scholarly journals Can ChAdOx1, a replication-deficient adenoviral (Ad) vector used to deliver SARS-Cov2 spike protein as a vaccine, recombine with the homologous human Ad to generate a novel Ad+Spike virus?

2020 ◽  
Author(s):  
Sandeep Chakraborty
Keyword(s):  
Viral Vector ◽  
Rna Virus ◽  
Human Adenovirus ◽  
Cell Receptor ◽  
Spike Protein ◽  
Transcriptional Unit ◽  
Human Virus ◽  
Dna And Rna ◽  
Host Cell Receptor ◽  
Weakened Version

The development of a vaccine for Covid19 is being expedited [1]. The underlying technology for the vaccines are varied: ‘nucleic acid (DNA and RNA), virus-like particle, peptide, viral vector (replicating and non- replicating), recombinant protein, live attenuated virus and inactivated virus’ [2]. Among these, ChAdOx1, a genetically modified, weakened version of a common cold virus (adenovirus) is now in human clinical trials [3]. The ChAd vector (Chimpanzee adenovirus) was introduced in 2012 Chimpanzee adenovirus Y25 [4]. A large proportion of human adults possess significant titres of neutralising antibodies to human Adv, hence the requirement for a different adenovirus. The deletion of a single transcriptional unit, E1, ensures these viruses cant replicate. Other genes like the E3 region may also be deleted. Now, in the Covid19 vaccine ChAdOx1, the spike protein gene from MERS-CoV strain Camel/Qatar/2/2014 ‘was inserted into the E1 locus of a genomic clone of ChAdOx1 using site-specific recombination’ [5].One of the theories about the genesis of SARS-Cov2 is recombination with coronaviruses from pan- golins [6]. Whether or not it happened in SARS-Cov2, there is no denying that such recombinations do happen.How do we know that the spike protein wont be inserted into a human adenovirus using recombination?Human adenovirus shares 95% homology to ChAd. The spike protein may be inserted after the E1 protein in a viable human virus. What will happen after that to the virus is anyone’s guess. Note, that there is precedence for such recombinant adenoviruses - using ‘ping-pong” zoonosis and anthroponosis’, where the genome of a promiscuous pathogen is ‘embedded with evidence of unprecedented multiple, multidirectional, stable, and reciprocal cross-species infections of hosts from three species (human, chimpanzee, and bonobo)’ [7].Another critique - co-stimulation in host cellsA spike protein from SARS-Cov2, which is supposed to bind to ACE2 and CD147 [8], has been inserted in an adenovirus. The adenovirus has its own host-cell receptor preferences [9] - what will be the consequences of co-stimulation in those cells in which both these receptors are expressed?

Herbal Medicine in Fighting Against COVID-19: New Battle with an Old Weapon

2021 ◽  
Vol 22 ◽  
Author(s):  
Ranjit K. Harwansh ◽  
Shiv Bahadur
Keyword(s):  
Herbal Medicine ◽  
Rna Virus ◽  
Plant Secondary Metabolites ◽  
Cell Receptor ◽  
Inhibitory Effect ◽  
World Population ◽  
Main Process ◽  
Potential Health ◽  
Host Cell Receptor ◽  
Novel Coronavirus

: World population has been suffering due to the outbreak of present pandemic situation of COVID-19. The disease has become life-threatening in a very short time with touching on most of the citizenry and economic systems globally. The novel virus, SARS-CoV-2 has been known as the causative agent of COVID-19. The SARS-CoV-2 is single stranded RNA virus having ~30 kb genomic components which are 70% identical to SARS-CoV. The main process of pathophysiology of COVID-19 has been associated with the interaction of a novel coronavirus with host cell receptor, angiotensin-converting enzyme-2 (ACE 2) by fusion. Therapeutic agents having serine protease inhibitors and ACE-2 blockers may be explored for the treatment by inhibiting the viral target such as Mpro, RdRp, PLpro and helicase. Herbal medicine has a wide array chemical entity with potential health benefits including antiviral activity which may be explored as alternative treatment of COVID-19. The herbal bioactives like catechins, andrographolide, hesperidin, biorobin, scutellarein, silvestrol, shikonin, tryptanthrin, vitexin quercetin, myricetin, caffeic acid, psoralidin, luteolin etc have showed potential inhibitory effect against SARS-CoV-2. Recent research reports indicate that the various plant secondary metabolites have shown the potential antiviral activities. The present review article highlights on the recent information on the mechanism of actions and applications of herbal medicine in the treatment of COVID-19.

scholarly journals CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Ke Wang ◽  
Wei Chen ◽  
Zheng Zhang ◽  
Yongqiang Deng ◽  
Jian-Qi Lian ◽  
...  
Keyword(s):  
Virus Entry ◽  
Rapid Evolution ◽  
Cell Receptor ◽  
Host Cells ◽  
Spike Protein ◽  
Dependent Manner ◽  
Viral Loads ◽  
Host Cell Receptor ◽  
Human T Cells ◽  
Effective Drugs

AbstractIn face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2, no specific and effective drugs for treating this disease have been reported until today. Angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2, mediates the virus infection by binding to spike protein. Although ACE2 is expressed in the lung, kidney, and intestine, its expressing levels are rather low, especially in the lung. Considering the great infectivity of COVID-19, we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection. Here, we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein. The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody, Meplazumab, inhibits SARS-CoV-2 amplification. Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells, which can be neutralized by CD147 extracellular fragment. Viral loads are detectable in the lungs of human CD147 (hCD147) mice infected with SARS-CoV-2, but not in those of virus-infected wild type mice. Interestingly, virions are observed in lymphocytes of lung tissue from a COVID-19 patient. Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dose-dependent manner, which is specifically inhibited by Meplazumab. Furthermore, CD147 mediates virus entering host cells by endocytosis. Together, our study reveals a novel virus entry route, CD147-spike protein, which provides an important target for developing specific and effective drug against COVID-19.

scholarly journals An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike

Science ◽  
2020 ◽  
pp. eabe3255 ◽  
Author(s):  
Michael Schoof ◽  
Bryan Faust ◽  
Reuben A. Saunders ◽  
Smriti Sangwan ◽  
Veronica Rezelj ◽  
...  
Keyword(s):  
Cell Receptor ◽  
Affinity Maturation ◽  
Host Cells ◽  
Spike Protein ◽  
Airway Epithelia ◽  
Angiotensin Converting Enzyme 2 ◽  
Inactive Conformation ◽  
Binding Domains ◽  
Host Cell Receptor ◽  
Yeast Surface

The SARS-CoV-2 virus enters host cells via an interaction between its Spike protein and the host cell receptor angiotensin converting enzyme 2 (ACE2). By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt the interaction between Spike and ACE2. Cryogenic electron microscopy (cryo-EM) revealed that one nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains (RBDs) locked into their inaccessible down-state, incapable of binding ACE2. Affinity maturation and structure-guided design of multivalency yielded a trivalent nanobody, mNb6-tri, with femtomolar affinity for Spike and picomolar neutralization of SARS-CoV-2 infection. mNb6-tri retains function after aerosolization, lyophilization, and heat treatment, which enables aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia.

scholarly journals Host-cell recognition through GRP78 is enhanced in the new UK variant of SARS-CoV-2, in silico 

2021 ◽  
Author(s):  
Abdo A Elfiky ◽  
Ibrahim M Ibrahim
Keyword(s):  
Host Cell ◽  
Cell Receptor ◽  
Spike Protein ◽  
Cell Recognition ◽  
Receptor Binding Domain ◽  
Host Cell Receptor ◽  
Mutant Variant ◽  
New Variant ◽  
The Uk ◽  
Host Cell Recognition

Abstract New SARS-CoV-2 variant VUI 202012/01 started in the UK and currently spreading in Europe and Australia during the last few days. The new variant bears about nine mutations in the spike protein (Δ69-70, Δ145, N501Y, A570D, D614G, P681H, T716I, S982A, and D1118H). The N501Y lies in the receptor-binding domain (RBD) of the spike and interacts with the host-cell receptor ACE2 responsible for viral recognition and entry. We tried to simulate the system of ACE2-SARS-CoV-2 spike RBD in the wildtype and mutated isoform of the RBD (N501Y). Additionally, the GRP78 association with the ACE2-SARS-CoV-2 spike RBD is modeled at the presence of this mutant variant of the viral spike.

An overview on transmission of diseases in special reference to COVID-19 and potential targets to control this pandemic

2020 ◽  
pp. 05-14
Author(s):  
Vibha Yadav ◽  
Mrigendra Rajput ◽  
Diwakar R.P ◽  
Rajesh Kumar
Keyword(s):  
Rna Virus ◽  
Close Contact ◽  
Adaptive Immune Response ◽  
Cell Receptor ◽  
Angiotensin Converting Enzyme 2 ◽  
Infected People ◽  
Adaptive Immune ◽  
Host Cell Receptor ◽  
Positive Sense ◽  
Respiratory Droplets

With its initial outbreak in China, the virus was referred as "coronavirus". WHO has named it "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). It has been described as the successor to SARS-CoV-1which is a positive-sense single-stranded RNA virus. The virus spreads mainly between people who are in close contact (less than two metres or six feet) through small droplets produced during coughing, sneezing, or talking. Infected people exhale the contaminated droplets which are then inhaled into the lungs, or settle on other non- infected people's faces his/her mucosae (mouth and nose) or conjunctiva (eyes) get exposed to potentially infective respiratory droplets to cause new infection. It mainly enters human cells by binding to the receptor angiotensin converting enzyme 2 (ACE2). Research works are in progress to find potential targets to control the pandemic. To control and treat the virus various targets are under study and these targets range from modulating host cell receptor for the virus entry to generate an effective adaptive immune response.

scholarly journals Lions, tigers and kittens too: ACE2 and susceptibility to COVID-19

2020 ◽  
Vol 2020 (1) ◽  
pp. 109-113 ◽  
Author(s):  
Sabateeshan Mathavarajah ◽  
Graham Dellaire
Keyword(s):  
Crystal Structure ◽  
Amino Acid ◽  
Cell Receptor ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Host Cell Receptor ◽  
Specific Manner ◽  
Species Specific ◽  
Computational Analyses

Abstract SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2) has been reported to infect domesticated animals in a species-specific manner, where cats were susceptible but not dogs. Using the recently published crystal structure of the SARS-CoV-2 spike protein complexed with the human host cell receptor angiotensin converting enzyme 2 (ACE2), we characterized the structure and evolution of ACE2 in several of these species and identify a single interacting amino acid residue conserved between human and Felidae ACE2 but not in Canidae that correlates with virus susceptibility. Using computational analyses we describe how this site likely affects ACE2 targeting by the virus. Thus, we highlight how evolution-based approaches can be used to form hypotheses and study animal transmission of such viruses in the future.

scholarly journals Dynamical asymmetry exposes 2019-nCoV prefusion spike

2020 ◽  
Author(s):  
Susmita Roy
Keyword(s):  
Host Cell ◽  
Cell Receptor ◽  
Spike Protein ◽  
The Novel ◽  
Structural Topology ◽  
Dynamic Simulations ◽  
Asymmetric Structures ◽  
Host Cell Receptor ◽  
Model Hamiltonian ◽  
Novel Coronavirus

AbstractThe novel coronavirus (2019-nCoV) spike protein is a smart molecular machine that instigates the entry of coronavirus to the host cell causing the COVID-19 pandemic. In this study, a structural-topology based model Hamiltonian of C3 symmetric trimeric spike is developed to explore its complete conformational energy landscape using molecular dynamic simulations. The study finds 2019-nCoV to adopt a unique strategy by undertaking a dynamic conformational asymmetry induced by a few unique inter-chain interactions. This results in two prevalent asymmetric structures of spike where one or two spike heads lifted up undergoing a dynamic transition likely to enhance rapid recognition of the host-cell receptor turning on its high-infectivity. The crucial interactions identified in this study are anticipated to potentially affect the efficacy of therapeutic targets.One Sentence SummaryInter-chain-interaction driven rapid symmetry breaking strategy adopted by the prefusion trimeric spike protein likely to make 2019-nCoV highly infective.

Understanding the Role of Corona Virus based on Current Scientific Evidence - A Review with Emerging Importance in Pandemic

2020 ◽  
Vol 15 (2) ◽  
pp. 89-103
Author(s):  
Suman K. Ray ◽  
Sukhes Mukherjee
Keyword(s):  
Host Cell ◽  
Scientific Evidence ◽  
Antibody Therapy ◽  
Cell Receptor ◽  
Spike Protein ◽  
Virus Infectivity ◽  
Angiotensin Converting Enzyme 2 ◽  
Host Cell Receptor ◽  
Antiviral Medications

: Coronavirus disease is a potentially deadly disease and of significant apprehension for global communal health because of its lethality. Vaccines and antiviral medications are still under trial to prevent or treat human coronavirus (HCoV) till date. The virus HCoV originated in 2003, SARS-CoV, which causes respiratory syndrome having distinctive pathogenesis and infections of the respiratory tract. A mechanism was projected for the evolution of SARS virus, and a handy association with bats was found. When this virus reaches the respective host system, the infection starts with spike protein binding to its complementary receptor of the host cell. The coronavirus spike protein’s association with its host cell receptor complement is crucial in deciding the virus infectivity, tissue tropism and species variety. Recent studies show that SARS Coronavirus 2 or COVID-19 requires protease to get into cells, offering a new therapeutic target. Distinctive attention and exertions should be given to defending or reducing transmission in vulnerable populaces, including those directly associated with caregiving and treatment and also aged one. Researchers are planning to develop a vaccine for COVID-19, and in this approach are also considered developing a vaccine that sensitizes our immune system preventing from this pandemic. The present review focuses on the role of S-spike protein in COVID-19, which helps the virus intruding the enzyme ACE2 (Angiotensin-Converting Enzyme 2). Passive antibody therapy is an additional alternative to use blood donors from hale and hearty people who have already recovered from COVID-19 and therapeutic advancement in handling the COVID-19 pandemic.

Role of bacteriophage SPP1 tail spike protein gp21 on host cell receptor binding and trigger of phage DNA ejection

2011 ◽  
Vol 83 (2) ◽  
pp. 289-303 ◽  
Author(s):  
Inês Vinga ◽  
Catarina Baptista ◽  
Isabelle Auzat ◽  
Isabelle Petipas ◽  
Rudi Lurz ◽  
...  
Keyword(s):  
Host Cell ◽  
Receptor Binding ◽  
Cell Receptor ◽  
Spike Protein ◽  
Host Cell Receptor ◽  
Dna Ejection ◽  
Phage Dna ◽  
Tail Spike

scholarly journals An Overview On Transmission Of Diseases In Special Reference To COVID-19 And Potential Targets To Control This Pandemic

2020 ◽  
Vol 4 (1) ◽  
pp. 1-6
Author(s):  
Vibha Yadav ◽  
Keyword(s):  
Rna Virus ◽  
Close Contact ◽  
Adaptive Immune Response ◽  
Cell Receptor ◽  
Angiotensin Converting Enzyme 2 ◽  
Infected People ◽  
Adaptive Immune ◽  
Host Cell Receptor ◽  
Positive Sense ◽  
Respiratory Droplets

With its initial outbreak in China, the virus was referred as "coronavirus". WHO has named it "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). It has been described as the successor to SARS-CoV-1 which is a positive-sense single-stranded RNA virus. The virus spreads mainly between people who are in close contact (less than two metres or six feet) through small droplets produced during coughing, sneezing, or talking. Infected people exhale the contaminated droplets which are then inhaled into the lungs, or settle on other non- infected people's faces his/her mucosae (mouth and nose) or conjunctiva (eyes) get exposed to potentially infective respiratory droplets to cause new infection. Organism may enter to human cells by binding to the receptor angiotensin converting enzyme 2 (ACE2). Research works are in progress to find potential targets to control the pandemic. To control and treat the virus various targets are under study and these targets range from modulating host cell receptor for the virus entry to generate an effective adaptive immune response.

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