Furin Inhibitors Block SARS-CoV-2 Spike Protein Cleavage to Suppress Virus Production and Cytopathic Effects

Cell Reports, Journal Year: 2020, Volume and Issue: 33(2), P. 108254 - 108254

Published: Sept. 23, 2020

Development of specific antiviral agents is an urgent unmet need for SARS-coronavirus 2 (SARS-CoV-2) infection. This study focuses on host proteases that proteolytically activate the SARS-CoV-2 spike protein, critical its fusion after binding to angiotensin-converting enzyme (ACE2), as targets. We first validate cleavage at a putative furin substrate motif spikes by expressing it in VeroE6 cells and find prominent syncytium formation. Cleavage are abolished treatment with inhibitors decanoyl-RVKR-chloromethylketone (CMK) naphthofluorescein, but not transmembrane protease serine (TMPRSS2) inhibitor camostat. CMK naphthofluorescein show effects SARS-CoV-2-infected decreasing virus production cytopathic effects. Further analysis reveals that, similar camostat, blocks entry, further suppresses syncytium. Naphthofluorescein acts primarily suppressing viral RNA transcription. Therefore, may be promising prevention

Language: Английский

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Wuhan to World: The COVID-19 Pandemic

Frontiers in Cellular and Infection Microbiology, Journal Year: 2021, Volume and Issue: 11

Published: March 30, 2021

COVID-19 is a Severe Acute Respiratory Syndrome (SARS), caused by SARS-CoV-2, novel virus which belongs to the family Coronaviridae . It was first reported in December 2019 Wuhan city of China and soon after, hence disease got spread entire world. As February 26, 2021, SARS-CoV-2 has infected ~112.20 million people ~2.49 deaths across globe. Although case fatality rate among patient lower (~2.15%) than its earlier relatives, SARS-CoV (~9.5%) MERS-CoV (~34.4%), been observed be more infectious higher morbidity mortality worldwide. now, only knowledge regarding potential transmission routes rapidly developed diagnostics guiding world for managing indicating an immediate need detailed understanding pathogen disease-biology. Over very short period time, researchers have generated lot information unprecedented ways key areas, including viral entry into host, dominant mutation, routes, diagnostic targets their detection assays, therapeutic drug molecules inhibiting and/or replication host cross-neutralizing antibodies vaccine candidates that could help us combat ongoing pandemic. In current review, we summarized available about disease, COVID-19. We believe this readily base would serve as valuable resource scientific clinical community may faster development solution disease.

Language: Английский

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Response to the Novel Corona Virus (COVID-19) Pandemic Across Africa: Successes, Challenges, and Implications for the Future

Frontiers in Pharmacology, Journal Year: 2020, Volume and Issue: 11

Published: Sept. 11, 2020

The COVID-19 pandemic has already claimed considerable lives. There are major concerns in Africa due to existing high prevalence rates for both infectious and non-infectious diseases limited resources terms of personnel, beds equipment. Alongside this, that lockdown other measures will have on prevention management non-communicable (NCDs). NCDs an increasing issue with rising morbidity mortality rates. World Health Organization (WHO) warns a lack nets treatment could result up 18 million additional cases malaria 30,000 deaths sub-Saharan Africa.

Language: Английский

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One year update on the COVID-19 pandemic: Where are we now?

Acta Tropica, Journal Year: 2020, Volume and Issue: 214, P. 105778 - 105778

Published: Nov. 28, 2020

Language: Английский

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Clinical manifestation and disease progression in COVID-19 infection

Journal of the Chinese Medical Association, Journal Year: 2020, Volume and Issue: 84(1), P. 3 - 8

Published: Nov. 24, 2020

Coronavirus disease 2019 (COVID-19) is mainly an infectious of the respiratory system transmitted through air droplets, and pulmonary symptoms constitute main presentations this disease. However, COVID-19 demonstrates a clinically diverse manifestation ranging from asymptomatic presentation to critically illness with severe pneumonia, acute distress syndrome, failure, or multiple organ failure. Accumulating evidences demonstrated that has extrapulmonary involvement, including neurological, smelling sensation, cardiovascular, digestive, hepatobiliary, renal, endocrinologic, dermatologic system, others. Over third patients manifest wide range neurological involving central/peripheral nervous system. Underlying cardiovascular comorbidities were associated detrimental outcomes, meanwhile occurrence complications correlate poor survival. Gastrointestinal frequently occur have been longer period illness. Impaired hepatic functions severity Higher rate kidney injury was reported in ill COVID-19. Endocrinologic include exacerbating hyperglycemia, euglycemic ketosis, diabetic ketoacidosis. The most common cutaneous acro-cutaneous (pernio chilblain-like) lesions, other skin lesions consist maculopapular rash, vesicular livedoid/necrotic exanthematous rashes, petechiae. This review article summarized general clinical signs symptoms, radiologic features, progression

Language: Английский

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Mechanism of inflammatory response in associated comorbidities in COVID-19

Diabetes & Metabolic Syndrome Clinical Research & Reviews, Journal Year: 2020, Volume and Issue: 14(4), P. 597 - 600

Published: May 12, 2020

Language: Английский

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Rethinking the role of hydroxychloroquine in the treatment of COVID‐19

The FASEB Journal, Journal Year: 2020, Volume and Issue: 34(5), P. 6027 - 6037

Published: April 29, 2020

There are currently no proven or approved treatments for coronavirus disease 2019 (COVID-19). Early anecdotal reports and limited in vitro data led to the significant uptake of hydroxychloroquine (HCQ), lesser extent chloroquine (CQ), many patients with this disease. As an increasing number COVID-19 treated these agents more evidence accumulates, there continues be high-quality clinical showing a clear benefit Moreover, have potential cause harm, including broad range adverse events serious cardiac side effects when combined other agents. In addition, known potent immunomodulatory which support their use treatment auto-immune conditions, provided component original rationale COVID-19, may, fact, undermine utility context respiratory viral infection. Specifically, impact HCQ on cytokine production suppression antigen presentation may immunologic consequences that hamper innate adaptive antiviral immune responses COVID-19. Similarly, reported inhibition proliferation is largely derived from blockade fusion initiates infection rather than direct replication as seen nucleoside/tide analogs infections. Given facts growing uncertainty about it at very least thoughtful planning collection randomized trials needed understand what if any role article, we review datasets detract render informed opinion they should only used caution carefully thought out trials, case-by-case basis after rigorous consideration risks benefits therapeutic approach.

Language: Английский

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An Updated Review of Computer‐Aided Drug Design and Its Application to COVID‐19

BioMed Research International, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

The recent outbreak of the deadly coronavirus disease 19 (COVID‐19) pandemic poses serious health concerns around world. lack approved drugs or vaccines continues to be a challenge and further necessitates discovery new therapeutic molecules. Computer‐aided drug design has helped expedite development process by minimizing cost time. In this review article, we highlight two important categories computer‐aided (CADD), viz., ligand‐based as well structured‐based discovery. Various molecular modeling techniques involved in structure‐based are docking dynamic simulation, whereas includes pharmacophore modeling, quantitative structure‐activity relationship (QSARs), artificial intelligence (AI). We have briefly discussed significance context COVID‐19 how researchers continue rely on these computational rapid identification promising candidate molecules against various targets implicated pathogenesis severe acute respiratory syndrome 2 (SARS‐CoV‐2). structural elucidation pharmacological preclinical accelerated both design. This article will help clinicians exploit immense potential designing thereby helping management fatal disease.

Language: Английский

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A review on drug repurposing applicable to COVID-19

Briefings in Bioinformatics, Journal Year: 2020, Volume and Issue: 22(2), P. 726 - 741

Published: Oct. 4, 2020

Drug repurposing involves the identification of new applications for existing drugs at a lower cost and in shorter time. There are different computational drug-repurposing strategies some these approaches have been applied to coronavirus disease 2019 (COVID-19) pandemic. Computational drug-repositioning COVID-19 can be broadly categorized into (i) network-based models, (ii) structure-based (iii) artificial intelligence (AI) approaches. Network-based divided two categories: clustering propagation Both them allowed annotate important patterns, identify proteins that functionally associated with discover novel drug-disease or drug-target relationships useful therapies. Structure-based small chemical compounds able bind macromolecular targets evaluate how compound interact biological counterpart, trying find drugs. AI-based networks appear, moment, less relevant since they need more data their application.

Language: Английский

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A narrative literature review on traditional medicine options for treatment of corona virus disease 2019 (COVID-19)

Complementary Therapies in Clinical Practice, Journal Year: 2020, Volume and Issue: 40, P. 101214 - 101214

Published: June 17, 2020

Language: Английский

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