COVID-19 and Senotherapeutics: Any Role for the Naturally-occurring Dipeptide Carnosine?

Hipkiss, Alan R.

doi:10.14336/ad.2020.0518

Cited by 13 publications

(12 citation statements)

References 59 publications

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“…PubMed search strategy yielded only three publications with commentaries on using carnosine and salicyl-carnosine, suggested for patients with COVID-19 [37][38][39]. In these papers, carnosine and salicyl-carnosine have been repurposed based on mere clinical and/or laboratory grounds.…”

Section: Literature Evaluationmentioning

confidence: 99%

Carnosine to Combat Novel Coronavirus (nCoV): Molecular Docking and Modeling to Cocrystallized Host Angiotensin-Converting Enzyme 2 (ACE2) and Viral Spike Protein

et al. 2020

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Aims: Angiotensin-converting enzyme 2 (ACE2) plays an important role in the entry of coronaviruses into host cells. The current paper described how carnosine, a naturally occurring supplement, can be an effective drug candidate for coronavirus disease (COVID-19) on the basis of molecular docking and modeling to host ACE2 cocrystallized with nCoV spike protein. Methods: First, the starting point was ACE2 inhibitors and their structure–activity relationship (SAR). Next, chemical similarity (or diversity) and PubMed searches made it possible to repurpose and assess approved or experimental drugs for COVID-19. Parallel, at all stages, the authors performed bioactivity scoring to assess potential repurposed inhibitors at ACE2. Finally, investigators performed molecular docking and modeling of the identified drug candidate to host ACE2 with nCoV spike protein. Results: Carnosine emerged as the best-known drug candidate to match ACE2 inhibitor structure. Preliminary docking was more optimal to ACE2 than the known typical angiotensin-converting enzyme 1 (ACE1) inhibitor (enalapril) and quite comparable to known or presumed ACE2 inhibitors. Viral spike protein elements binding to ACE2 were retained in the best carnosine pose in SwissDock at 1.75 Angstroms. Out of the three main areas of attachment expected to the protein–protein structure, carnosine bound with higher affinity to two compared to the known ACE2 active site. LibDock score was 92.40 for site 3, 90.88 for site 1, and inside the active site 85.49. Conclusion: Carnosine has promising inhibitory interactions with host ACE2 and nCoV spike protein and hence could offer a potential mitigating effect against the current COVID-19 pandemic.

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Section: Literature Evaluationmentioning

confidence: 99%

Carnosine to Combat Novel Coronavirus (nCoV): Molecular Docking and Modeling to Cocrystallized Host Angiotensin-Converting Enzyme 2 (ACE2) and Viral Spike Protein

et al. 2020

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“…Severe cases of COVID-19 are associated with multi-organ damage arising from oxidative stress (21), raising the possibility of global depletion of carnosine in these patients and underscoring its therapeutic potential (22). Recently, Kulikova and colleagues (23) developed an analogue of carnosine, salicyl-carnosine, designed to circumvent the rapid degradation by serum carosinase.…”

Section: Discussionmentioning

confidence: 99%

Small-molecule metabolome identifies potential therapeutic targets against COVID-19

Bennet

Kaufmann

Takami

et al. 2021

Preprint

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Background: Respiratory viruses are transmitted and acquired via the nasal mucosa, and thereby may influence the nasal metabolome composed of biochemical products produced by both host cells and microbes. Studies of the nasal metabolome demonstrate virus-specific changes that sometimes correlate with viral load and disease severity. Here, we evaluate the nasopharyngeal metabolome of COVID-19 infected individuals and report several small molecules that may be used as potential therapeutic targets. Specimens were tested by qRT-PCR with target primers for three viruses: Influenza A (INFA), respiratory syncytial virus (RSV), and SARS-CoV-2, along with asymptomatic controls. The nasopharyngeal metabolome was characterized using an LC-MS/MS-based small-molecule screening kit capable of quantifying 141 analytes. A machine learning model identified 28 discriminating analytes and correctly categorized patients with a viral infection with an accuracy of 96% (R2=0.771, Q2=0.72). A second model identified 5 analytes to differentiate COVID19-infected patients from those with INFA or RSV with an accuracy of 85% (R2=0.442, Q2=0.301). Specifically, LysoPCaC18:2 concentration was significantly increased in COVID19 patients (P< 0.0001), whereas beta-hydroxybutyric acid, Met SO, succinic acid, and carnosine concentrations were significantly decreased (P< 0.0001). This study demonstrates that COVID19 infection results in a unique NP metabolomic signature with carnosine and LysoPCaC18:2 as potential therapeutic targets.

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“…It is possible that carnosine could exert protective activity towards Covid-19 infection and subsequent pathology. 60,61 Not only does the dipeptide suppress some of the metabolic changes consequent upon viral infection, it may actually inhibit viral entry too. 36 Given that the virus enters the lungs, it is possible that raising the olfactory level of carnosine via nasal administration could be an effective strategy first to inhibit viral entry and then raise carnosine levels in the CNS generally, which may protect against glycation-induced dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Covid-19, Carnosine and Cognition

Hipkiss¹

2021

SOJNN

Self Cite

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The possible ameliorative roles of the dipeptide carnosine with respect to Covid-19 viral infection and associated pathologies are discussed. In particular carnosine’s ability to suppress age-related changes in carbohydrate metabolism which normally exacerbate Covid-19-induced dysfunction as well as the dipeptide’s anti-inflammatory activity is considered. As carnosine is normally present in the olfactory lobe and that anosmia (loss of sense of smell) is a common feature of Covid-19’s effect on humans, the possibility that nasal administration of carnosine could be therapeutic is considered as a means of raising levels of the dipeptide in the olfactory lobe and thereby alleviates virus-mediated neuropathology.

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COVID-19 and Senotherapeutics: Any Role for the Naturally-occurring Dipeptide Carnosine?

Cited by 13 publications

References 59 publications

Carnosine to Combat Novel Coronavirus (nCoV): Molecular Docking and Modeling to Cocrystallized Host Angiotensin-Converting Enzyme 2 (ACE2) and Viral Spike Protein

Carnosine to Combat Novel Coronavirus (nCoV): Molecular Docking and Modeling to Cocrystallized Host Angiotensin-Converting Enzyme 2 (ACE2) and Viral Spike Protein

Small-molecule metabolome identifies potential therapeutic targets against COVID-19

Covid-19, Carnosine and Cognition

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