Targeting the vital non-structural proteins (NSP12, NSP7, NSP8 and NSP3) from SARS-CoV-2 and inhibition of RNA polymerase by natural bioactive compound naringenin as a promising drug candidate against COVID-19

Aleebrahim-Dehkordi, Elahe; Ghoshouni, Hamed; Koochaki, Pooneh; Esmaili-Dehkordi, Mohsen; Aleebrahim, Elham; Chichagi, Fatemeh; Jafari, Ali; Hanaei, Sara; Heidari-Soureshjani, Ehsan; Rezaei, Nima

doi:10.1016/j.molstruc.2023.135642

Cited by 7 publications

(2 citation statements)

References 65 publications

(75 reference statements)

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“…It has a critical role in counteracting host innate immunity as well, due to its de-ADP-ribosylating, de-ubiquitinating, and de-ISGylating activities [31]. Accordingly, it is a target of antiviral drugs, such as remdesivir [31][32][33][34]. Given that the subject I_4 was treated with remdesivir, an antiviral that has previously been suggested to foster viral evolution [8,9,15,34], the treatment might have promoted the emergence of such mutation.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Intra-host Evolution Is Not Favoured by Immune System Deficiencies

Manuto,

Bado,

Cola

et al. 2023

Preprint

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During the COVID-19 pandemic, immunosuppressed patients showed prolonged SARS-CoV-2 infections, with several studies reporting the accumulation of mutations in the viral genome. The weakened immune system present in these individuals, along with the effect of antiviral thera-pies, are thought to create a favourable environment for intra-host viral evolution and have been linked to the emergence of new viral variants, which strongly challenged the containment measures and some therapeutic treatments. To assess whether an impaired immunity could lead to an increased instability of viral genomes, longitudinal nasopharyngeal swabs were collected from eight immunocompromised patients and fourteen non-immunocompromised subjects, all undergoing SARS-CoV-2 infection. Intra-host viral evolution was compared between the two groups through deep sequencing, exploiting a probe-based enrichment method to minimize the possibility of artefactual mutations commonly generated in amplicon-based methods, which heavily rely on PCR amplification. Although, as expected, immunocompromised patients expe-rienced significantly longer infections, the acquisition of novel intra-host viral mutations was similar between the two groups. Moreover, a thorough analysis of viral quasispecies showed that the variability of viral populations in the two groups is comparable not only at the consensus level, but also when considering low frequency mutations. This study suggests that a compro-mised immune system alone does not affect SARS-CoV-2 within-host genomic variability.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Intra-host Evolution Is Not Favoured by Immune System Deficiencies

Manuto,

Bado,

Cola

et al. 2023

Preprint

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“…Moreover, numerous molecular docking studies reveal that naringenin binds to viral spiking proteins, viral major proteases, host receptors, and host viral transport channels and has multiple antiviral effects against SARS-CoV-2 [ 47 ]. For instance, naringenin can influence the replication of the viral genome by attaching to SARS-CoV-2 macrodomain RNA polymerase (NSP3), SARS-CoV-2 RNA-dependent RNA polymerase (NSP12), and 3-chymotrypsin-like protease, as well as affect viral invasion by attaching to the ACE2 receptor to achieve an antiviral effect [ 48 , 49 ]. However, despite the abundance of evidence suggesting that naringin and naringenin can be more effective in treating various illnesses, there is yet to be a review of their combined potential in treating multiple coexisting conditions of long COVID.…”

Section: Introductionmentioning

confidence: 99%

Potential Beneficial Effects of Naringin and Naringenin on Long COVID—A Review of the Literature

Liu,

Zhong,

et al. 2024

Microorganisms

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Coronavirus disease 2019 (COVID-19) caused a severe epidemic due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent studies have found that patients do not completely recover from acute infections, but instead, suffer from a variety of post-acute sequelae of SARS-CoV-2 infection, known as long COVID. The effects of long COVID can be far-reaching, with a duration of up to six months and a range of symptoms such as cognitive dysfunction, immune dysregulation, microbiota dysbiosis, myalgic encephalomyelitis/chronic fatigue syndrome, myocarditis, pulmonary fibrosis, cough, diabetes, pain, reproductive dysfunction, and thrombus formation. However, recent studies have shown that naringenin and naringin have palliative effects on various COVID-19 sequelae. Flavonoids such as naringin and naringenin, commonly found in fruits and vegetables, have various positive effects, including reducing inflammation, preventing viral infections, and providing antioxidants. This article discusses the molecular mechanisms and clinical effects of naringin and naringenin on treating the above diseases. It proposes them as potential drugs for the treatment of long COVID, and it can be inferred that naringin and naringenin exhibit potential as extended long COVID medications, in the future likely serving as nutraceuticals or clinical supplements for the comprehensive alleviation of the various manifestations of COVID-19 complications.

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