Current pharmaceutical design
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Recent emergence of COVID-19 caused by a new human coronavirus (CoV) strain (SARS-CoV-2), which originated from China, poses the future emergence of additional CoVs. In most of the cases of emergence of human CoVs, bats, palm civets, raccoon dogs and camels have been identified as the sources of human infections and as reservoir hosts. A review of comparative genomic and phenotypic characteristics of human CoV strains vis-à-vis their comparison with the corresponding animal isolates shall provide clues regarding the potential genomic, phenotypic and molecular factors responsible for host-switching, which may lead to prospective emergence and re-emergence of human CoV outbreaks in the future. ⋯ High propensity of mutations and "molecular adaptations" in coronaviruses creates the hot spots and high potential for "host switching", leading to the emergence of more virulent strains of human CoVs. The public/global health agencies, medical communities and research scientists should be prepared for the emergence and re-emergence of new human CoV strain(s) leading to potential disease outbreaks. The inhibitors binding with conserved druggable regions of spike proteins from multiple strains CoV may have utility as broad-spectrum antiviral drugs to combat future emergence of CoVs.
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Tocilizumab is a humanised interleukin-6 receptor-inhibiting monoclonal antibody that is currently approved for the treatment of rheumatoid arthritis and other immune-related conditions. Recently, tocilizumab has been investigated as a possible treatment for severe coronavirus-induced disease 2019 (COVID-19). Despite the lack of direct antiviral effects, tocilizumab could reduce the immune-induced organ damage caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) infection. ⋯ We searched the MEDLINE database with the string "(SARS-CoV-2 OR coronavirus OR COVID-19 OR MERS- cov OR SARS-cov) AND (IL-6 OR interleukin 6 OR tocilizumab)". While the scientific rationale supporting tocilizumab for COVID-19 is solid, the evidence regarding the outcomes remains controversial. Available data and results from ongoing trials will provide useful information in the event of new COVID-19 outbreaks or future pandemics from different coronaviruses.
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The antagonistic relationship between adenosine monophosphate-activated protein kinase (AMPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling play a vital role in cancer development. The anti-cancer effects of berberine have been reported as a main component of the traditional Chinese medicine Rhizoma coptidis, although the roles of these signaling pathways in these effects have not been systematically reviewed. ⋯ This evidence supports the possibility that berberine is a promising anti-cancer natural product, with pharmaceutical potential in inhibiting cancer growth, metastasis and angiogenesis via multiple pathways, particularly by regulating the balance of AMPK and PI3K/AKT signaling. However, systematic preclinical studies are still required to provide scientific evidence for further clinical studies.
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Human coronaviruses (HCoV) are common viruses and known to be associated with respiratory diseases, including pneumonia. Currently, seven human coronaviruses have been identified and known to cause upper and lower respiratory infections as well as nosocomial viral infections in humans. The bats, palm civets, and camels are identified as the reservoir of human coronaviruses. In 2002-2003, the emergence of SARS-CoV resulted in an outbreak and led towards the more awareness and importance of scientific research and medical urgency. ⋯ The plant lectins are known to have significant antiviral activities against coronaviruses. Additionally, the plant lectins can be used as potential therapeutics against bacteria, fungus, yeast, and protozoa. In this review, we have discussed the current status of human pathogenic coronavirus emergence and the use of plant lectins as antivirals against SARS-CoV-2.
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Chloroquine (CQ) and hydroxychloroquine (HCQ) are derivatives of the heterocyclic aromatic compound quinoline. These economical compounds have been used as antimalarial agents for many years. Currently, they are used as monotherapy or in conjunction with other therapies for the treatment of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome (SS) and antiphospholipid antibody syndrome (APS). ⋯ Several mechanisms have been proposed to explain the pharmacological effects of these drugs: 1) disruption of lysosomal and endosomal pH, 2) inhibition of protein secretion/expression, 3) inhibition of antigen presentation, 4) decrease of proinflammatory cytokines, 5) inhibition of autophagy, 6) induction of apoptosis and 7) inhibition of ion channels activation. Thus, evidence has shown that these structures are leading molecules that can be modified or combined with other therapeutic agents. In this review, we will discuss the most recent findings in the mechanisms of action of CQ and HCQ in the immune system, and the use of these antimalarial drugs on diseases.