Background: Currently, novel coronavirus disease (Covid-19) outbreak creates global panic across the continents, as people from almost all countries and territories have been affected by this highly contagious viral disease. The scenario is deteriorating due to lack of proper & specific target-oriented pharmacologically safe prophylactic agents or drugs, and or any effective vaccine. drug development is urgently required to back in the normalcy in the community and to combat this pandemic.
Purpose: Thus, we have proposed two novel drug targets, Furin and TMPRSS2, as Covid-19 treatment strategy. We have highlighted this target-oriented novel drug delivery strategy, based on their pathophysiological implication on SARS-CoV-2 infection, as evident from earlier SARS-CoV-1, MERS, and influenza virus infection via host cell entry, priming, fusion, and endocytosis. STUDY DESIGN & METHODS: An earlier study suggested that Furin and TMPRSS2 knockout mice had reduced level of viral load and a lower degree of organ damage such as the lung. The present study thus highlights the promise of some selected novel and potential anti-viral Phytopharmaceutical that bind to Furin and TMPRSS2 as target.
Result: Few of them had shown promising anti-viral response in both preclinical and clinical study with acceptable therapeutic safety-index.
Conclusion: Hence, this strategy may limit life-threatening Covid-19 infection and its mortality rate through nano-suspension based intra-nasal or oral nebulizer spray, to treat mild to moderate SARS-COV-2 infection when Furin and TMPRSS2 receptor may initiate to express and activate for processing the virus to cause cellular infection by replication within the host cell and blocking of host-viral interaction.
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http://dx.doi.org/10.1016/j.phymed.2020.153396 | DOI Listing |
J Biomol Struct Dyn
January 2025
Laboratory of Biology and Health, URAC 34, Faculty of Sciences, Ben M'Sik Hassan II University of Casablanca, Casablanca, Morocco.
The recent spread of SARS-CoV-2 has led to serious concerns about newly emerging infectious coronaviruses. Drug repurposing is a practical method for rapid development of antiviral agents. The viral spike protein of SARS-CoV-2 binds to its major receptor ACE2 to promote membrane fusion.
View Article and Find Full Text PDFmBio
November 2024
Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA.
Int J Biol Macromol
November 2024
Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada. Electronic address:
Furin cleavage site (FCS) of the SARS-CoV-2 S protein, which connects the S1/S2 junction, is essential for facilitating fusion with the host cells. Wild-type (Wt) SARS-CoV-2 S protein, PDB ID: 6yvb, lacks a sequence of amino acid residues, including the FCS that links the S1/S2 junction. For the first time, we demonstrated that a stretch of 14 amino acid residues (677QTNSPRRARSVASQ689) forms an antiparallel β-sheet comprising of PRRAR sequence in the FCS within a short loop.
View Article and Find Full Text PDFCureus
August 2024
Molecular Biology and Genetics, Muğla Sıtkı Koçman University Faculty of Medicine, Muğla, TUR.
The COVID-19 pandemic caused by the SARS-CoV-2 virus has been studied predominantly in terms of its immediate respiratory and systemic effects. However, emerging evidence suggests possible long-term effects, including its role in carcinogenesis. This comprehensive review explores the complex relationship between COVID-19 and cancer development, focusing on immune dysregulation, chronic inflammation, genetic and epigenetic alterations, and the impact of therapeutic interventions.
View Article and Find Full Text PDFPart Fibre Toxicol
September 2024
Advanced Environmental Research Institute, Department of Biological Sciences, University of North Texas, EESAT - 215, 1704 W. Mulberry, Denton, TX, 76201, USA.
Background: Both exposure to air pollutants and obesity are associated with increased incidence and severity of COVID-19 infection; however, the mechanistic pathways involved are not well-characterized. After being primed by the transmembrane protease serine 2 (TMPRSS2) or furin protease, SARS-CoV-2 uses the angiotensin-converting enzyme (ACE)-2 receptor to enter respiratory epithelial cells. The androgen receptor (AR) is known to regulate both TMPRSS2 and ACE2 expression, and neuropilin-1 (NRP1) is a proposed coreceptor for SARS-CoV-2; thus, altered expression of these factors may promote susceptibility to infection.
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