Metadichol®, a Novel Nano Lipid Formulation that Inhibits SARS-COV-2 and a Multitude of Pathological Viruses in vitro

Raghavan, P.R.

doi:10.21203/rs.3.rs-34021/v6

Cited by 3 publications

(3 citation statements)

References 21 publications

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“…Metadichol modulates cytokine storms, as it is an inhibitor of TNF, ICAM1, and CCL2 that play a key role in generating cytokine storms. Metadichol also regulates COVID-19-associated comorbidities [ 86 , 87 ], such as hypertension and diabetes [ 88 – 90 ]. Thus, Metadichol has the potential to improve the long-term prognosis of the affected patient population.…”

Section: Discussionmentioning

confidence: 99%

Metadichol®: A Novel Nanolipid Formulation That Inhibits SARS-CoV-2 and a Multitude of Pathological Viruses In Vitro

Raghavan¹

2022

BioMed Research International

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Increasing outbreaks of new pathogenic viruses have promoted the exploration of novel alternatives to time-consuming vaccines. Thus, it is necessary to develop a universal approach to halt the spread of new and unknown viruses as they are discovered. One such promising approach is to target lipid membranes, which are common to all viruses and bacteria. The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has reaffirmed the importance of interactions between the virus envelope and the host cell plasma membrane as a critical mechanism of infection. Metadichol®, a nanolipid emulsion of long-chain alcohols, has been demonstrated as a strong candidate that inhibits the proliferation of SARS-CoV-2. Naturally derived substances, such as long-chain saturated lipid alcohols, reduce viral infectivity, including that of coronaviruses (such as SARS-CoV-2) by modifying their lipid-dependent attachment mechanism to human host cells. The receptor ACE2 mediates the entry of SARS-CoV-2 into the host cells, whereas the serine protease TMPRSS2 primes the viral S protein. In this study, Metadichol® was found to be 270 times more potent an inhibitor of TMPRSS2 ( E C 50 = 96 ng / mL ) than camostat mesylate ( E C 50 = 26000 ng / mL ). Additionally, it inhibits ACE with an EC50 of 71 ng/mL, but it is a very weak inhibitor of ACE2 at an EC50 of 31 μg/mL. Furthermore, the live viral assay performed in Caco-2 cells revealed that Metadichol® inhibits SARS-CoV-2 replication at an EC90 of 0.16 μg/mL. Moreover, Metadichol® had an EC90 of 0.00037 μM, making it 2081 and 3371 times more potent than remdesivir ( E C 50 = 0.77 μ M ) and chloroquine ( E C 50 = 1.14 μ M ), respectively.

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Section: Discussionmentioning

confidence: 99%

Metadichol®: A Novel Nanolipid Formulation That Inhibits SARS-CoV-2 and a Multitude of Pathological Viruses In Vitro

Raghavan¹

2022

BioMed Research International

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“… 80 Raghavan et al suggested that metadichol can inhibit the ACE2 enzyme. 81 Molecular dynamics studies and binding enthalpy calculations suggest that the binding enthalpy could be reduced for the S protein–ACE2 interface in the presence of the MLN-4760 inhibitor. 82 This weakening of binding strength was proposed as a result of the destabilization of the interactions between ACE2 and RBD.…”

Section: Introductionmentioning

confidence: 99%

“…designed a sequence of a few amino acids and functionalized with gold nanoparticles as antivirals to prevent the viral entry . Raghavan et al suggested that metadichol can inhibit the ACE2 enzyme . Molecular dynamics studies and binding enthalpy calculations suggest that the binding enthalpy could be reduced for the S protein–ACE2 interface in the presence of the MLN-4760 inhibitor .…”

Section: Introductionmentioning

confidence: 99%

Effect of an Inhibitor on the ACE2-Receptor-Binding Domain of SARS-CoV-2

Sharma

Song

Merz

2022

J. Chem. Inf. Model.

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The recent outbreak of COVID-19 infection started in Wuhan, China, and spread across China and beyond. Since the WHO declared COVID-19 a pandemic (March 11, 2020), three vaccines and only one antiviral drug (remdesivir) have been approved (Oct 22, 2020) by the FDA. The coronavirus enters human epithelial cells by the binding of the densely glycosylated fusion spike protein (S protein) to a receptor (angiotensin-converting enzyme 2, ACE2) on the host cell surface. Therefore, inhibiting the viral entry is a promising treatment pathway for preventing or ameliorating the effects of COVID-19 infection. In the current work, we have used all-atom molecular dynamics (MD) simulations to investigate the influence of the MLN-4760 inhibitor on the conformational properties of ACE2 and its interaction with the receptor-binding domain (RBD) of SARS-CoV-2. We have found that the presence of an inhibitor tends to completely/partially open the ACE2 receptor where the two subdomains (I and II) move away from each other, while the absence results in partial or complete closure. The current study increases our understanding of ACE inhibition by MLN-4760 and how it modulates the conformational properties of ACE2.

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Therapeutic Antiaging Strategies

Mishra

Balendra²,

Esposto

et al. 2022

Biomedicines

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Aging constitutes progressive physiological changes in an organism. These changes alter the normal biological functions, such as the ability to manage metabolic stress, and eventually lead to cellular senescence. The process itself is characterized by nine hallmarks: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. These hallmarks are risk factors for pathologies, such as cardiovascular diseases, neurodegenerative diseases, and cancer. Emerging evidence has been focused on examining the genetic pathways and biological processes in organisms surrounding these nine hallmarks. From here, the therapeutic approaches can be addressed in hopes of slowing the progression of aging. In this review, data have been collected on the hallmarks and their relative contributions to aging and supplemented with in vitro and in vivo antiaging research experiments. It is the intention of this article to highlight the most important antiaging strategies that researchers have proposed, including preventive measures, systemic therapeutic agents, and invasive procedures, that will promote healthy aging and increase human life expectancy with decreased side effects.

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Metadichol®, a Novel Nano Lipid Formulation that Inhibits SARS-COV-2 and a Multitude of Pathological Viruses in vitro

Cited by 3 publications

References 21 publications

Metadichol®: A Novel Nanolipid Formulation That Inhibits SARS-CoV-2 and a Multitude of Pathological Viruses In Vitro

Metadichol®: A Novel Nanolipid Formulation That Inhibits SARS-CoV-2 and a Multitude of Pathological Viruses In Vitro

Effect of an Inhibitor on the ACE2-Receptor-Binding Domain of SARS-CoV-2

Therapeutic Antiaging Strategies

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