A new answer to treating the new coronavirus quantum biology

The novel coronavirus SARS-CoV-2 (disease name COVID-19) has fundamentally changed the world we live in: while the development of a SARS-CoV-2 vaccine is indispensable, it is undeniable that we have entered a new era of pandemics. Given the importance of receptor recognition, binding and activation in a biological context, there is an urgent need to review quantum attempt penetration effects in the context of viral invasion mechanisms into the host.

Recently, a South African scientific team reviewed the quantum tunneling effect of SARS-CoV-2 infection and discussed the possible consequences of this linkage in three aspects: host cell invasion, medical intervention and post-viral syndrome.

01Biomolecular recognition: enzymatic function, receptor binding, olfactory symptoms and immune response in neocoronaviruses

Charge transfer is a well-established topic in quantum biology; more specifically, the biological context of such transfer is often a membrane-embedded protein. Scientists are very interested in how the biological context assists the charge transfer process, e.g., through the vibration of protein scaffolds, the vibration of binding ligands. Therefore, it is extremely relevant to consider charge transfer in the context of SARS-CoV-2 virus infection: the virus uses membrane-embedded proteins to invade host cells.

SARS-CoV-2 spike proteins invade host cells by binding to ACE2 receptors embedded in the cell membrane.

Our current understanding of SARS-CoV-2 viruses touches on specific biological examples of tunneling effects: enzymes, receptor binding, and olfaction.

Before a new coronavirus can proliferate it needs to invade its host cell; studies suggest that SARS-CoV-2 viruses are most likely to invade host cells through interactions with host enzymes, specifically angiotensin-converting enzyme (ACE2). The spike protein of the virus, which is also the target of the vaccine, binds to the membrane-embedded ACE2 and facilitates the fusion of the virus and host membrane.

ACE2 is an enzyme that regulates the binding of the ligand angiotensin form of the G protein-coupled receptor (GPCR), a hormone that is part of the renin-angiotensin-aldosterone system (RAAS). In addition to this, angiotensins are important for the balance between vasodilation and vasoconstriction, and they are also integral to cardiovascular function. Although the ACE2 enzyme is the focus of most current studies, other enzymes have also been associated with SARS-CoV-2 virus infection.

For example, the host cell serine protease TMPRSS2 is necessary for protein priming of spike proteins and facilitates viral entry into host cells; histone protease L (cathepsin L), is associated with spike protein cleavage and enhanced viral entry into host cells.

The GPCR itself appears to play a role in diseases associated with SARS-CoV-2 infection. the effect of COVID-19 on olfaction is one of the defining symptoms of the disease, with elevated expression of ACE2 in olfactory epithelial cells, where the olfactory GPCR is also located, which may be responsible for COVID-19-associated anosmia or altered olfaction; the GPCR is important in the COVID-19 s inflammatory response is also important. The increased morbidity is associated with the cytokine storm induced by this virus, which are small proteins produced by immune cells. However, overproduction and dysregulation of cytokines may lead to tissue damage and death. Therefore, cytokines have been suggested as a possible therapeutic target to improve COVID-19 mortality.

Whether quantum effects may play a role in SARS-CoV-2 infection, for example, is debatable. However, molecular recognition and binding in a physiological context is integral to viral infection; as a common factor in enzyme function, receptor binding, olfactory symptoms, and immune response, it deserves closer scrutiny through as many lenses as possible.

02Binding of neocoronavirus spike proteins: modeling the electron transfer process

In specific experiments, scientists modeled the interaction of spike proteins and ACE2 receptors as vibrationally assisted electron transfer.

Using the open open quantum system concept, and borrowing from models developed for olfaction, the team outlined the maximum transfer probability of the ACE2 receptor in relation to its coupling to a single vibrational electron mode associated with the SARS-CoV-2 spike protein, and modeled the receptor as a dimer of.

Simplified modeling of vibrationally assisted tunneling in the context of SARS-CoV-2 infection. The vibrational spectrum of the spike protein matches the conversion energy of electrons in the ACE2 receptor, facilitating electron transfer and receptor activation.

Ultimately, the coupling (γ) between the levels in the dimer (J) is plotted as a range of different values for each vibrational electron frequency: 0.0001, 0.001, 0.01 and 0.1 eV. The team investigated the three vibrational electron frequency modes of the spike protein using Raman spectroscopy for SARS-CoV-2 and plotted the results for three different frequencies: the different frequency vibrational modes showed similar effects.

From left to right: coupling at oscillator mode frequencies ω = 0.2069 eV, 0.1537 eV, and 0.1240 eV. The blue area shows transfer enhancement, the white area shows no enhancement, and the red area shows transfer reduction. Figures (a)-(d) all show the effect of an order of magnitude increase in dimer coupling strength from J=0.0001 eV to J=0.1 eV. These results effectively illustrate the (biologically relevant) parametric window for vibration-assisted tunneling effects.

03New opportunities for the development of drugs for new coronary infections and sequelae

1) New ideas for drug development

A better understanding of the various ways in which virus and host cells interact through molecular recognition and binding may lead to new therapies for COVID-19: the mechanism of receptor binding is an important factor in drug development. It has been suggested that treatment with ACE2 inhibitors may have implications for the severity of the disease; it has also been suggested that the introduction of soluble ACE2 may act on the virus by binding to the viral spike protein before the virus binds to the ACE2 receptor on the membrane; the ACE2 receptor also catalyzes the binding of different forms of angiotensin to the GPC receptor; ACE2 inhibitors may block the different angiotensin protein production, whereas angiotensin receptor blockers can block the action of angiotensin proteins.

Other GPCR agonists have been reported to be effective in alleviating COVID-19 infection. Histamine (Histamine) plays a role in neuromodulation and transmission in addition to mediating immune and allergic responses - it binds to some GPCRs; on the other hand, antihistamines bind to histamine GPCRs and act as blockers or inverse agonists: some antihistamines work by disrupting virus-host cell binding in a way that prevents SARS-CoV-2 infection. There remains some doubt as to whether nicotinic receptors function, at least in part, as GPCRs. However, these receptors do open ion channels. Although there is little debate as to whether smoking per se has any protective effect against COVID-19, nicotine may be a potential therapeutic intervention for severe disease. However, it remains unclear whether nicotine's effects are beneficial or harmful.

Extending the vibrational theory of olfaction to the binding of neurotransmitters, agonists and antagonists of certain ligands can also be classified according to their vibrational spectrum. In the context of SARS-CoV-2, screening and selection of relevant ligands by, for example, Raman spectroscopy may lead to the discovery of new therapeutic approaches. The different vibrational spectra of mutant spike proteins may also allow some prediction of the infectivity of new variants of SARS-CoV-2. ACE2 is a regulator of oxidative stress and it has been suggested that increased vulnerability to COVID-19 is associated with increased oxidative stress, through factors such as increased age or underlying health problems. Redox reactions are spiked in vivo, particularly in the electron transport chain within the mitochondria. Spike proteins have also been shown to directly regulate mitochondrial activity, most likely through ACE2 signaling. Regardless of whether spike proteins are involved, a growing number of studies suggest that mitochondria are associated with COVID-19 and therefore may inform new therapeutic options.

2) COVID-19 sequelae

While the involvement of redox, receptor binding mechanisms and GPCR in SARS-CoV-2 infection may lead to new therapeutic approaches for the disease, it may also provide insights into the post-viral condition known as "neocon sequelae". Research into this condition is still at a very early stage, and because of the large number of people who appear to experience long-term symptoms associated with COVID-19, more relevant research is urgently needed.

COVID-19 sequelae do not necessarily correlate with the severity of the active infection, with some patients reporting milder symptoms in the initial, acute phase of the disease before developing lasting sequelae. Some long-term effects may be due to damage caused by COVID-19 to organs such as the lungs and heart; however, of those who report long-term effects, a significant proportion have no obvious biomarkers to explain their bewildering collection of symptoms: from fatigue and joint pain to brain fog, memory problems, mood swings, and mental illness.

In the absence of a clear mechanism and a wide range of symptoms, the sequelae of COVID resemble myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS). Several studies have pointed to the involvement of the GPCR in ME and CFS, in particular the disruption of GPCR function by autoantibodies.GPC receptors control a wide range of essential functions and bind to a wide range of different ligands, which makes them excellent targets for drug development. However, this also means that specific ligands may interact with receptors other than their primary receptor, leading, for example, to side effects of GPCR-targeted drugs. it remains to be seen whether the COVID sequelae involve disruption of the GPCR. However, if ACE2 binds both to SARS-CoV-2 virus and to molecules such as angiotensin, then perhaps the virus could at least partially mimic the way angiotensin binds to GPCR, either through specific viral proteins or through autoantibodies.

GPCR disruption may also potentially explain the wide range of symptoms reported by patients with COVID, as GPCR is implicated in many different physiological processes. the involvement of GPCR in ion channels may also prove to be an avenue of research for potential therapeutic approaches. Viruses or groups of viruses play an important and not yet fully understood role in the human body. It is therefore conceivable that COVID sequelae are manifestations of some aspects of the SARS-CoV-2 virus being incorporated into host cells even beyond the infection stage. In particular, the envelope proteins of SARS-CoV-2 viruses have been shown to have the capacity to be virulins, and ion channels play an important role in maintaining a membrane potential that plays an important role in disease, particularly in cancer.

04Quantum biology: promising additional insights into new coronaviruses

This paper revolves around two related assertions: that quantum trypan effects are worth investigating in the various contexts in which molecular recognition and reception play a role; and that quantum trypan effects may be implicated in the receptor binding mode of the SARS-CoV-2 stinger protein, either through the action of enzymes or the involvement of GPCR.

These better understandings of receptor recognition may contribute to better medical interventions, and quantum biology may also provide a greater knowledge base for protection against SARS-CoV-2 viruses, as well as future novel viruses.

Reference：

https://www.nature.com/articles/s41598-022-21321-1