1): 1597-1609, 2021 12.
Article in English | MEDLINE | ID: covidwho-1268053

ABSTRACT

The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 is continuing to spread globally. SARS-CoV-2 infections of feline and canine species have also been reported. However, it is not entirely clear to what extent natural SARS-CoV-2 infection of pet dogs and cats is in households. We have developed enzyme-linked immunosorbent assays (ELISAs) using recombinant SARS-CoV-2 nucleocapsid (N) protein and the receptor-binding-domain (RBD) of the spike protein, and the SARS-CoV-2 spike-pseudotyped vesicular stomatitis virus (VSV)-based neutralization assay to screen serum samples of 239 pet cats and 510 pet dogs in Minnesota in the early phase of the COVID-19 pandemic from mid-April to early June 2020 for evidence of SARS-CoV-2 exposures. A cutoff value was used to identify the seropositive samples in each experiment. The average seroprevalence of N- and RBD-specific antibodies in pet cats were 8% and 3%, respectively. Among nineteen (19) N-seropositive cat sera, fifteen (15) exhibited neutralizing activity and seven (7) were also RBD-seropositive. The N-based ELISA is also specific and does not cross react with antigens of common feline coronaviruses. In contrast, SARS-CoV-2 antibodies were detected at a very low percentage in pet dogs (~ 1%) and were limited to IgG antibodies against SARS-CoV-2 N protein with no neutralizing activities. Our results demonstrate that SARS-CoV-2 seropositive rates are higher in pet cats than in pet dogs in MN early in the pandemic and that SARS-CoV-2 N-specific IgG antibodies can detect SARS-CoV-2 infections in companion animals with higher levels of specificity and sensitivity than RBD-specific IgG antibodies in ELISA-based assays.


Subject(s)
COVID-19 Serological Testing/veterinary , COVID-19/veterinary , Pets/virology , SARS-CoV-2/isolation & purification , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/diagnosis , COVID-19/epidemiology , Cats , Coronavirus Nucleocapsid Proteins/immunology , Coronavirus, Feline/immunology , Coronavirus, Feline/isolation & purification , Dogs , Enzyme-Linked Immunosorbent Assay/veterinary , Minnesota/epidemiology , Phosphoproteins/immunology , SARS-CoV-2/immunology , Sensitivity and Specificity , Seroepidemiologic Studies , Spike Glycoprotein, Coronavirus/immunology
19.
J Med Virol ; 93(10): 5729-5741, 2021 10.
Article in English | MEDLINE | ID: covidwho-1267466

ABSTRACT

The global coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an unprecedented worldwide public health emergency. Despite the concerted efforts of the scientific field, by April 25, 2021, SARS-CoV-2 had spread to over 192 countries/regions, causing more than 146 million confirmed cases including 31 million deaths. For now, an established treatment for patients with COVID-19 remains unavailable. The key to tackling this pandemic is to understand the mechanisms underlying its infectivity and pathogenicity. As a predominant focus, the coronavirus spike (S) protein is the key determinant of host range, infectivity, and pathogenesis. Thereby comprehensive understanding of the sophisticated structure of SARS-CoV-2 S protein may provide insights into possible intervention strategies to fight this ongoing global pandemic. Herein, we summarize the current knowledge of the molecular structural and functional features of SARS-CoV-2 S protein as well as recent updates on the cell entry mechanism of the SARS-CoV-2, paving the way for exploring more structure-guided strategies against SARS-CoV-2.


Subject(s)
SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , COVID-19/virology , Host Specificity , Humans , Mutation , Protein Conformation , Protein Subunits , Receptors, Virus/genetics , Receptors, Virus/metabolism , SARS-CoV-2/classification , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics , Virus Internalization
20.
Cancer Med ; 10(13): 4424-4436, 2021 07.
Article in English | MEDLINE | ID: covidwho-1267448

ABSTRACT

BACKGROUND: Infection with SARS-CoV-2 leads to COVID-19, the course of which is highly variable and depends on numerous patient-specific risk factors. Patients with tumor diseases are considered to be more susceptible to severe COVID-19; however, they also represent a heterogeneous group of individuals with variable risk. Identifying specific risk factors for a severe course of COVID-19 in patients with cancer is of great importance. METHODS: Patients diagnosed with solid tumors or hematological malignancies and PCR-confirmed SARS-CoV-2 infection were included into the multicentric ADHOK (Arbeitsgemeinschaft der Hämatologen und Onkologen im Krankenhaus e.V.) coronavirus tumor registry. Detailed information about the patients' cancer disease, treatment, and laboratory parameters prior to infection, was collected retrospectively. The outcome of the SARS-CoV-2 infection was graded according to the WHO. RESULTS: A total of 195 patients (68% with solid neoplasms and 32% with hematological malignancies) were included in the registry. Overall, the course of the SARS-CoV-2 infection varied greatly, as 69% of all patients were either asymptomatic or encountered a mild to moderate course, while 23% of the cohort died from COVID-19. In multivariable analysis, preinfection laboratory parameters (determined at least 10 days and a median of 21 days before the first documentation of SARS-CoV-2 infection) significantly correlated with severe course of the disease. Out of these, the absolute neutrophil count prior to infection showed the strongest association with COVID-19-related death. CONCLUSION: The course of COVID-19 in patients with tumor diseases is highly variable. Preinfection laboratory parameters may aid to identify patients at risk for severe COVID-19 at an early stage prior to infection with the virus. German Clinical Trials Register identification: DRKS00023012.


Subject(s)
Biomarkers/blood , COVID-19/mortality , Neoplasms/virology , Neutrophils/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/immunology , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Neoplasms/immunology , Neoplasms/mortality , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Young Adult
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