Possible Targets and Therapies of SARS-CoV-2 Infection

2020 ◽  
Vol 20 (18) ◽  
pp. 1900-1907
Author(s):  
Kasturi Sarkar ◽  
Parames C. Sil ◽  
Seyed Fazel Nabavi ◽  
Ioana Berindan-Neagoe ◽  
Cosmin Andrei Cismaru ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Viral Replication ◽  
Viral Infection ◽  
Human Activity ◽  
Viral Proteins ◽  
Therapeutic Agents ◽  
Effective Control ◽  
Human Society ◽  
Global Spread ◽  
Repurposed Drugs

The global spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes COVID-19 has become a source of grave medical and socioeconomic concern to human society. Since its first appearance in the Wuhan region of China in December 2019, the most effective measures of managing the spread of SARS-CoV-2 infection have been social distancing and lockdown of human activity; the level of which has not been seen in our generations. Effective control of the viral infection and COVID-19 will ultimately depend on the development of either a vaccine or therapeutic agents. This article highlights the progresses made so far in these strategies by assessing key targets associated with the viral replication cycle. The key viral proteins and enzymes that could be targeted by new and repurposed drugs are discussed.

scholarly journals Methyltransferase-like 3 modulates severe acute respiratory syndrome coronavirus-2 RNA N6-methyladenosine modification and replication

2020 ◽  
Author(s):  
Xueyan Zhang ◽  
Haojie Hao ◽  
Li Ma ◽  
Yecheng Zhang ◽  
Xiao Hu ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Viral Replication ◽  
Viral Proteins ◽  
Rna Modification ◽  
Hairpin Rna ◽  
Unknown Mechanism ◽  
Public Crisis ◽  
Rna Immunoprecipitation ◽  
Short Hairpin ◽  
Plasmid Transfection

ABSTRACTThe coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an ongoing global public crisis. Although viral RNA modification has been reported based on the transcriptome architecture, the types and functions of RNA modification are still unknown. In this study, we evaluated the roles of RNA N6-methyladenosine (m6A) modification in SARS-CoV-2. Our methylated RNA immunoprecipitation sequencing (MeRIP-Seq) analysis showed that SARS-CoV-2 RNA contained m6A modification. Moreover, SARS-CoV-2 infection not only increased the expression of methyltransferase-like 3 (METTL3) but also altered its distribution. Modification of METTL3 expression by short hairpin RNA or plasmid transfection for knockdown or overexpression, respectively, affected viral replication. Furthermore, the viral key protein RdRp interacted with METTL3, and METTL3 was distributed in both the nucleus and cytoplasm in the presence of RdRp. RdRp appeared to modulate the sumoylation and ubiquitination of METTL3 via an unknown mechanism. Taken together, our findings demonstrated that the host m6A modification complex interacted with viral proteins to modulate SARS-CoV-2 replication.

scholarly journals Host MicroRNA miR-197 Plays a Negative Regulatory Role in the Enterovirus 71 Infectious Cycle by Targeting the RAN Protein

2015 ◽  
Vol 90 (3) ◽  
pp. 1424-1438 ◽  
Author(s):  
Wen-Fang Tang ◽  
Ru-Ting Huang ◽  
Kun-Yi Chien ◽  
Jo-Yun Huang ◽  
Kean-Seng Lau ◽  
...  
Keyword(s):  
Viral Replication ◽  
Viral Infection ◽  
Target Genes ◽  
Nuclear Transport ◽  
Enterovirus 71 ◽  
Viral Proteins ◽  
Translation Initiation Factor ◽  
Host Protein ◽  
Dependent Manner ◽  
Host Proteins

ABSTRACTEnterovirus 71 (EV71), a member ofPicornaviridae, is associated with severe central nervous system complications. In this study, we identified a cellular microRNA (miRNA), miR-197, whose expression was downregulated by viral infection in a time-dependent manner. In miR-197 mimic-transfected cells, EV71 replication was inhibited, whereas the internal ribosome entry site (IRES) activity was decreased in EV71 strains with or without predicted miR-197 target sites, indicating that miR-197 targets host proteins to modulate viral replication. We thus used a quantitative proteomics approach, aided by the TargetScan algorithm, to identify putative target genes of miR-197. Among them, RAN was selected and validated as a genuine target in a 3′ untranslated region (UTR) reporter assay. Reduced production of RAN by RNA interference markedly reduced the synthesis of EV71-encoded viral proteins and virus titers. Furthermore, reintroduction of nondegradable RAN into these knockdown cells rescued viral protein synthesis. miR-197 levels were modulated by EV71 to maintain RAN mRNA translatability at late times postinfection since we demonstrated that cap-independent translation exerted by its intrinsic IRES activity was occurring at times when translation attenuation was induced by EV71. EV71-induced downregulation of miR-197 expression increased the expression of RAN, which supported the nuclear transport of the essential viral proteins 3D/3CD and host protein hnRNP K for viral replication. Our data suggest that downregulation of cellular miRNAs may constitute a newly identified mechanism that sustains the expression of host proteins to facilitate viral replication.IMPORTANCEEnterovirus 71 (EV71) is a picornavirus with a positive-sense single-stranded RNA that globally inhibits the cellular translational system, mainly by cleaving cellular eukaryotic translation initiation factor 4G (eIF4G) and poly(A)-binding protein (PABP), which inhibits the association of the ribosome with the host capped mRNA. We used a microRNA (miRNA) microarray chip to identify the host miRNA 197 (miR-197) that was downregulated by EV71. We also used quantitative mass spectrometry and a target site prediction tool to identify the miR-197 target genes. During viral infection, the expression of the target protein RAN was upregulated considerably, and there was a parallel downregulation of miR-197. The nuclear transport of viral 3D/3CD protein and of the host proteins involved in viral replication proceeded in an RAN-dependent manner. We have identified a new mechanism in picornavirus through which EV71-induced cellular miRNA downregulation can regulate host protein levels to facilitate viral replication.

scholarly journals Enteric Fever Diagnosis: Current Challenges and Future Directions

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 410
Author(s):  
Durga P. Neupane ◽  
Hari P. Dulal ◽  
Jeongmin Song
Keyword(s):  
Diagnostic Tests ◽  
Enteric Fever ◽  
Asymptomatic Carrier ◽  
Diagnostic Methods ◽  
Effective Control ◽  
Future Directions ◽  
Clinical Presentations ◽  
Global Spread ◽  
Life Threatening ◽  
Pros And Cons

Enteric fever is a life-threatening systemic febrile disease caused by Salmonella enterica serovars Typhi and Paratyphi (S. Typhi and S. Paratyphi). Unfortunately, the burden of the disease remains high primarily due to the global spread of various drug-resistant Salmonella strains despite continuous advancement in the field. An accurate diagnosis is critical for effective control of the disease. However, enteric fever diagnosis based on clinical presentations is challenging due to overlapping symptoms with other febrile illnesses that are also prevalent in endemic areas. Current laboratory tests display suboptimal sensitivity and specificity, and no diagnostic methods are available for identifying asymptomatic carriers. Several research programs have employed systemic approaches to identify more specific biomarkers for early detection and asymptomatic carrier detection. This review discusses the pros and cons of currently available diagnostic tests for enteric fever, the advancement of research toward improved diagnostic tests, and the challenges of discovering new ideal biomarkers and tests.

scholarly journals Identification of Anti-Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Oxysterol Derivatives In Vitro

2021 ◽  
Vol 22 (6) ◽  
pp. 3163
Author(s):  
Hirofumi Ohashi ◽  
Feng Wang ◽  
Frank Stappenbeck ◽  
Kana Tsuchimoto ◽  
Chisa Kobayashi ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Viral Replication ◽  
Cultured Cells ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Membrane Vesicles ◽  
Drug Candidates ◽  
Increased Risk ◽  
Derivatives Of

The development of effective antiviral drugs targeting the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is urgently needed to combat the coronavirus disease 2019 (COVID-19). We have previously studied the use of semi-synthetic derivatives of oxysterols, oxidized derivatives of cholesterol as drug candidates for the inhibition of cancer, fibrosis, and bone regeneration. In this study, we screened a panel of naturally occurring and semi-synthetic oxysterols for anti-SARS-CoV-2 activity using a cell culture infection assay. We show that the natural oxysterols, 7-ketocholesterol, 22(R)-hydroxycholesterol, 24(S)-hydroxycholesterol, and 27-hydroxycholesterol, substantially inhibited SARS-CoV-2 propagation in cultured cells. Among semi-synthetic oxysterols, Oxy210 and Oxy232 displayed more robust anti-SARS-CoV-2 activities, reducing viral replication more than 90% at 10 μM and 99% at 15 μM, respectively. When orally administered in mice, peak plasma concentrations of Oxy210 fell into a therapeutically relevant range (19 μM), based on the dose-dependent curve for antiviral activity in our cell-based assay. Mechanistic studies suggest that Oxy210 reduced replication of SARS-CoV-2 by disrupting the formation of double-membrane vesicles (DMVs); intracellular membrane compartments associated with viral replication. Our study warrants further evaluation of Oxy210 and Oxy232 as a safe and reliable oral medication, which could help protect vulnerable populations with increased risk of developing COVID-19.

scholarly journals Essential Role of Quantum Science and Nanoscience in Antiviral Strategies

2021 ◽  
Author(s):  
Mina Zare ◽  
Mika Sillanpää ◽  
Seeram Ramakrishna
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Viral Infection ◽  
Essential Role ◽  
Quantum Science

The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) caused the pandemic COVID-19 disease since December 2019 highlights the importance of developing efficient antiviral strategies to prevent and treat viral infection. Virus...

SARS-CoV-2: Molecular biology and therapeutic target.

Coronaviruses ◽  
2021 ◽  
Vol 02 ◽  
Author(s):  
Vivek Pandey ◽  
Ankita Pathak ◽  
Mohammad Shahar Yar ◽  
Yuba Raj Pokharel
Keyword(s):  
Viral Genome ◽  
Vaccine Development ◽  
Viral Proteins ◽  
Current Review ◽  
The World ◽  
Spanish Flu ◽  
Repurposed Drugs ◽  
Key Features ◽  
Economic Infrastructure ◽  
Viral Outbreak

: A century after the outbreak of the Spanish flu, the world is suffering with another pandemic on because of the coronavirus. The virus took a toll of more than millions of lives worldwide and still continues to affect the health and socio-economic infrastructure all over the world. The study explores the epidemiology, etiology and transmission of the virus and its phylogenetic relationship with SARS and MERS coronavirus responsible for 2002 and 2012 viral outbreak. Highlights about the key features of the viral genome and essential viral proteins responsible for viral life cycle, evading host immune response, and viral immunopathology with therapeutics from “Recovery” and “Solidarity” trials, are major concern of the current review. The review culminated with a discussion on different classes of front-runners vaccines and their efficacy. An overall understanding of essential viral proteins and their role in pathogenesis, repurposed drugs and vaccine development is the rationale of the present review.

scholarly journals Network-Guided Discovery of Influenza Virus Replication Host Factors

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Emily E. Ackerman ◽  
Eiryo Kawakami ◽  
Manami Katoh ◽  
Tokiko Watanabe ◽  
Shinji Watanabe ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Viral Replication ◽  
Virus Replication ◽  
Drug Targets ◽  
Antiviral Drug ◽  
Viral Proteins ◽  
Host Factors ◽  
Ppi Network ◽  
Host Proteins ◽  
Influenza Virus Replication

ABSTRACTThe positions of host factors required for viral replication within a human protein-protein interaction (PPI) network can be exploited to identify drug targets that are robust to drug-mediated selective pressure. Host factors can physically interact with viral proteins, be a component of virus-regulated pathways (where proteins do not interact with viral proteins), or be required for viral replication but unregulated by viruses. Here, we demonstrate a method of combining human PPI networks with virus-host PPI data to improve antiviral drug discovery for influenza viruses by identifying target host proteins. Analysis shows that influenza virus proteins physically interact with host proteins in network positions significant for information flow, even after the removal of known abundance-degree bias within PPI data. We have isolated a subnetwork of the human PPI network that connects virus-interacting host proteins to host factors that are important for influenza virus replication without physically interacting with viral proteins. The subnetwork is enriched for signaling and immune processes distinct from those associated with virus-interacting proteins. Selecting proteins based on subnetwork topology, we performed an siRNA screen to determine whether the subnetwork was enriched for virus replication host factors and whether network position within the subnetwork offers an advantage in prioritization of drug targets to control influenza virus replication. We found that the subnetwork is highly enriched for target host proteins—more so than the set of host factors that physically interact with viral proteins. Our findings demonstrate that network positions are a powerful predictor to guide antiviral drug candidate prioritization.IMPORTANCEIntegrating virus-host interactions with host protein-protein interactions, we have created a method using these established network practices to identify host factors (i.e., proteins) that are likely candidates for antiviral drug targeting. We demonstrate that interaction cascades between host proteins that directly interact with viral proteins and host factors that are important to influenza virus replication are enriched for signaling and immune processes. Additionally, we show that host proteins that interact with viral proteins are in network locations of power. Finally, we demonstrate a new network methodology to predict novel host factors and validate predictions with an siRNA screen. Our results show that integrating virus-host proteins interactions is useful in the identification of antiviral drug target candidates.

scholarly journals Neurological Manifestations of COVID-19 patients: An Updated Review and Observations of COVID Patients in the National Institute of Neurosciences and Hospital, Dhaka, Bangladesh

2020 ◽  
pp. 122-132
Author(s):  
Mohammad Enayet Hussain ◽  
Md Azharul Hoque ◽  
Md Badrul Alam ◽  
Md Abdullah Yusuf ◽  
Rajib Nayan Chowdhury ◽  
...  
Keyword(s):  
Nervous System ◽  
Severe Acute Respiratory Syndrome ◽  
Viral Infection ◽  
Clinical Manifestation ◽  
Early Experience ◽  
Neurological Manifestations ◽  
Recent Outbreak ◽  
Near Future

Involvement of the nervous system after viral infection is common. Certain viruses show neurotropism. Recent outbreak of severe acute respiratory syndrome CoV 2 (SARSCov- 2) virus has also exhibited neurotropic properties with various neurological manifestations. The pathophysiology of their neurotropism is not yet clearly known. The details of pathophysiology, clinical manifestation and management are expected to be explored in the near future. Here we review the Neurological manifestations of COVID-19 and the early experience in the National Institute of Neurosciences and Hospital. J Bangladesh Coll Phys Surg 2020; 38(0): 122-132

scholarly journals Secretome Screening Reveals Fibroblast Growth Factors as Novel Inhibitors of Viral Replication

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Saskia D. van Asten ◽  
Matthijs Raaben ◽  
Benjamin Nota ◽  
Robbert M. Spaapen
Keyword(s):  
Growth Factor ◽  
Viral Replication ◽  
Viral Infection ◽  
Fibroblast Growth Factor ◽  
Oncolytic Virus ◽  
Human Cells ◽  
Secreted Proteins ◽  
Type I ◽  
Fibroblast Growth ◽  
Vesicular Stomatitis

ABSTRACT Cellular antiviral programs can efficiently inhibit viral infection. These programs are often initiated through signaling cascades induced by secreted proteins, such as type I interferons, interleukin-6 (IL-6), or tumor necrosis factor alpha (TNF-α). In the present study, we generated an arrayed library of 756 human secreted proteins to perform a secretome screen focused on the discovery of novel modulators of viral entry and/or replication. The individual secreted proteins were tested for the capacity to inhibit infection by two replication-competent recombinant vesicular stomatitis viruses (VSVs) with distinct glycoproteins utilizing different entry pathways. Fibroblast growth factor 16 (FGF16) was identified and confirmed as the most prominent novel inhibitor of both VSVs and therefore of viral replication, not entry. Importantly, an antiviral interferon signature was completely absent in FGF16-treated cells. Nevertheless, the antiviral effect of FGF16 is broad, as it was evident on multiple cell types and also on infection by coxsackievirus. In addition, other members of the FGF family also inhibited viral infection. Thus, our unbiased secretome screen revealed a novel protein family capable of inducing a cellular antiviral state. This previously unappreciated role of the FGF family may have implications for the development of new antivirals and the efficacy of oncolytic virus therapy. IMPORTANCE Viruses infect human cells in order to replicate, while human cells aim to resist infection. Several cellular antiviral programs have therefore evolved to resist infection. Knowledge of these programs is essential for the design of antiviral therapeutics in the future. The induction of antiviral programs is often initiated by secreted proteins, such as interferons. We hypothesized that other secreted proteins may also promote resistance to viral infection. Thus, we tested 756 human secreted proteins for the capacity to inhibit two pseudotypes of vesicular stomatitis virus (VSV). In this secretome screen on viral infection, we identified fibroblast growth factor 16 (FGF16) as a novel antiviral against multiple VSV pseudotypes as well as coxsackievirus. Subsequent testing of other FGF family members revealed that FGF signaling generally inhibits viral infection. This finding may lead to the development of new antivirals and may also be applicable for enhancing oncolytic virus therapy.

Coronavirus and Fingerprint Technology

2021 ◽  
Vol 13 (4) ◽  
pp. 1-16
Author(s):  
Gabriel B. Iwasokun
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Viral Infection ◽  
Virus Disease ◽  
High Rate ◽  
Corona Virus ◽  
The World ◽  
Almost All

The corona virus disease, otherwise known as COVID-19, is an extremely communicable and pathogenic viral infection caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), which emerged in Wuhan, China in December 2019 and has spread to almost all the countries in the world. The transmission of the virus is through touching of the nose, eyes, or mouth by a finger that has been contaminated through droplets on a surface when a carrier sneezes or coughs. Since the existing fingerprint devices are predominantly contact based, it implies that they can aid in the transmission of the virus. This paper discusses the application of fingerprint devices in notable places with high rate of COVID-19 infection as well as the threats to fingerprint technologies and the countermeasures. The need to change focus and orientation towards contactless biometric technologies as sure solution to the fear and animosity expressed towards contact-based fingerprint technology is also expatiated.

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