Effectiveness of Coronavirus Vaccines against Syndrome Coronavirus 2 (SARS-CoV-2) and Its New Variants

The widespread outbreak of coronavirus disease 2019 in late 2019 caused many people worldwide to die or suffer from certain clinical complications even after the recovery. The virus has many social and economic adverse effects. Studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have specified that spike, surface glycoprotein antigen, is considered as a major target to stimulate the immune system. This glycoprotein binds to the angiotensin-converting enzyme 2 on the surface of human cells especially lung epithelial cells and facilitates the virus entry. Therefore, the immune response stimulated by vaccination targeting this antigen may cause immunity against the whole virus. Currently, many companies are working on SARS-CoV-2 vaccines. They include ‘traditional’ vaccines like attenuated or inactivated virus platforms as well as the brand-new generations of vaccines such as viral vector-based, subunit, nucleic acid-based, and virus-like particle vaccines. Certainly, each vaccine platform presents several advantages and disadvantages affecting its efficacy and safety which is the main topic of this paper.

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Targeting transcriptional regulation of SARS-CoV-2 entry factors ACE2 and TMPRSS2

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2021450118 ◽

2020 ◽

Vol 118 (1) ◽

pp. e2021450118 ◽

Cited By ~ 1

Author(s):

Yuanyuan Qiao ◽

Xiao-Ming Wang ◽

Rahul Mannan ◽

Sethuramasundaram Pitchiaya ◽

Yuping Zhang ◽

...

Keyword(s):

Epithelial Cells ◽

Transcriptional Repression ◽

Lung Epithelial Cells ◽

Host Proteins ◽

Mortality And Morbidity ◽

Angiotensin Converting Enzyme 2 ◽

Transcriptional Inhibition ◽

Lung Epithelial ◽

Epidemiological Cohort

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, employs two key host proteins to gain entry and replicate within cells, angiotensin-converting enzyme 2 (ACE2) and the cell surface transmembrane protease serine 2 (TMPRSS2). TMPRSS2 was first characterized as an androgen-regulated gene in the prostate. Supporting a role for sex hormones, males relative to females are disproportionately affected by COVID-19 in terms of mortality and morbidity. Several studies, including one employing a large epidemiological cohort, suggested that blocking androgen signaling is protective against COVID-19. Here, we demonstrate that androgens regulate the expression of ACE2, TMPRSS2, and androgen receptor (AR) in subsets of lung epithelial cells. AR levels are markedly elevated in males relative to females greater than 70 y of age. In males greater than 70 y old, smoking was associated with elevated levels of AR and ACE2 in lung epithelial cells. Transcriptional repression of the AR enhanceosome with AR or bromodomain and extraterminal domain (BET) antagonists inhibited SARS-CoV-2 infection in vitro. Taken together, these studies support further investigation of transcriptional inhibition of critical host factors in the treatment or prevention of COVID-19.

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Preparation and evaluation of chitosan–DNA–FAP-B nanoparticles as a novel non-viral vector for gene delivery to the lung epithelial cells

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2011.02.043 ◽

2011 ◽

Vol 409 (1-2) ◽

pp. 307-313 ◽

Cited By ~ 30

Author(s):

Z. Mohammadi ◽

M. Abolhassani ◽

F.A. Dorkoosh ◽

S. Hosseinkhani ◽

K. Gilani ◽

...

Keyword(s):

Gene Delivery ◽

Epithelial Cells ◽

Viral Vector ◽

Lung Epithelial Cells ◽

Lung Epithelial ◽

Preparation And Evaluation

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Identification of the SARS-CoV-2 Entry Receptor ACE2 as a Direct Target for Transcriptional Repression by Miz1

Frontiers in Immunology ◽

10.3389/fimmu.2021.648815 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jing Yang ◽

Edith A. Perez ◽

Changchun Hou ◽

Pin Zhang ◽

Michelle Van Scoyk ◽

...

Keyword(s):

Epithelial Cells ◽

Angiotensin Converting Enzyme ◽

Cigarette Smoke ◽

Lung Epithelial Cells ◽

Cigarette Smoke Exposure ◽

Chronic Obstructive ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Copd Patients ◽

Lung Epithelial

Multiple lines of evidence have demonstrated that cigarette smoke or Chronic Obstructive Pulmonary Disease upregulates angiotensin-converting enzyme 2, the cellular receptor for the entry of the severe acute respiratory syndrome coronavirus 2, which predisposes individuals to develop severe Coronavirus disease 2019. The reason for this observation is unknown. We recently reported that the loss of function of Miz1 in the lung epithelium in mice leads to a spontaneous COPD-like phenotype, associated with upregulation of angiotensin-converting enzyme 2. We also reported that cigarette smoke exposure downregulates Miz1 in lung epithelial cells and in mice, and Miz1 is also downregulated in the lungs of COPD patients. Here, we provide further evidence that Miz1 directly binds to and represses the promoter of angiotensin-converting enzyme 2 in mouse and human lung epithelial cells. Our data provide a potential molecular mechanism for the upregulation of angiotensin-converting enzyme 2 observed in smokers and COPD patients, with implication in severe Coronavirus disease 2019.

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Pathophysiology and potential future therapeutic targets using preclinical models of COVID-19

ERJ Open Research ◽

10.1183/23120541.00405-2020 ◽

2020 ◽

Vol 6 (4) ◽

pp. 00405-2020

Author(s):

Rahul Kumar ◽

Michael H. Lee ◽

Claudia Mickael ◽

Biruk Kassa ◽

Qadar Pasha ◽

...

Keyword(s):

Distress Syndrome ◽

Surface Protein ◽

Lung Epithelial Cells ◽

Tissue Samples ◽

Angiotensin Converting Enzyme 2 ◽

Therapeutic Modalities ◽

Novel Treatment ◽

Lung Epithelial ◽

Host Inflammatory Response ◽

Selection Of

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) gains entry into the lung epithelial cells by binding to the surface protein angiotensin-converting enzyme 2. Severe SARS-CoV-2 infection, also known as coronavirus disease 2019 (COVID-19), can lead to death due to acute respiratory distress syndrome mediated by inflammatory immune cells and cytokines. In this review, we discuss the molecular and biochemical bases of the interaction between SARS-CoV-2 and human cells, and in doing so we highlight knowledge gaps currently precluding development of new effective therapies. In particular, discovery of novel treatment targets in COVID-19 will start from understanding pathologic changes based on a large number of autopsy lung tissue samples. Pathogenetic roles of potential molecular targets identified in human lung tissues must be validated in established animal models. Overall, this stepwise approach will enable appropriate selection of candidate therapeutic modalities targeting SARS-CoV2 and the host inflammatory response.

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An Oral Live Attenuated Vaccine Strategy against Severe Acute Respiratory Syndrome Coronavirus 2 (2019-nCoV)

10.20944/preprints202004.0153.v1 ◽

2020 ◽

Author(s):

Madhusudana Girija Sanal ◽

Ravi Chandra Dubey

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Herd Immunity ◽

Lung Epithelial Cells ◽

Vaccine Strategy ◽

Live Attenuated Vaccine ◽

Live Virus ◽

Angiotensin Converting Enzyme 2 ◽

Attenuated Vaccine ◽

Lung Epithelial ◽

Per Oral

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2/2019-nCoV) infection is an emerging pandemic. The virus binds to angiotensin converting enzyme 2 (ACE2) and TMPRSS2 which are abundantly expressed on various human cells including lung epithelial cells and intestinal cells and the virus can infect these cells. Currently no specific treatments or vaccines are available for this disease. A per oral live attenuated vaccine can be beneficial in SARS-Cov-2 infection because the attenuated virus initially infects the gut, stimulates the mucosa associated immune system sparing the respiratory system during the initial immune response. The live virus can also spread in the community boosting herd immunity.

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An oral live attenuated vaccine strategy against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/2019-nCoV)

Research Ideas and Outcomes ◽

10.3897/rio.6.e53767 ◽

2020 ◽

Vol 6 ◽

Cited By ~ 1

Author(s):

Madhusudana Girija Sanal ◽

Ravi Chandra Dubey

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Herd Immunity ◽

Lung Epithelial Cells ◽

Vaccine Strategy ◽

Live Attenuated Vaccine ◽

Live Virus ◽

Angiotensin Converting Enzyme 2 ◽

Attenuated Vaccine ◽

Lung Epithelial ◽

Per Oral

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/2019-nCoV) infection has become a pandemic called COVID-19. The virus binds to angiotensin converting enzyme 2 (ACE2) and TMPRSS2 which are abundantly expressed on various human cells including lung epithelial cells and intestinal cells and the virus can infect these cells. Currently no specific treatments or vaccines are available for this disease. A per oral live attenuated vaccine can be a good strategy in SARS-CoV-2 infection because the attenuated virus initially infects the gut, stimulates the mucosa associated immune system sparing the respiratory system during the initial immune response. The live virus can also spread in the community boosting herd immunity.

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