Design, synthesis and biological evaluations of niclosamide analogues against SARS-CoV-2

Juang, Yu-Pu; Chou, Yu-Ting; Lin, Rongheng; Ma, Hsiu-Hua; Chao, Tai‐Ling; Jan, Jia-Tsrong; Chang, Sui‐Yuan; Liang, Pi‐Hui

doi:10.1016/j.ejmech.2022.114295

Cited by 13 publications

(10 citation statements)

References 23 publications

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“… 534 It inhibits SARS-CoV-2 virus entry through TMEM16F inhibition and replication through autophagy induction. 535 , 536 Weiss et al showed that niclosamide potency is conserved against the Alpha, Beta, and Delta SARS-CoV-2 variants in Vero TMPRSS2 cells and the strong antiviral activity of niclosamide was validated in a human airway epithelial model. 537 An inhaled niclosamide formulation was developed and tested in a murine infection model of SARS-CoV-2.…”

Section: Structures Of Small Molecule Drugs For Covid-19 Therapymentioning

confidence: 99%

Small molecules in the treatment of COVID-19

Lei

Chen

Jin

et al. 2022

Sig Transduct Target Ther

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The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies and economies. Until now, effective therapeutics against COVID-19 are in high demand. Along with our improved understanding of the structure, function, and pathogenic process of SARS-CoV-2, many small molecules with potential anti-COVID-19 effects have been developed. So far, several antiviral strategies were explored. Besides directly inhibition of viral proteins such as RdRp and Mpro, interference of host enzymes including ACE2 and proteases, and blocking relevant immunoregulatory pathways represented by JAK/STAT, BTK, NF-κB, and NLRP3 pathways, are regarded feasible in drug development. The development of small molecules to treat COVID-19 has been achieved by several strategies, including computer-aided lead compound design and screening, natural product discovery, drug repurposing, and combination therapy. Several small molecules representative by remdesivir and paxlovid have been proved or authorized emergency use in many countries. And many candidates have entered clinical-trial stage. Nevertheless, due to the epidemiological features and variability issues of SARS-CoV-2, it is necessary to continue exploring novel strategies against COVID-19. This review discusses the current findings in the development of small molecules for COVID-19 treatment. Moreover, their detailed mechanism of action, chemical structures, and preclinical and clinical efficacies are discussed.

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Section: Structures Of Small Molecule Drugs For Covid-19 Therapymentioning

confidence: 99%

Small molecules in the treatment of COVID-19

Lei

Chen

Jin

et al. 2022

Sig Transduct Target Ther

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“…The best result among these was displayed by compound XXVI, an IC 50 value of 6.38 μM. Juang et al 68 explored niclosamide analogs based on aniline moiety, and the potent hit (XXVII) of their series exhibited an IC 50 value of 0.057 μM ( Fig. 4 ) against SARS-CoV-2 infection.…”

Section: Biological Efficacy Of Peptide Based Compounds Synthesized S...mentioning

confidence: 99%

Recent updates on the biological efficacy of approved drugs and potent synthetic compounds against SARS-CoV-2

2023

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“…Include drugs like Niclosamide, a widely used anthelmintic agent that inhibits PS externalization, averting both viral fusion with host cells and pathological cell-cell fusion [239,240].…”

Section: Tmem16f Inhibitorsmentioning

confidence: 99%

“…Senescent and cancer cells can avert elimination by expressing CD47, a "don't eat me" marker that inhibits the key efferocytosis driver, MER tyrosine kinase (MERTK), thus blocking the clearance of damaged cells [240][241][242][243]. The recently designed CD47 inhibitors, including Hu5F9 and TTI-621, facilitate efferocytosis by blocking the expression of "do not eat me" signals, [244].…”

Section: Negative Efferocytosis Regulator Blockersmentioning

confidence: 99%

Long COVID and the Neuroendocrinology of Microbial Translocation Outside the GI Tract: Some Treatment Strategies

Sfera

Osorio

Hazan³

et al. 2022

Endocrines

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Similar to previous pandemics, COVID-19 has been succeeded by well-documented post-infectious sequelae, including chronic fatigue, cough, shortness of breath, myalgia, and concentration difficulties, which may last 5 to 12 weeks or longer after the acute phase of illness. Both the psychological stress of SARS-CoV-2 infection and being diagnosed with COVID-19 can upregulate cortisol, a stress hormone that disrupts the efferocytosis effectors, macrophages, and natural killer cells, leading to the excessive accumulation of senescent cells and disruption of biological barriers. This has been well-established in cancer patients who often experience unrelenting fatigue as well as gut and blood–brain barrier dysfunction upon treatment with senescence-inducing radiation or chemotherapy. In our previous research from 2020 and 2021, we linked COVID-19 to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) via angiotensin II upregulation, premature endothelial senescence, intestinal barrier dysfunction, and microbial translocation from the gastrointestinal tract into the systemic circulation. In 2021 and 2022, these hypotheses were validated and SARS-CoV-2-induced cellular senescence as well as microbial translocation were documented in both acute SARS-CoV-2 infection, long COVID, and ME/CFS, connecting intestinal barrier dysfunction to disabling fatigue and specific infectious events. The purpose of this narrative review is to summarize what is currently known about host immune responses to translocated gut microbes and how these responses relate to fatiguing illnesses, including long COVID. To accomplish this goal, we examine the role of intestinal and blood–brain barriers in long COVID and other illnesses typified by chronic fatigue, with a special emphasis on commensal microbes functioning as viral reservoirs. Furthermore, we discuss the role of SARS-CoV-2/Mycoplasma coinfection in dysfunctional efferocytosis, emphasizing some potential novel treatment strategies, including the use of senotherapeutic drugs, HMGB1 inhibitors, Toll-like receptor 4 (TLR4) blockers, and membrane lipid replacement.

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Design, synthesis and biological evaluations of niclosamide analogues against SARS-CoV-2

Cited by 13 publications

References 23 publications

Small molecules in the treatment of COVID-19

Small molecules in the treatment of COVID-19

Recent updates on the biological efficacy of approved drugs and potent synthetic compounds against SARS-CoV-2

Long COVID and the Neuroendocrinology of Microbial Translocation Outside the GI Tract: Some Treatment Strategies

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