Drugs for COVID-19 Treatment: A New Challenge

Talukder, Pratik; Saha, Arunima; Roy, Sohini; Ghosh, Gargi; Roy, Debshikha Dutta; Barua, Snejuti

doi:10.1007/s12010-023-04439-4

Cited by 4 publications

(2 citation statements)

References 91 publications

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“…Cellular uptake of LDL- and HDL-derived cholesterol rapidly influences cholesterol levels at the plasma membrane and endocytic vesicles including LE/Lys, and dyslipidemia has been implicated to support SARS-CoV-2 infection by altering membrane lipid composition and interfering with immune cell function ( Makhoul et al, 2022 ). Importantly, cell surface binding, cellular uptake, and propagation of SARS-CoV-2 are intimately linked to cellular cholesterol metabolism and distribution, providing therapeutic opportunities ( Wang et al, 2022 ; Talukder et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Cholesterol and COVID-19—therapeutic opportunities at the host/virus interface during cell entry

Grewal,

Nguyen,

Buechler

2024

Life Sci. Alliance

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The rapid development of vaccines to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has been critical to reduce the severity of COVID-19. However, the continuous emergence of new SARS-CoV-2 subtypes highlights the need to develop additional approaches that oppose viral infections. Targeting host factors that support virus entry, replication, and propagation provide opportunities to lower SARS-CoV-2 infection rates and improve COVID-19 outcome. This includes cellular cholesterol, which is critical for viral spike proteins to capture the host machinery for SARS-CoV-2 cell entry. Once endocytosed, exit of SARS-CoV-2 from the late endosomal/lysosomal compartment occurs in a cholesterol-sensitive manner. In addition, effective release of new viral particles also requires cholesterol. Hence, cholesterol-lowering statins, proprotein convertase subtilisin/kexin type 9 antibodies, and ezetimibe have revealed potential to protect against COVID-19. In addition, pharmacological inhibition of cholesterol exiting late endosomes/lysosomes identified drug candidates, including antifungals, to block SARS-CoV-2 infection. This review describes the multiple roles of cholesterol at the cell surface and endolysosomes for SARS-CoV-2 entry and the potential of drugs targeting cholesterol homeostasis to reduce SARS-CoV-2 infectivity and COVID-19 disease severity.

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Section: Introductionmentioning

confidence: 99%

Cholesterol and COVID-19—therapeutic opportunities at the host/virus interface during cell entry

Grewal,

Nguyen,

Buechler

2024

Life Sci. Alliance

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“…13 Other compounds are undergoing clinical testing, and novel intervention approaches are being assessed. 14,15 Currently, there is considerable interest in the possible use of extracellular vesicles (EVs) or their subcomponents as a means of preventing or treating medical conditions. 16 EVs are nanoparticles produced by all cell types and contain soluble molecules, such as proteins and nucleic acids including microRNA (miRNA) and messenger RNAs (mRNAs).…”

Section: Introductionmentioning

confidence: 99%

Exosomes, and the potential for exosome‐based interventions against COVID‐19

Rahmani,

Soleymani,

Almukhtar

et al. 2024

Reviews in Medical Virology

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Since late 2019, the world has been devastated by the coronavirus disease 2019 (COVID‐19) induced by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), with more than 760 million people affected and ∼seven million deaths reported. Although effective treatments for COVID‐19 are currently limited, there has been a strong focus on developing new therapeutic approaches to address the morbidity and mortality linked to this disease. An approach that is currently being investigated is the use of exosome‐based therapies. Exosomes are small, extracellular vesicles that play a role in many clinical diseases, including viral infections, infected cells release exosomes that can transmit viral components, such as miRNAs and proteins, and can also include receptors for viruses that facilitate viral entry into recipient cells. SARS‐CoV‐2 has the ability to impact the formation, secretion, and release of exosomes, thereby potentially facilitating or intensifying the transmission of the virus among cells, tissues and individuals. Therefore, designing synthetic exosomes that carry immunomodulatory cargo and antiviral compounds are proposed to be a promising strategy for the treatment of COVID‐19 and other viral diseases. Moreover, exosomes generated from mesenchymal stem cells (MSC) might be employed as cell‐free therapeutic agents, as MSC‐derived exosomes can diminish the cytokine storm and reverse the suppression of host anti‐viral defences associated with COVID‐19, and boost the repair of lung damage linked to mitochondrial activity. The present article discusses the significance and roles of exosomes in COVID‐19, and explores potential future applications of exosomes in combating this disease. Despite the challenges posed by COVID‐19, exosome‐based therapies could represent a promising avenue for improving patient outcomes and reducing the impact of this disease.

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Development of potent pan‐coronavirus fusion inhibitors with a new design strategy

Zhu,

Gao,

Feng

et al. 2024

MedComm

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Development of potent and broad‐spectrum drugs against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) remains one of the top priorities, especially in the cases of the emergence of mutant viruses and inability of current vaccines to prevent viral transmission. In this study, we have generated a novel membrane fusion‐inhibitory lipopeptide IPB29, which is currently under clinical trials; herein, we report its design strategy and preclinical data. First, we surprisingly found that IPB29 with a rigid linker between the peptide sequence and lipid molecule had greatly improved α‐helical structure and antiviral activity. Second, IPB29 potently inhibited a large panel of SARS‐CoV‐2 variants including the previously and currently circulating viruses, such as Omicron XBB.5.1 and EG.5.1. Third, IPB29 could also cross‐neutralize the bat‐ and pangolin‐isolated SARS‐CoV‐2‐related CoVs (RatG13, PCoV‐GD, and PCoV‐GX) and other human CoVs (SARS‐CoV, MERS‐CoV, HCoV‐NL63, and HCoV‐229E). Fourth, IPB29 administrated as an inhalation solution (IPB29‐IS) in Syrian hamsters exhibited high therapeutic and preventive efficacies against SARS‐CoV‐2 Delta or Omicron variant. Fifth, the pharmacokinetic profiles and safety pharmacology of IPB29‐IS were extensively characterized, providing data to support its evaluation in humans. In conclusion, our studies have demonstrated a novel design strategy for viral fusion inhibitors and offered an ideal drug candidate against SARS‐CoV‐2 and other coronaviruses.

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Drugs for COVID-19 Treatment: A New Challenge

Cited by 4 publications

References 91 publications

Cholesterol and COVID-19—therapeutic opportunities at the host/virus interface during cell entry

Cholesterol and COVID-19—therapeutic opportunities at the host/virus interface during cell entry

Exosomes, and the potential for exosome‐based interventions against COVID‐19

Development of potent pan‐coronavirus fusion inhibitors with a new design strategy

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