COVID-19: molecular targets, drug repurposing and new avenues for drug discovery

Senger, Mário Roberto; Evangelista, Tereza Cristina Santos; Dantas, Rafael Ferreira; Santana, Marcos Vinicius da Silva; Gonçalves, Luiz Carlos Saramago; Neto, Lauro Ribeiro de Souza; Ferreira, Sabrina Baptista; Silva, Floriano Paes

doi:10.1590/0074-02760200254

Cited by 33 publications

(42 citation statements)

References 240 publications

(571 reference statements)

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“…The molecular targets of SARS-CoV-2 include various viral proteins involved in viral entry, such as spike proteins, and replication, such as viral proteases. 122 In addition, host cell targets, such as angiotensin-converting enzyme 2 (ACE2) receptor and cell surface heat shock protein (HSPA5), which are involved in viral entry, may also offer potential therapeutic targets. 122 Molecular docking studies have already shown that TQ could potentially inhibit COVID-19 by binding to the receptor-binding domain on the spike protein of SARS-CoV-2, which would hinder virus entry into the host cell.…”

Section: Potential Beneficial Effects Of Thymoquinone In Covid-19mentioning

confidence: 99%

“… 122 In addition, host cell targets, such as angiotensin-converting enzyme 2 (ACE2) receptor and cell surface heat shock protein (HSPA5), which are involved in viral entry, may also offer potential therapeutic targets. 122 Molecular docking studies have already shown that TQ could potentially inhibit COVID-19 by binding to the receptor-binding domain on the spike protein of SARS-CoV-2, which would hinder virus entry into the host cell. 123 Additionally, it may bind to the SARS-CoV-2 envelope protein and inhibit its ion channel and pore formation activity.…”

Section: Potential Beneficial Effects Of Thymoquinone In Covid-19mentioning

confidence: 99%

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Thymoquinone: A Promising Natural Compound with Potential Benefits for COVID-19 Prevention and Cure

Badary¹,

Hamza²,

Tikamdas³

2021

DDDT

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Section: Potential Beneficial Effects Of Thymoquinone In Covid-19mentioning

confidence: 99%

Section: Potential Beneficial Effects Of Thymoquinone In Covid-19mentioning

confidence: 99%

Thymoquinone: A Promising Natural Compound with Potential Benefits for COVID-19 Prevention and Cure

Badary¹,

Hamza²,

Tikamdas³

2021

DDDT

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“…thapsigargin) ( Al-Beltagi et al., 2021 ) and autophagy (e.g. hydroxichloroquine) ( Senger et al., 2020 ) were shown to be broad-spectrum inhibitors for several respiratory viruses, including CoV, and emerged as candidates. Even though experimental findings have not yet been translated into efficient treatment and the use of these drugs remains controversial, the literature offers a rationale to target UPR and autophagy in the context of CoV infections.…”

Section: Manipulation Of Upr and Autophagy As A Strategy To Limit Cov Replicationmentioning

confidence: 99%

“…One of the first proposed clinical trials in the wake of the COVID-19 pandemic draw huge worldwide attention to the putative benefits of hydroxychloroquine (HCQ) in the early treatment of patients infected with SARS-CoV-2 ( Senger et al., 2020 ). Previously, HCQ had been shown to inhibit MERS-CoV replication in vitro in a screening of FDA-approved compound library ( Touret et al., 2020 ).…”

Section: Manipulation Of Upr and Autophagy As A Strategy To Limit Cov Replicationmentioning

confidence: 99%

The Unfolded Protein Response and Autophagy on the Crossroads of Coronaviruses Infections

Prestes

Bruno

Travassos

et al. 2021

Front. Cell. Infect. Microbiol.

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The ability to sense and adequately respond to variable environmental conditions is central for cellular and organismal homeostasis. Eukaryotic cells are equipped with highly conserved stress-response mechanisms that support cellular function when homeostasis is compromised, promoting survival. Two such mechanisms – the unfolded protein response (UPR) and autophagy – are involved in the cellular response to perturbations in the endoplasmic reticulum, in calcium homeostasis, in cellular energy or redox status. Each of them operates through conserved signaling pathways to promote cellular adaptations that include re-programming transcription of genes and translation of new proteins and degradation of cellular components. In addition to their specific functions, it is becoming increasingly clear that these pathways intersect in many ways in different contexts of cellular stress. Viral infections are a major cause of cellular stress as many cellular functions are coopted to support viral replication. Both UPR and autophagy are induced upon infection with many different viruses with varying outcomes – in some instances controlling infection while in others supporting viral replication and infection. The role of UPR and autophagy in response to coronavirus infection has been a matter of debate in the last decade. It has been suggested that CoV exploit components of autophagy machinery and UPR to generate double-membrane vesicles where it establishes its replicative niche and to control the balance between cell death and survival during infection. Even though the molecular mechanisms are not fully elucidated, it is clear that UPR and autophagy are intimately associated during CoV infections. The current SARS-CoV-2 pandemic has brought renewed interest to this topic as several drugs known to modulate autophagy – including chloroquine, niclosamide, valinomycin, and spermine – were proposed as therapeutic options. Their efficacy is still debatable, highlighting the need to better understand the molecular interactions between CoV, UPR and autophagy.

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“…(2,3,4) The transmission can occur via contaminated nasal/oral respiratory droplets and surfaces. (5) Molecular biology approaches are the standard methods to detect coronavirus. The most reliable and widely used COVID-19 diagnostic test is the reverse-transcriptase polymerase chain reaction (RT-PCR).…”

mentioning

confidence: 99%

Comparison of viral load between saliva and nasopharyngeal swabs for SARS-CoV2: the role of days of symptoms onset on diagnosis

Justo

Bueno

Barbosa

et al. 2021

Mem. Inst. Oswaldo Cruz

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BACKGROUND Coronavirus disease 2019 (COVID-19) is highly infectious causing millions of deaths worldwide. Nasopharyngeal swabs are the primary sample of choice for the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thus, to decrease the exposure to potentially infected samples through the collection is a key point to reduce the risk of infection in healthcare workers.OBJECTIVES This study aimed to evaluate the sensitivity and viral load of saliva specimens by days of symptoms onset comparing to nasopharyngeal swabs in subjects with mild symptoms.METHODS Saliva and nasopharyngeal swabs samples were collected from São Paulo Hospital workers presenting mild symptoms, such as fever, cough, sore throat, rhinorrhea, myalgia, headaches, anosmia, ageusia, and fatigue. To understand the positivity and viral load, reverse transcription-polymerase chain reaction (RT-PCR) was performed.FINDINGS Saliva specimens presented a sensitivity of 98.6% compared to nasopharyngeal swabs. Overall, saliva showed lower viral load compared to nasopharyngeal swabs, regarding days of symptoms onset on diagnosis, the first four days had significant changes in viral load and no significant difference was reported in the days five to nine.MAIN CONCLUSIONS Although RT-PCR of saliva has presented a lower viral load compared to nasopharyngeal swabs, saliva specimens are a potential and reliable candidate for COVID-19 diagnosis through RT-PCR.

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COVID-19: molecular targets, drug repurposing and new avenues for drug discovery

Cited by 33 publications

References 240 publications

Thymoquinone: A Promising Natural Compound with Potential Benefits for COVID-19 Prevention and Cure

Thymoquinone: A Promising Natural Compound with Potential Benefits for COVID-19 Prevention and Cure

The Unfolded Protein Response and Autophagy on the Crossroads of Coronaviruses Infections

Comparison of viral load between saliva and nasopharyngeal swabs for SARS-CoV2: the role of days of symptoms onset on diagnosis

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