Impairment of SARS-CoV-2 spike glycoprotein maturation and fusion activity by nitazoxanide: an effect independent of spike variants emergence

Riccio, Anna; Santopolo, Silvia; Rossi, Antônio; Piacentini, Sara; Rossignol, Jean‐François; Mg, Santoro

doi:10.1007/s00018-022-04246-w

Cited by 26 publications

(33 citation statements)

References 89 publications

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“…Another intriguing hypothesis to be considered is that, due to the high cell–cell fusion activity of its spike protein [ 102 , 103 ], the SARS-CoV-2 virion or some of the virus components may spread through cell–cell contact. This insidious strategy, which is adopted by other RNA viruses, including the respiratory syncytial virus, the measles virus [ 104 ] and the human immunodeficiency virus [ 105 ], allows the pathogen to spread in a particle-independent way, promoting immune evasion [ 106 ].…”

Section: Mechanisms Of Pathogenesis: Virus Persistencementioning

confidence: 99%

Long Covid: where we stand and challenges ahead

et al. 2022

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Post-acute sequelae of SARS-CoV-2 (PASC), also known as Post-Covid Syndrome, and colloquially as Long Covid, has been defined as a constellation of signs and symptoms which persist for weeks or months after the initial SARS-CoV-2 infection. PASC affects a wide range of diverse organs and systems, with manifestations involving lungs, brain, the cardiovascular system and other organs such as kidney and the neuromuscular system. The pathogenesis of PASC is complex and multifactorial. Evidence suggests that seeding and persistence of SARS-CoV-2 in different organs, reactivation, and response to unrelated viruses such as EBV, autoimmunity, and uncontrolled inflammation are major drivers of PASC. The relative importance of pathogenetic pathways may differ in different tissue and organ contexts. Evidence suggests that vaccination, in addition to protecting against disease, reduces PASC after breakthrough infection although its actual impact remains to be defined. PASC represents a formidable challenge for health care systems and dissecting pathogenetic mechanisms may pave the way to targeted preventive and therapeutic approaches.

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Section: Mechanisms Of Pathogenesis: Virus Persistencementioning

confidence: 99%

Long Covid: where we stand and challenges ahead

et al. 2022

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“… 485 Riccio et al demonstrated that nitazoxanide could hamper the glycosylation of SARS-CoV-2 S protein, thus hindering infectivity of the virus. 486 This study also revealed that nitazoxanide is equally effective against different variants of SARS-CoV-2, including the Delta variant. According to a preprint provided by Miorin et al, nitazoxanide exhibited an IC 50 of 4.04 μM in Vero E6 cells against SARS-CoV-2, and a significant inhibitory effect was observed in different human cell lines including stem cell-derived human alveolar epithelial type 2 cells.…”

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

confidence: 65%

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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“…The direct anti-SARS-CoV-2 effect of NTZ was not confirmed, though a recent study revealed that NTZ may interfere with N -glycosylation of SARS-CoV-2 spike protein [ 60 ]. Likewise, Riccio et al [ 61 ] observed that NTZ blocks the maturation of SARS-CoV-2 spike protein and fusion activity with ACE2 with an effect independent of emergence spike variants (Riccio et al, 2022). Therefore, NTZ might be an effective agent used in the prophylaxis and treatment of mild to severe SARS-CoV-2 infection including the variant strains.…”

Section: Immunological Effects Of Ntz In Covid-19mentioning

confidence: 99%

Nitazoxanide and COVID-19: A review

et al. 2022

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Coronavirus disease 2019 (COVID-19) is a current global illness triggered by severe acute respiratory coronavirus 2 (SARS-CoV-2) leading to acute viral pneumonia, acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and cytokine storm in severe cases. In the COVID-19 era, different unexpected old drugs are repurposed to find out effective and cheap therapies against SARS-CoV-2. One of these elected drugs is nitazoxanide (NTZ) which is an anti-parasitic drug with potent antiviral activity. It is effectively used in the treatment of protozoa and various types of helminths in addition to various viral infections. Thus, we aimed to elucidate the probable effect of NTZ on SARS-CoV-2 infections. Findings of the present study illustrated that NTZ can reduce SARS-CoV-2-induced inflammatory reactions through activation of interferon (IFN), restoration of innate immunity, inhibition of the release of pro-inflammatory cytokines, suppression of the mammalian target of rapamycin (mTOR), and induction of autophagic cell death. Moreover, it can inhibit the induction of oxidative stress which causes cytokine storm and is associated with ALI, ARDS, and multi-organ damage (MOD). This study concluded that NTZ has important anti-inflammatory and immunological properties that may mitigate SARS-CoV-2 infection-induced inflammatory disorders. Despite broad-spectrum antiviral properties of NTZ, the direct anti-SARS-CoV-2 effect was not evident and documented in recent studies. Then, in silico and in vitro studies in addition to clinical trials and prospective studies are needed to confirm the beneficial impact of NTZ on the pathogenesis of SARS-CoV-2 infection. Supplementary Information The online version contains supplementary material available at 10.1007/s11033-022-07822-2.

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Impairment of SARS-CoV-2 spike glycoprotein maturation and fusion activity by nitazoxanide: an effect independent of spike variants emergence

Cited by 26 publications

References 89 publications

Long Covid: where we stand and challenges ahead

Long Covid: where we stand and challenges ahead

Small molecules in the treatment of COVID-19

Nitazoxanide and COVID-19: A review

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