scholarly journals Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michael G. Sugiyama ◽  
Haotian Cui ◽  
Dar’ya S. Redka ◽  
Mehran Karimzadeh ◽  
Edurne Rujas ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Drug Targets ◽  
Respiratory Infections ◽  
Antiviral Drug ◽  
Drug Repurposing ◽  
Human Coronavirus ◽  
Independent Manner ◽  
Convolutional Networks ◽  
Target Drug ◽  
Coronavirus Infection

AbstractThe COVID-19 pandemic has highlighted the urgent need for the identification of new antiviral drug therapies for a variety of diseases. COVID-19 is caused by infection with the human coronavirus SARS-CoV-2, while other related human coronaviruses cause diseases ranging from severe respiratory infections to the common cold. We developed a computational approach to identify new antiviral drug targets and repurpose clinically-relevant drug compounds for the treatment of a range of human coronavirus diseases. Our approach is based on graph convolutional networks (GCN) and involves multiscale host-virus interactome analysis coupled to off-target drug predictions. Cell-based experimental assessment reveals several clinically-relevant drug repurposing candidates predicted by the in silico analyses to have antiviral activity against human coronavirus infection. In particular, we identify the MET inhibitor capmatinib as having potent and broad antiviral activity against several coronaviruses in a MET-independent manner, as well as novel roles for host cell proteins such as IRAK1/4 in supporting human coronavirus infection, which can inform further drug discovery studies.

scholarly journals Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease

2021 ◽  
Author(s):  
Michael Sugiyama ◽  
Haotian Cui ◽  
Dar'ya S Redka ◽  
Mehran Karimzadeh ◽  
Edurne Rujas ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Drug Targets ◽  
Antiviral Drug ◽  
Drug Repurposing ◽  
Human Coronavirus ◽  
Independent Manner ◽  
Drug Candidates ◽  
Convolutional Networks ◽  
Target Drug ◽  
Coronavirus Infection

The COVID-19 pandemic has led to an urgent need for the identification of new antiviral drug therapies that can be rapidly deployed to treat patients with this disease. COVID-19 is caused by infection with the human coronavirus SARS-CoV-2. We developed a computational approach to identify new antiviral drug targets and repurpose clinically-relevant drug compounds for the treatment of COVID-19. Our approach is based on graph convolutional networks (GCN) and involves multiscale host-virus interactome analysis coupled to off-target drug predictions. Cell-based experimental assessment reveals several clinically-relevant repurposing drug candidates predicted by the in silico analyses to have antiviral activity against human coronavirus infection. In particular, we identify the MET inhibitor capmatinib as having potent and broad antiviral activity against several coronaviruses in a MET-independent manner, as well as novel roles for host cell proteins such as IRAK1/4 in supporting human coronavirus infection, which can inform further drug discovery studies.

scholarly journals An evidence-based systematic review on emerging therapeutic and preventive strategies to treat novel coronavirus (SARS-CoV-2) during an outbreak scenario

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Anupama M. Gudadappanavar ◽  
Jyoti Benni
Keyword(s):  
Antiviral Drug ◽  
Drug Repurposing ◽  
Respiratory Illness ◽  
World Health ◽  
Recombinant Vaccines ◽  
Subunit Vaccines ◽  
Coronavirus Infection ◽  
Novel Coronavirus ◽  
Health Organization ◽  
Full Length Genome

AbstractA novel coronavirus infection coronavirus disease 2019 (COVID-19) emerged from Wuhan, Hubei Province of China, in December 2019 caused by SARS-CoV-2 is believed to be originated from bats in the local wet markets. Later, animal to human and human-to-human transmission of the virus began and resulting in widespread respiratory illness worldwide to around more than 180 countries. The World Health Organization declared this disease as a pandemic in March 2020. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. Nevertheless, few broad-spectrum antiviral drugs have been studied against COVID-19 in clinical trials with clinical recovery. In the current review, we summarize the morphology and pathogenesis of COVID-19 infection. A strong rational groundwork was made keeping the focus on current development of therapeutic agents and vaccines for SARS-CoV-2. Among the proposed therapeutic regimen, hydroxychloroquine, chloroquine, remdisevir, azithromycin, toclizumab and cromostat mesylate have shown promising results, and limited benefit was seen with lopinavir–ritonavir treatment in hospitalized adult patients with severe COVID-19. Early development of SARS-CoV-2 vaccine started based on the full-length genome analysis of severe acute respiratory syndrome coronavirus. Several subunit vaccines, peptides, nucleic acids, plant-derived, recombinant vaccines are under pipeline. This article concludes and highlights ongoing advances in drug repurposing, therapeutics and vaccines to counter COVID-19, which collectively could enable efforts to halt the pandemic virus infection.

scholarly journals SAveRUNNER: A network-based algorithm for drug repurposing and its application to COVID-19

2021 ◽  
Vol 17 (2) ◽  
pp. e1008686
Author(s):  
Giulia Fiscon ◽  
Federica Conte ◽  
Lorenzo Farina ◽  
Paola Paci
Keyword(s):  
Drug Targets ◽  
De Novo ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Gene Set Enrichment Analysis ◽  
Thrombin Inhibitors ◽  
New Combination ◽  
Human Coronavirus ◽  
Human Interactome ◽  
Off Label

The novelty of new human coronavirus COVID-19/SARS-CoV-2 and the lack of effective drugs and vaccines gave rise to a wide variety of strategies employed to fight this worldwide pandemic. Many of these strategies rely on the repositioning of existing drugs that could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we presented a new network-based algorithm for drug repositioning, called SAveRUNNER (Searching off-lAbel dRUg aNd NEtwoRk), which predicts drug–disease associations by quantifying the interplay between the drug targets and the disease-specific proteins in the human interactome via a novel network-based similarity measure that prioritizes associations between drugs and diseases locating in the same network neighborhoods. Specifically, we applied SAveRUNNER on a panel of 14 selected diseases with a consolidated knowledge about their disease-causing genes and that have been found to be related to COVID-19 for genetic similarity (i.e., SARS), comorbidity (e.g., cardiovascular diseases), or for their association to drugs tentatively repurposed to treat COVID-19 (e.g., malaria, HIV, rheumatoid arthritis). Focusing specifically on SARS subnetwork, we identified 282 repurposable drugs, including some the most rumored off-label drugs for COVID-19 treatments (e.g., chloroquine, hydroxychloroquine, tocilizumab, heparin), as well as a new combination therapy of 5 drugs (hydroxychloroquine, chloroquine, lopinavir, ritonavir, remdesivir), actually used in clinical practice. Furthermore, to maximize the efficiency of putative downstream validation experiments, we prioritized 24 potential anti-SARS-CoV repurposable drugs based on their network-based similarity values. These top-ranked drugs include ACE-inhibitors, monoclonal antibodies (e.g., anti-IFNγ, anti-TNFα, anti-IL12, anti-IL1β, anti-IL6), and thrombin inhibitors. Finally, our findings were in-silico validated by performing a gene set enrichment analysis, which confirmed that most of the network-predicted repurposable drugs may have a potential treatment effect against human coronavirus infections.

Coronavirus Disease 2019: Virology and Drug Targets

2020 ◽  
Vol 20 ◽  
Author(s):  
Praveen Thaggikuppe Krishnamurthy
Keyword(s):  
High Throughput Screening ◽  
Drug Targets ◽  
Vaccine Development ◽  
Antiviral Drug ◽  
Drug Repurposing ◽  
Structural Proteins ◽  
Current Status ◽  
Approved Drugs ◽  
Viral Target ◽  
Fda Approved Drugs

: The Coronavirus Disease 2019, a pandemic caused by novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is seriously affecting global health and the economy. As the vaccine development takes time, the current research is focused on repurposing FDA approved drugs against the viral target proteins. This review discusses the current understanding of SARS-CoV-2 virology, its target structural proteins (S- glycoprotein), non-structural proteins (3- chymotrypsin-like protease, papain-like protease, RNA-dependent RNA polymerase, and helicase) and accessory proteins, drug discovery strategies (drug repurposing, artificial intelligence, and high-throughput screening), and the current status of antiviral drug development.

scholarly journals Network-based Drug Repurposing for Human Coronavirus

2020 ◽  
Author(s):  
Yadi Zhou ◽  
Yuan Hou ◽  
Jiayu Shen ◽  
Yin Huang ◽  
William Martin ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
De Novo ◽  
Antiviral Drug ◽  
Drug Repurposing ◽  
Drug Combinations ◽  
Human Protein ◽  
High Morbidity ◽  
Potential Drug ◽  
Protein Interactome

AbstractHuman Coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle east respiratory syndrome coronavirus (MERS-CoV), and 2019 novel coronavirus (2019-nCoV), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV. Drug repurposing, represented as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV-host interactome and drug targets in the human protein-protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV has the highest nucleotide sequence identity with SARS-CoV (79.7%) among the six other known pathogenic HCoVs. Specifically, the envelope and nucleocapsid proteins of 2019-nCoV are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. Using network proximity analyses of drug targets and known HCoV-host interactions in the human protein-protein interactome, we computationally identified 135 putative repurposable drugs for the potential prevention and treatment of HCoVs. In addition, we prioritized 16 potential anti-HCoV repurposable drugs (including melatonin, mercaptopurine, and sirolimus) that were further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. Finally, we showcased three potential drug combinations (including sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the ‘Complementary Exposure’ pattern: the targets of the drugs both hit the HCoV-host subnetwork, but target separate neighborhoods in the human protein-protein interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations toward future clinical trials for HCoVs.

scholarly journals Antiviral activity of Pacific oyster (Crassostrea gigas) hemolymph against a human coronavirus.

2021 ◽  
Author(s):  
Rebecca L Pedler ◽  
James Harris ◽  
Peter G Speck
Keyword(s):  
Antiviral Activity ◽  
Crassostrea Gigas ◽  
Pacific Oyster ◽  
Respiratory Infections ◽  
Human Coronavirus ◽  
Fold Reduction ◽  
Intracellular Stage

Coronaviruses can can cause severe respiratory infections in humans. This study aimed to assess the antiviral activity of Pacific oyster (Crassostrea gigas) hemolymph against a human coronavirus, HCoV-229E. An eight-fold reduction in infectivity of HCoV-229E on Huh-7 cells was observed in the presence of 10% C. gigas hemolymph. Antiviral activity of C. gigas hemolymph positively correlated with its concentration and appears to be active during an intracellular stage of HCoV-229E infection.

scholarly journals Synthesis and Anti-Chikungunya Virus (CHIKV) Activity of Novel 1,4-Naphthoquinone Sulfonamide and Sulfonate Ester Derivatives

2022 ◽  
Author(s):  
Paulo Pacheco ◽  
Daniel Gonzaga ◽  
Cláudio Cirne-Santos ◽  
Caroline Barros ◽  
Max Gomes ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Pharmacological Treatment ◽  
Drug Targets ◽  
Chikungunya Virus ◽  
Antiviral Drug ◽  
Sulfonate Group ◽  
In Silico Studies ◽  
Virucidal Effect ◽  
Toxic Potential ◽  
Sulfonate Ester

Chikungunya virus (CHIKV) is a re-emerging disease caused by an alphavirus of the Togaviridae family. Since its first description in 1952, the disease has spread worldwide, affecting populations in both tropical and temperate countries. To date, there is no licensed vaccine or specific pharmacological treatment. Therefore, there is an increasing urgency in developing new antiviral drugs capable of specifically inhibiting viral replication. In the present work, we report the synthesis and antiviral activity evaluation of nineteen naphthoquinone derivatives, containing a sulfonamide or sulfonate group. Cell viability assays indicated a low toxic potential for all tested compounds and inhibitory assays against CHIKV identified five compounds with potent activity. The compounds were also evaluated for their virucidal potential, and the results demonstrated that compound 11a exhibited a virucidal effect higher than 70% in the treatment with 20 µM. Furthermore, in silico studies were performed to predict the antiviral drug targets.

Impact of Novel Coronavirus (COVID-19) on Pregnant Women: A Review

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Saima Habeeb ◽  
Manju Chugani
Keyword(s):  
Pregnant Women ◽  
Vertical Transmission ◽  
Respiratory Infections ◽  
Age Groups ◽  
Well Being ◽  
Fetal Outcome ◽  
Global Public Health ◽  
Coronavirus Infection ◽  
Novel Coronavirus ◽  
The Impact

: The novel coronavirus infection (COVID‐19) is a global public health emergency.Since its outbreak in Wuhan, China in December 2019, the infection has spread at an alarming rate across the globe and humans have been locked down to their countries, cities and homes. As of now, the virus has affected over 20million people globally and has inflicted over 7 lac deaths. Nevertheless, the recovery rate is improving with each passing day and over 14 million people have recuperated so far. The statistics indicate that nobody is immune to the disease as the virus continues to spread among all age groups; newborns to the elders, and all compartmentsincluding pregnant women. However, pregnant women may be more susceptible to this infection as they are, in general, highly vulnerable to respiratory infections. There is no evidence for vertical transmission of the COVID-19 virus among pregnant women, but an increased prevalence of preterm deliveries. Besides this, the COVID-19 may alter immune response at the maternal-fetal interface and affect the well-being of mothers as well as infants. Unfortunately, there is limited evidence available in the open literature regarding coronavirus infection during pregnancy and it now appears that certain pregnant women have infected during the present 2019-nCoV pandemic. In this short communication, we study the impact of the COVID-19 infection on vertical transmission and fetal outcome among pregnant women.

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