Targeting Host Cell Proteases to Prevent SARS-CoV-2 Invasion

Kaur, Upinder; Chakrabarti, Sankha Shubhra; Ojha, Bisweswar; Pathak, Bhairav Kumar; Singh, Amit Kumar; Saso, Luciano; Chakrabarti, Sasanka

doi:10.2174/1389450121666200924113243

Cited by 35 publications

(34 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Vaccine development and disbursal should also be focused on vulnerable groups. Although not entirely relevant in the present discussion, we suggest that drug repurposing and trials on low cost medications such as hydroxychloroquine, ivermectin, bromhexine, ammonium chloride, angiotensin converting enzyme inhibitors, and anticoagulants must be priority research areas, rather than fixation on drugs such as remdesivir and tocilizumab which create major financial burden on the already stretched health resources of the country [ 17 , 18 ].…”

Section: A Covid Plan Specific To Indiamentioning

confidence: 99%

Of Cross-immunity, Herd Immunity and Country-specific Plans: Experiences from COVID-19 in India

Chakrabarti¹,

Kaur²,

Singh³

et al. 2020

Aging and disease

Self Cite

View full text Add to dashboard Cite

India has witnessed a high number of COVID-19 cases, but mortality has been quite low, and most cases have been asymptomatic or mild. In early April, we had hypothesized a low COVID-19 mortality in India, based on the concept of cross-immunity. The presence of cross-immunity is presumed to lead to a milder course of disease and allow the time necessary for the development of adaptive immunity by the body to eliminate the virus. Evidence supporting our hypothesis has started showing up. Multiple studies have shown the generation of different T cell subsets and B cells responding to epitopes of viral proteins, especially of the spike protein, as a part of adaptive immunity against SARS-CoV-2. Cross-reactive T-cells have been demonstrated in patients who have been previously exposed to endemic coronaviruses. The interplay of cross-immunity and herd immunity is apparent in the COVID-19 scenario in India from the presence of a large number of asymptomatic or mild cases, a low infection-fatality ratio and a generally flat curve of percentage positivity of cases with respect to total testing, both in periods of strict lock-down and step-wise unlocking. It seems that cross-immunity resulted in faster generation of herd immunity. Although the initial restrictive measures such as lockdown prevented the rapid spread of the outbreak, further extension of such measures and overly expensive ones such as enhanced testing in India will result in a huge burden on the health economics as well as the society. Hence, we propose a restructuring of the health services and approach to COVID-19. The restructured health services should move away from indiscriminate testing, isolation and quarantine, and instead, the emphasis should be on improving facilities for testing and management of only critical COVID cases and the replacement of complete lockdowns by the selective isolation and quarantine of susceptible persons such as the aged and those with co-morbidities. In the process of describing India-specific plans, we emphasize why the development of country-specific plans for tackling epidemics is important, instead of adopting a "one policy fits all" approach.

show abstract

Section: A Covid Plan Specific To Indiamentioning

confidence: 99%

Of Cross-immunity, Herd Immunity and Country-specific Plans: Experiences from COVID-19 in India

Chakrabarti¹,

Kaur²,

Singh³

et al. 2020

Aging and disease

Self Cite

View full text Add to dashboard Cite

show abstract

“…This furin cleavage site has a unique insertion enabling cleavage of spike protein of just the SARS-CoV-2, and not the related SARS-CoV-1 or the Middle East Respiratory Syndrome coronavirus MERS-CoV [ 142 ]. This information has led to the identification of furin inhibition as a strategy to limit SARS-CoV-2 infection [ 143 , 144 ]. Furin has also been investigated in lung cancer and was reported to be expressed in all the tumors, with particularly elevated levels in NSCLC, the more common lung cancer subtype, relative to the small cell lung carcinomas [ 145 ].…”

Section: Lung Cancer and Covid-19: The Molecular Linkmentioning

confidence: 99%

Epigenetic underpinnings of inflammation: Connecting the dots between pulmonary diseases, lung cancer and COVID-19

Ahmad

Manzoor

Siddiqui

et al. 2022

Seminars in Cancer Biology

View full text Add to dashboard Cite

Inflammation is an essential component of several respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma and acute respiratory distress syndrome (ARDS). It is central to lung cancer, the leading cancer in terms of associated mortality that has affected millions of individuals worldwide. Inflammation and pulmonary manifestations are also the major causes of COVID-19 related deaths. Acute hyperinflammation plays an important role in the COVID-19 disease progression and severity, and development of protective immunity against the virus is greatly sought. Further, the severity of COVID-19 is greatly enhanced in lung cancer patients, probably due to the genes such as ACE2, TMPRSS2, PAI-1 and furin that are commonly involved in cancer progression as well as SAR-CoV-2 infection. The importance of inflammation in pulmonary manifestations, cancer and COVID-19 calls for a closer look at the underlying processes, particularly the associated increase in IL-6 and other cytokines, the dysregulation of immune cells and the coagulation pathway. Towards this end, several reports have identified epigenetic regulation of inflammation at different levels. Expression of several key inflammation-related cytokines, chemokines and other genes is affected by methylation and acetylation while non-coding RNAs, including microRNAs as well as long non-coding RNAs, also affect the overall inflammatory responses. Select miRNAs can regulate inflammation in COVID-19 infection, lung cancer as well as other inflammatory lung diseases, and can serve as epigenetic links that can be therapeutically targeted. Furthermore, epigenetic changes also mediate the environmental factors-induced inflammation. Therefore, a better understanding of epigenetic regulation of inflammation can potentially help develop novel strategies to prevent, diagnose and treat chronic pulmonary diseases, lung cancer and COVID-19.

show abstract

“…The virus with the help of the viral spike protein (S) binds with angiotensin II converting enzyme 2 (ACE2) receptors present on the membranes of the host cells, and this process requires the priming of S protein by two proteolytic cleavages with the help of a host-cell serine protease called TMPRSS2 [ 27 , 28 ]. Several other proteases (host or virus-derived) are involved in the binding and internalization of the virus and its subsequent maturation within the cells [ 29 ]. Within the cells, the positive single-strand viral genomic RNA is first translated to produce two polyproteins which are cleaved to generate several non-structural proteins of SARS-CoV-2 that assemble to form the replication/transcription machinery that helps to produce finally positive-strand genomic RNA and many subgenomic RNAs (+) coding for viral structural proteins [ 25 ].…”

Section: Pathogenesis and Pathology Of Covid-19mentioning

confidence: 99%

Vitamin D and immuno-pathology of COVID-19: many interactions but uncertain therapeutic benefits

Banerjee

Ganguly

Saha

et al. 2021

Expert Review of Anti-infective Therapy

Self Cite

View full text Add to dashboard Cite

Introduction : COVID-19 pandemic has caused huge loss of human lives and extensive socio-economic damages. The immuno-pathology of this disease is neither clearly understood nor there are effective drugs for severe cases of COVID-19. Repurposing of available drugs for the treatment of COVID-19 is imperative. Areas Covered : This review has gathered the evidence from PubMed, Google Scholar, WHO, and other reliable websites on COVID-19 and summarized the existing knowledge of the immuno-pathology of COVID-19. We elucidated how vitamin D through its diverse actions on immune effector cells, epithelial cells, or renin-angiotensin-aldosterone system could have a modulatory role on the pathogenic mechanisms of COVID-19. The epidemiological evidence associating vitamin D deficiency with the severity and incidence of COVID-19 is also presented. However, the evidence of clinical benefit to patients of COVID-19 from randomized controlled trials with vitamin D has not come as yet. Expert opinion : It is now established that fatality of COVID-19 is primarily determined by hyperactivation of the host’s innate immune system in response to SARS-CoV-2 invasion, and thus the research on the immuno-modulatory and other roles of vitamin D against viral infections should be pursued vigorously. This would be also useful for future pandemics caused by other novel viruses.

show abstract

Targeting Host Cell Proteases to Prevent SARS-CoV-2 Invasion

Cited by 35 publications

References 45 publications

Of Cross-immunity, Herd Immunity and Country-specific Plans: Experiences from COVID-19 in India

Of Cross-immunity, Herd Immunity and Country-specific Plans: Experiences from COVID-19 in India

Epigenetic underpinnings of inflammation: Connecting the dots between pulmonary diseases, lung cancer and COVID-19

Vitamin D and immuno-pathology of COVID-19: many interactions but uncertain therapeutic benefits

Contact Info

Product

Resources

About