Spike protein of SARS-COV-2 as a potential target for phytochemical constituents: A literature review

SARS-CoV-2 belongs to well-known SARS Coronaviridae family. One of the main structural proteins of SARS-CoV-2 is the spike protein that is present around the surface of a viral cell and plays an essential role in viral attachment, fusion and invasion in host cell. Once a virus invades a cell, it replicates and infects other cells. The fundamental role of spike protein in the progression of viral infection has led to an increased interest in exploring agents that target the viral spike protein for effective control of CoVID-19. The related data from published articles reviewed and numerous phytochemicals that reportedly target the spike proteins of coronaviruses by computational studies briefly discussed. These active constituents possess the potential to develop as therapeutic and antiviral agents against SARS-CoV-2.

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Multidrug treatment with nelfinavir and cepharanthine against COVID-19

10.1101/2020.04.14.039925 ◽

2020 ◽

Cited By ~ 15

Author(s):

Hirofumi Ohashi ◽

Koichi Watashi ◽

Wakana Saso ◽

Kaho Shionoya ◽

Shoya Iwanami ◽

...

Keyword(s):

Combined Treatment ◽

Antiviral Agents ◽

Hiv Protease ◽

Viral Attachment ◽

Main Protease ◽

Culture Model ◽

Progression Of Disease ◽

A Cell ◽

Approved Drugs

SummaryAntiviral treatments targeting the emerging coronavirus disease 2019 (COVID-19) are urgently required. We screened a panel of already-approved drugs in a cell culture model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and identified two new antiviral agents: the HIV protease inhibitor Nelfinavir and the anti-inflammatory drug Cepharanthine. In silico modeling shows Nelfinavir binds the SARS-CoV-2 main protease consistent with its inhibition of viral replication, whilst Cepharanthine inhibits viral attachment and entry into cells. Consistent with their different modes of action, in vitro assays highlight a synergistic effect of this combined treatment to limit SARS-CoV-2 proliferation. Mathematical modeling in vitro antiviral activity coupled with the known pharmacokinetics for these drugs predicts that Nelfinavir will facilitate viral clearance. Combining Nelfinavir/Cepharanthine enhanced their predicted efficacy to control viral proliferation, to ameliorate both the progression of disease and risk of transmission. In summary, this study identifies a new multidrug combination treatment for COVID-19.

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Replicase Genes of Murine Coronavirus Strains A59 and JHM Are Interchangeable: Differences in Pathogenesis Map to the 3′ One-Third of the Genome

Journal of Virology ◽

10.1128/jvi.01944-06 ◽

2006 ◽

Vol 81 (2) ◽

pp. 1022-1026 ◽

Cited By ~ 7

Author(s):

Sonia Navas-Martin ◽

Maarten Brom ◽

Ming-Ming Chua ◽

Richard Watson ◽

Zhaozhu Qiu ◽

...

Keyword(s):

Acute Infection ◽

Spike Protein ◽

Structural Proteins ◽

Replicase Gene ◽

Recombinant Viruses ◽

Murine Coronavirus

ABSTRACT The important roles of the spike protein and other structural proteins in murine coronavirus (MHV) pathogenesis have been demonstrated; however, the role of the replicase gene remains unexplored. We assessed the influence of the replicase genes of the highly neurovirulent MHV-JHM strain and the hepatotropic and mildly neurovirulent A59 strain in acute infection of the mouse. Analysis of chimeric A59/JHM recombinant viruses indicates that the replicase genes are interchangeable and that it is the 3′ end of the genome, encoding the structural proteins, rather than the replicase gene, that determines the pathogenic properties of these chimeras.

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Analysis of the role of ICAM-3 as a costimulatory molecule through a cell model: CAMY-1 and CAMY-2 (two CD50-negative Jurkat-T cell clones)

Immunology Letters ◽

10.1016/s0165-2478(97)87030-7 ◽

1997 ◽

Vol 56 (1-3) ◽

pp. 52

Author(s):

C Vilardell

Keyword(s):

T Cell ◽

Cell Model ◽

Costimulatory Molecule ◽

T Cell Clones ◽

Cell Clones ◽

Jurkat T Cell ◽

A Cell

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SARS-COV2 virus and Coronavirus disease (COVID-19)

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11ispl1.3401 ◽

2020 ◽

Vol 11 (SPL1) ◽

pp. 977-982

Author(s):

Mohamed J. Saadh ◽

Bashar Haj Rashid M ◽

Roa’a Matar ◽

Sajeda Riyad Aldibs ◽

Hala Sbaih ◽

...

Keyword(s):

Close Contact ◽

Antiviral Agents ◽

Health Concern ◽

The Novel ◽

Global Public Health ◽

Fatal Disease ◽

Mild Disease ◽

Life Threatening ◽

Novel Coronavirus

SARS-COV2 virus causes Coronavirus disease (COVID-19) and represents the causative agent of a potentially fatal disease that is of great global public health concern. The novel coronavirus (2019) was discovered in 2019 in Wuhan, the market of the wet animal, China with viral pneumonia cases and is life-threatening. Today, WHO announces COVID-19 outbreak as a pandemic. COVID-19 is likely to be zoonotic. It is transmitted from bats as intermediary animals to human. Also, the virus is transmitted from human to human who is in close contact with others. The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is nearly supportive; the role of antiviral agents is yet to be established. The SARS-COV2 virus spreads faster than its two ancestors, the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. In this article, we aimed to summarize the transmission, symptoms, pathogenesis, diagnosis, treatment, and vaccine to control the spread of this fatal disease.

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Isolation of Natural Compounds from Syzygium densiflorum Fruits and Exploring its Chemical Property, Therapeutic Role in Diabetic Management

The Natural Products Journal ◽

10.2174/2210315508666180622113414 ◽

2020 ◽

Vol 10 (2) ◽

pp. 168-176

Author(s):

Krishnasamy Gopinath ◽

Nagarajan Subbiah ◽

Muthusamy Karthikeyan

Keyword(s):

Density Functional ◽

Chemical Reactivity ◽

Natural Compounds ◽

Structure Activity Relationship ◽

Activity Relationship ◽

Computational Studies ◽

Therapeutic Role ◽

Relationship Analysis ◽

Structure Activity

Background: Syzygium densiflorum Wall. ex Wight & Arn (Myrtaceae) has been traditionally used by the local tribes of the Nilgiris, Tamil Nadu, India, for the treatment of diabetes. Objective: This study aimed to isolate the major phytoconstituents from the S. densiflorum fruits and to perform computational studies for chemical reactivity and biological activity of the isolated compound. Materials and Methods: Two different compounds were isolated from ethanolic extract of S. densiflorum fruits and purified using HPLC. The structures of the compounds were elucidated on the basis of their 1H NMR, 13C NMR, 1H-1H COSY, HMBC, HRESIMS, and FT-IR data. Further, the chemical reactivity of the compounds was analyzed by density functional theory calculations and its therapeutic role in diabetic management was examined by comparing the structure of isolated compounds with previously reported bioactive compounds. Results: Of the two compounds ((6,6 & 1-kestopentaose (1) and 6-(hydroxymethyl)-3-[3,4,5- trihydroxy- 6-[(3,4,5-trihydroxyoxan-2-yl)oxymethyl]oxan-2-yl]oxyoxane-2,4,5-triol)(2)). β-glucosidase, β-galactosidase, α-glucosidase and β-amylase inhibition activity of the compounds were predicted by structure activity relationship. Conclusion: Structure-activity relationship analysis was performed to predict the therapeutic role of isolated compounds. These computational studies may be performed to minimize the efforts to determine the therapeutic role of natural compounds.

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CD38 as an immunomodulator in cancer

Future Oncology ◽

10.2217/fon-2020-0401 ◽

2020 ◽

Vol 16 (34) ◽

pp. 2853-2861

Author(s):

Yanli Li ◽

Rui Yang ◽

Limo Chen ◽

Sufang Wu

Keyword(s):

Multiple Myeloma ◽

Cell Activation ◽

Human Tissues ◽

Transmembrane Glycoprotein ◽

Cell Activation Marker ◽

Research Findings ◽

A Cell ◽

And Function ◽

Human Molecule

CD38 is a transmembrane glycoprotein that is widely expressed in a variety of human tissues and cells, especially those in the immune system. CD38 protein was previously considered as a cell activation marker, and today monoclonal antibodies targeting CD38 have witnessed great achievements in multiple myeloma and promoted researchers to conduct research on other tumors. In this review, we provide a wide-ranging review of the biology and function of the human molecule outside the field of myeloma. We focus mainly on current research findings to summarize and update the findings gathered from diverse areas of study. Based on these findings, we attempt to extend the role of CD38 in the context of therapy of solid tumors and expand the role of the molecule from a simple marker to an immunomodulator.

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Protease Inhibitors as Antiviral Agents

Clinical Microbiology Reviews ◽

10.1128/cmr.11.4.614 ◽

1998 ◽

Vol 11 (4) ◽

pp. 614-627 ◽

Cited By ~ 118

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.

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Human Coronaviruses: Counteracting the Damage by Storm

Viruses ◽

10.3390/v13081457 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1457

Author(s):

Dewald Schoeman ◽

Burtram C. Fielding

Keyword(s):

Immune Response ◽

Severe Disease ◽

Antiviral Agents ◽

The Elderly ◽

Highly Pathogenic ◽

Vaccine Responses ◽

Cell Mediated Immune Response ◽

Inhibition Antibody ◽

A Cell ◽

Human Coronaviruses

Over the past 18 years, three highly pathogenic human (h) coronaviruses (CoVs) have caused severe outbreaks, the most recent causative agent, SARS-CoV-2, being the first to cause a pandemic. Although much progress has been made since the COVID-19 pandemic started, much about SARS-CoV-2 and its disease, COVID-19, is still poorly understood. The highly pathogenic hCoVs differ in some respects, but also share some similarities in clinical presentation, the risk factors associated with severe disease, and the characteristic immunopathology associated with the progression to severe disease. This review aims to highlight these overlapping aspects of the highly pathogenic hCoVs—SARS-CoV, MERS-CoV, and SARS-CoV-2—briefly discussing the importance of an appropriately regulated immune response; how the immune response to these highly pathogenic hCoVs might be dysregulated through interferon (IFN) inhibition, antibody-dependent enhancement (ADE), and long non-coding RNA (lncRNA); and how these could link to the ensuing cytokine storm. The treatment approaches to highly pathogenic hCoV infections are discussed and it is suggested that a greater focus be placed on T-cell vaccines that elicit a cell-mediated immune response, using rapamycin as a potential agent to improve vaccine responses in the elderly and obese, and the potential of stapled peptides as antiviral agents.

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PapRIV, a BV-2 microglial cell activating quorum sensing peptide

Scientific Reports ◽

10.1038/s41598-021-90030-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yorick Janssens ◽

Nathan Debunne ◽

Anton De Spiegeleer ◽

Evelien Wynendaele ◽

Marta Planas ◽

...

Keyword(s):

Quorum Sensing ◽

Cell Model ◽

Dependent Manner ◽

Communication Signals ◽

Gram Positive Bacteria ◽

A Cell ◽

Gastro Intestinal Tract

AbstractQuorum sensing peptides (QSPs) are bacterial peptides produced by Gram-positive bacteria to communicate with their peers in a cell-density dependent manner. These peptides do not only act as interbacterial communication signals, but can also have effects on the host. Compelling evidence demonstrates the presence of a gut-brain axis and more specifically, the role of the gut microbiota in microglial functioning. The aim of this study is to investigate microglial activating properties of a selected QSP (PapRIV) which is produced by Bacillus cereus species. PapRIV showed in vitro activating properties of BV-2 microglia cells and was able to cross the in vitro Caco-2 cell model and reach the brain. In vivo peptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNFα and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-κB dependent manner. Different metabolites were identified in serum, of which the main metabolite still remained active. PapRIV is thus able to cross the gastro-intestinal tract and the blood–brain barrier and shows in vitro activating properties in BV-2 microglia cells, hereby indicating a potential role of this quorum sensing peptide in gut-brain interaction.

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