scholarly journals Host Cell and SARS-CoV-2-Associated Molecular Structures and Factors as Potential Therapeutic Targets

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2427
Author(s):  
Jitendra Kumar Chaudhary ◽  
Rohitash Yadav ◽  
Pankaj Kumar Chaudhary ◽  
Anurag Maurya ◽  
Rakesh Roshan ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Clinical Outcome ◽  
Host Cell ◽  
Rna Virus ◽  
Critical Role ◽  
Viral Disease ◽  
Molecular Structures ◽  
Cell Surface Receptor ◽  
Structural Proteins ◽  
Lectin Receptors

Coronavirus disease 19 (COVID-19) is caused by an enveloped, positive-sense, single-stranded RNA virus, referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the realm Riboviria, order Nidovirales, family Coronaviridae, genus Betacoronavirus and the species Severe acute respiratory syndrome-related coronavirus. This viral disease is characterized by a myriad of varying symptoms, such as pyrexia, cough, hemoptysis, dyspnoea, diarrhea, muscle soreness, dysosmia, lymphopenia and dysgeusia amongst others. The virus mainly infects humans, various other mammals, avian species and some other companion livestock. SARS-CoV-2 cellular entry is primarily accomplished by molecular interaction between the virus’s spike (S) protein and the host cell surface receptor, angiotensin-converting enzyme 2 (ACE2), although other host cell-associated receptors/factors, such as neuropilin 1 (NRP-1) and neuropilin 2 (NRP-2), C-type lectin receptors (CLRs), as well as proteases such as TMPRSS2 (transmembrane serine protease 2) and furin, might also play a crucial role in infection, tropism and pathogenesis and clinical outcome. Furthermore, several structural and non-structural proteins of the virus themselves are very critical in determining the clinical outcome following infection. Considering such critical role(s) of the abovementioned host cell receptors, associated proteases/factors and virus structural/non-structural proteins (NSPs), it may be quite prudent to therapeutically target them through a multipronged clinical regimen to combat the disease.

scholarly journals Roles of the Non-Structural Proteins of Influenza A Virus

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 812
Author(s):  
Wenzhuo Hao ◽  
Lingyan Wang ◽  
Shitao Li
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Rna Virus ◽  
Critical Role ◽  
Viral Proteins ◽  
Host Cells ◽  
Structural Proteins ◽  
Host Interactions ◽  
New Findings ◽  
Seasonal Epidemics

Influenza A virus (IAV) is a segmented, negative single-stranded RNA virus that causes seasonal epidemics and has a potential for pandemics. Several viral proteins are not packed in the IAV viral particle and only expressed in the infected host cells. These proteins are named non-structural proteins (NSPs), including NS1, PB1-F2 and PA-X. They play a versatile role in the viral life cycle by modulating viral replication and transcription. More importantly, they also play a critical role in the evasion of the surveillance of host defense and viral pathogenicity by inducing apoptosis, perturbing innate immunity, and exacerbating inflammation. Here, we review the recent advances of these NSPs and how the new findings deepen our understanding of IAV–host interactions and viral pathogenesis.

scholarly journals Genetics of Severe Acute Respiratory Syndrome Coronavirus-2 and Diagnosis of Coronavirus Disease-2019: An Overview

2020 ◽  
Vol 22 (2) ◽  
pp. 236-247
Author(s):  
Anshuman Sewda ◽  
Shiv Dutt Gupta
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Rna Virus ◽  
Infected Individual ◽  
Structural Proteins ◽  
Epidemiological Surveillance ◽  
Host Immune System ◽  
Angiotensin Converting Enzyme 2 ◽  
Containment Measures ◽  
Rapid Tests ◽  
Specific Antigens

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a positive sense, single-stranded RNA virus, responsible for the ‘coronavirus disease-2019’ (COVID-19) pandemic. SARS-CoV-2 belongs to the sarbecovirus (lineage-B) sub-genus within the betacoronavirus genus of the coronaviridae family. SARS-CoV-2 shares similarities with SARS-CoV, which was responsible for the 2003 SARS epidemic. SARS-CoV-2 binds with great affinity to the Angiotensin Converting Enzyme-2 receptors on human cells, and its ~30 kilobases long RNA genome hijacks the host machinery and compromises the host immune system with the help of accessory proteins, such as non-structural proteins, resulting in a widespread infection. The spike protein is responsible for the contagious nature of SARS-CoV-2 and, together with the nucleocapsid protein, elicits the host inflammatory response. Several real-time reverse transcriptase polymerase chain reaction (rRT-PCR) tests have been developed to confirm SARS-CoV-2 infection in suspected cases of COVID-19. Furthermore, rapid tests based on SARS-CoV-2-specific antigens and antibodies have been developed to conduct epidemiological surveillance of the hotspot regions that are worst affected by the COVID-19 pandemic. Until effective measures to prevent the occurrence or spread of COVID-19 pandemic are developed, containment measures are being taken, such as isolation of confirmed COVID-19 patients, quarantine of individuals who may have come in contact with a SARS-CoV-2 infected individual, community-wide social distancing, state/nation-wide lockdown, etc. Several vaccines and drugs are being tested that could target the viral structural proteins, non-structural proteins or associated SARS-CoV-2 sub-genomic RNA regions.

scholarly journals ACE2 Homo-dimerization, Human Genomic variants and Interaction of Host Proteins Explain High Population Specific Differences in Outcomes of COVID19

2020 ◽  
Author(s):  
Swarkar Sharma ◽  
Inderpal Singh ◽  
Shazia Haider ◽  
Md. Zubbair Malik ◽  
Kalaiarasan Ponnusamy ◽  
...  
Keyword(s):  
Host Cell ◽  
Virus Disease ◽  
Rna Virus ◽  
Critical Role ◽  
Host Cells ◽  
Therapeutic Interventions ◽  
World Health ◽  
Structural Variations ◽  
S Protein ◽  
Differential Outcomes

ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive single-stranded RNA virus that causes a highly contagious Corona Virus Disease (COVID19). Entry of SARS-CoV-2 in human cells depends on binding of the viral spike (S) proteins to cellular receptor Angiotensin-converting enzyme 2 (ACE2) and on S-protein priming by host cell serine protease TMPRSS2. Recently, COVID19 has been declared pandemic by World Health Organization (WHO) yet high differences in disease outcomes across countries have been seen. We provide evidences to explain these population-level differences. One of the key factors of entry of the virus in host cells presumably is because of differential interaction of viral proteins with host cell proteins due to different genetic backgrounds. Based on our findings, we conclude that a higher expression of ACE2 is facilitated by natural variations, acting as Expression quantitative trait loci (eQTLs), with different frequencies in different populations. We suggest that high expression of ACE2 results in homo-dimerization, proving disadvantageous for TMPRSS2 mediated cleavage of ACE2; whereas, the monomeric ACE2 has higher preferential binding with SARS-CoV-2 S-Protein vis-a-vis its dimerized counterpart. Further, eQTLs in TMPRSS2 and natural structural variations in the gene may also result in differential outcomes towards priming of viral S-protein, a critical step for entry of the Virus in host cells. In addition, we suggest that several key host genes, like SLC6A19, ADAM17, RPS6, HNRNPA1, SUMO1, NACA, BTF3 and some other proteases as Cathepsins, might have a critical role. To conclude, understanding population specific differences in these genes may help in developing appropriate management strategies for COVID19 with better therapeutic interventions.

Plasma therapy a possible hope to fight against COVID-19

2020 ◽  
Author(s):  
Ravikant Piyush ◽  
Aroni Chatterjee ◽  
Shashikant Ray
Keyword(s):  
Middle East ◽  
Severe Acute Respiratory Syndrome ◽  
Viral Disease ◽  
Plasma Therapy ◽  
Therapeutic Drugs ◽  
Wild Fire ◽  
The World ◽  
Short Span ◽  
Game Changer

The world is currently going through a disastrous event and a catastrophic upheaval caused by the coronavirus disease 2019 (COVID-19). The pandemic has resulted in loss of more than 150000 deaths across the globe. Originating from China and spreading across all continents within a short span of time, it has become a matter of international emergency. Different agencies are adopting diverse approaches to stop and spread of this viral disease but still now nothing confirmatory has come up. Due to lack of vaccines and proper therapeutic drugs, the disease is still spreading like wild fire without control. An Old but very promising method- the convalescent plasma therapy could be the key therapy to stop this pandemic. This method has already proven its mettle on several occasions previously and has been found to be effective in curing the pandemics induced by Ebola, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the same group of β-Coronavirus that has resulted in the above diseases. Therefore, the role of plasma therapy is being explored for treatment of this disease. In this review, we have mainly focused on the role of convalescent plasma therapy and why its use should be promoted in fight against COVID-19, as it could turn out to be a game changer.

Recent Advances in the Function of the 67 kDa Laminin Receptor and its Targeting for Personalized Therapy in Cancer

2017 ◽  
Vol 23 (32) ◽  
pp. 4745-4757 ◽  
Author(s):  
Ada Pesapane ◽  
Pia Ragno ◽  
Carmine Selleri ◽  
Nunzia Montuori
Keyword(s):  
Cell Adhesion ◽  
Cancer Progression ◽  
Ribosome Biogenesis ◽  
Critical Role ◽  
Protein Translation ◽  
Basement Membranes ◽  
Laminin Receptor ◽  
Cell Surface Receptor ◽  
Future Application ◽  
Neoplastic Cells

The 67 kDa high affinity laminin receptor (67LR) is a non-integrin cell surface receptor for laminin, the major component of basement membranes. Interactions between 67LR and laminin play a major role in mediating cell adhesion, migration, proliferation and survival. 67LR derives from homo- or hetero-dimerization of a 37 kDa cytosolic precursor (37LRP), most probably by fatty acid acylation. Interestingly, 37LRP, also called p40 or OFA/iLR (oncofetal antigen/immature laminin receptor), is a multifunctional protein with a dual activity in the cytoplasm and in the nucleus. In the cytoplasm, 37LRP it is associated with the 40S subunit of ribosome, playing a critical role in protein translation and ribosome biogenesis while in the nucleus it is tightly associated with nuclear structures, and bound to components of the cytoskeleton, such as tubulin and actin. 67LR is mainly localized in the cell membrane, concentrated in lipid rafts. Acting as a receptor for laminin is not the only function of 67LR; indeed, it also acts as a receptor for viruses, bacteria and prions. 67LR expression is increased in neoplastic cells and correlates with an enhanced invasive and metastatic potential. The primary function of 67LR in cancer is to promote tumor cell adhesion to basement membranes, the first step in the invasion-metastasis cascade. Thus, 67LR is overexpressed in neoplastic cells as compared to their normal counterparts and its overexpression is considered a molecular marker of metastatic aggressiveness in cancer of many tissues, including breast, lung, ovary, prostate, stomach, thyroid and also in leukemia and lymphoma. Thus, inhibiting 67LR binding to laminin could be a feasible approach to block cancer progression. Here, we review the current understanding of the structure and function of this molecule, highlighting its role in cancer invasion and metastasis and reviewing the various therapeutic options targeting this receptor that could have a promising future application.

scholarly journals Protease Inhibitors as Antiviral Agents

1998 ◽  
Vol 11 (4) ◽  
pp. 614-627 ◽  
Author(s):  
A. K. Patick ◽  
K. E. Potts
Keyword(s):  
Protease Inhibitors ◽  
Viral Infections ◽  
Critical Role ◽  
Antiviral Agents ◽  
Antiviral Agent ◽  
Structural Proteins ◽  
Viral Protease ◽  
Virus Particles ◽  
Viral Proteases ◽  
Viral Polyprotein

SUMMARY Currently, there are a number of approved antiviral agents for use in the treatment of viral infections. However, many instances exist in which the use of a second antiviral agent would be beneficial because it would allow the option of either an alternative or a combination therapeutic approach. Accordingly, virus-encoded proteases have emerged as new targets for antiviral intervention. Molecular studies have indicated that viral proteases play a critical role in the life cycle of many viruses by effecting the cleavage of high-molecular-weight viral polyprotein precursors to yield functional products or by catalyzing the processing of the structural proteins necessary for assembly and morphogenesis of virus particles. This review summarizes some of the important general features of virus-encoded proteases and highlights new advances and/or specific challenges that are associated with the research and development of viral protease inhibitors. Specifically, the viral proteases encoded by the herpesvirus, retrovirus, hepatitis C virus, and human rhinovirus families are discussed.

scholarly journals Immunoinformatics-guided design of a multi-epitope vaccine based on the structural proteins of severe acute respiratory syndrome coronavirus 2

RSC Advances ◽  
2021 ◽  
Vol 11 (29) ◽  
pp. 18103-18121
Author(s):  
Ahmad J. Obaidullah ◽  
Mohammed M. Alanazi ◽  
Nawaf A. Alsaif ◽  
Hussam Albassam ◽  
Abdulrahman A. Almehizia ◽  
...  
Keyword(s):  
Tract Infection ◽  
Severe Acute Respiratory Syndrome ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Structural Proteins ◽  
Epitope Vaccine

COVID-19 is caused by SARS-CoV-2, resulting in a contagious respiratory tract infection. For designing a multi-epitope vaccine, we utilized the four structural proteins from the SARS-CoV-2 by using bioinformatics and immunoinformatics analysis.

scholarly journals Why Does SARS-CoV-2 Infection Induce Autoantibody Production?

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 380
Author(s):  
Ales Macela ◽  
Klara Kubelkova
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Host Cell ◽  
Critical Role ◽  
Cell Interaction ◽  
Immune Recognition ◽  
Autoantibody Production ◽  
Host Cell Interaction ◽  
Primary Virus

SARS-CoV-2 infection induces the production of autoantibodies, which is significantly associated with complications during hospitalization and a more severe prognosis in COVID-19 patients. Such a response of the patient’s immune system may reflect (1) the dysregulation of the immune response or (2) it may be an attempt to regulate itself in situations where the non-infectious self poses a greater threat than the infectious non-self. Of significance may be the primary virus-host cell interaction where the surface-bound ACE2 ectoenzyme plays a critical role. Here, we present a brief analysis of recent findings concerning the immune recognition of SARS-CoV-2, which, we believe, favors the second possibility as the underlying reason for the production of autoantibodies during COVID-19.

scholarly journals Essential role of IPS-1 in innate immune responses against RNA viruses

2006 ◽  
Vol 203 (7) ◽  
pp. 1795-1803 ◽  
Author(s):  
Himanshu Kumar ◽  
Taro Kawai ◽  
Hiroki Kato ◽  
Shintaro Sato ◽  
Ken Takahashi ◽  
...  
Keyword(s):  
Rna Viruses ◽  
Rna Virus ◽  
Critical Role ◽  
Nuclear Factor Κb ◽  
Type I ◽  
Innate Immune Responses ◽  
Antiviral Responses ◽  
Deficient Mice

IFN-β promoter stimulator (IPS)-1 was recently identified as an adapter for retinoic acid–inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (Mda5), which recognize distinct RNA viruses. Here we show the critical role of IPS-1 in antiviral responses in vivo. IPS-1–deficient mice showed severe defects in both RIG-I– and Mda5-mediated induction of type I interferon and inflammatory cytokines and were susceptible to RNA virus infection. RNA virus–induced interferon regulatory factor-3 and nuclear factor κB activation was also impaired in IPS-1–deficient cells. IPS-1, however, was not essential for the responses to either DNA virus or double-stranded B-DNA. Thus, IPS-1 is the sole adapter in both RIG-I and Mda5 signaling that mediates effective responses against a variety of RNA viruses.

scholarly journals Modulation of Autophagy by SARS-CoV-2: A Potential Threat for Cardiovascular System

2020 ◽  
Vol 11 ◽  
Author(s):  
Puneet Kaur Randhawa ◽  
Kaylyn Scanlon ◽  
Jay Rappaport ◽  
Manish K. Gupta
Keyword(s):  
Host Cell ◽  
Rna Virus ◽  
Clinical Manifestations ◽  
Cardiovascular Complications ◽  
Extracellular Proteases ◽  
Potential Threat ◽  
Surface Receptors ◽  
Drug Candidates ◽  
A Genome ◽  
Number Of Patients

Recently, we have witnessed an unprecedented increase in the number of patients suffering from respiratory tract illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 virus is a single-stranded positive-sense RNA virus with a genome size of ~29.9 kb. It is believed that the viral spike (S) protein attaches to angiotensin converting enzyme 2 cell surface receptors and, eventually, the virus gains access into the host cell with the help of intracellular/extracellular proteases or by the endosomal pathway. Once, the virus enters the host cell, it can either be degraded via autophagy or evade autophagic degradation and replicate using the virus encoded RNA dependent RNA polymerase. The virus is highly contagious and can impair the respiratory system of the host causing dyspnea, cough, fever, and tightness in the chest. This disease is also characterized by an abrupt upsurge in the levels of proinflammatory/inflammatory cytokines and chemotactic factors in a process known as cytokine storm. Certain reports have suggested that COVID-19 infection can aggravate cardiovascular complications, in fact, the individuals with underlying co-morbidities are more prone to the disease. In this review, we shall discuss the pathogenesis, clinical manifestations, potential drug candidates, the interaction between virus and autophagy, and the role of coronavirus in exaggerating cardiovascular complications.

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