Siewiński M, Bażanów B, Orzechowska B
… +8 more, Gołąb K, Gburek J, Matkowski A, Rapak A, Janocha A, Krata L, Dobrzyński M, Kilar E
Med Hypotheses
· 2022 Nov · PMID 36313266
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Specific antibodies that humans acquire as a result of disease or after vaccination are needed to effectively suppress infection with a specific variant of SARS CoV-2 virus. The S protein of the D614G variant of coronavi...Specific antibodies that humans acquire as a result of disease or after vaccination are needed to effectively suppress infection with a specific variant of SARS CoV-2 virus. The S protein of the D614G variant of coronavirus is used as an antigen in known vaccines to date. It is known that COVID-19 disease resulting from infection with this coronavirus can often be very dangerous to the health and lives of patients. In contrast, vaccines produce antibodies against an older version of the protein S-D614G (January 2020) and therefore have difficulty recognizing new variants of the virus. In our project we propose to obtain specific and precise antibodies by means of so-called controlled infection against specific infectious variants of the SARS-CoV-2 virus "here and now". Currently, several variants of this pathogen have already emerged that threaten the health and lives of patients. We propose to reduce this threat by partially, but not completely, blocking the fusion mechanism of the SARS-CoV-2 virus into human respiratory cells. According to our plan, this can be achieved by inhibiting cathepsin L activity in respiratory cells, after introducing natural and non-toxic cysteine protease inhibitors into this area. We obtain these inhibitors by our own method from natural, "human body friendly" natural resources. We hypothesize that blocking cathepsin L will reduce the number of infecting viruses in cells to such an extent that COVID-19 developing in infected individuals will not threaten their health and life. At the same time, the number of viruses will be sufficient for the body's own immune system to produce precise antibodies against a specific version of this pathogen.
Med Hypotheses
· 2022 Oct · PMID 36157252
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Finding effective drugs to treat SARS-CoV-2 infection as a complementary step to the extensive vaccination is of the great importance to overcome the current pandemic situation. It has been shown that some bio-active uns...Finding effective drugs to treat SARS-CoV-2 infection as a complementary step to the extensive vaccination is of the great importance to overcome the current pandemic situation. It has been shown that some bio-active unsaturated fatty acids such as Arachidonic Acid (AA) can reduce the infection severity and even destroy the virus by disintegration of the virus lipid envelope. On the other hand, it has been reported that several designed peptides with an activity similar to the angiotensin converting enzyme 2 (ACE-2), which has a high affinity towards the novel corona virus spike protein, can inhibit the viral infection through concealing the spike proteins from the cell surfaces ACE-2. Binding the mentioned peptides to the bio-active lipids like AA will result in a lipopeptide surfactant molecule with the synergistic effect of both the active moieties in its structure to treat the novel corona infection. In addition, the peptide segment increases the aqueous solubility of the lipid segment and enables the targeted delivery of the surfactant molecule to the virus. The resultant lipopeptide would be a potentially effective drug for SARS-CoV-2 infection treatment with the minimum side effects.
Costa Silva RCM, Bandeira-Melo C, Paula Neto HA
… +2 more, Vale AM, Travassos LH
Med Hypotheses
· 2022 Oct · PMID 36105250
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SARS-CoV-2 infection intrigued medicine with diverse outcomes ranging from asymptomatic to severe acute respiratory syndrome (SARS) and death. After more than two years of pandemic, reports of reinfection concern researc...SARS-CoV-2 infection intrigued medicine with diverse outcomes ranging from asymptomatic to severe acute respiratory syndrome (SARS) and death. After more than two years of pandemic, reports of reinfection concern researchers and physicists. Here, we will discuss potential mechanisms that can explain reinfections, including the aggravated ones. The major topics of this hypothesis paper are the disbalance between interferon and antibodies responses, HLA heterogeneity among the affected population, and increased proportion of cytotoxic CD4+ T cells polarization in relation to T follicular cells (Tfh) subtypes. These features affect antibody levels and hamper the humoral immunity necessary to prevent or minimize the viral burden in the case of reinfections.
Med Hypotheses
· 2022 Apr · PMID 36060122
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To date, much of the focus of gut-brain axis research has been on gut microbiota regulation of anxiety and stress-related behaviors. Much less attention has been directed to potential connections between gut microbiota a...To date, much of the focus of gut-brain axis research has been on gut microbiota regulation of anxiety and stress-related behaviors. Much less attention has been directed to potential connections between gut microbiota and compulsive behavior. Here, we discuss a potential link between gut barrier dysfunction and compulsive behavior that is mediated through "type 2" rather than "type 1" inflammation. We examine connections between compulsive behavior and type 2 inflammation in Tourette syndrome, obsessive-compulsive disorder, autism, addiction, and post-traumatic stress disorder. Next, we discuss potential connections between gut barrier dysfunction, type 2 inflammation, and compulsive behavior. We posit a potential mechanism whereby gut barrier dysfunction-associated type 2 inflammation may drive compulsive behavior through histamine regulation of dopamine neurotransmission. Finally, we discuss the possibility of exploiting the greater accessibility of the gut relative to the brain in identifying targets to treat compulsive behavior disorders.
Das D, Bihari Jena A, Banerjee A
… +3 more, Kumar Radhakrishnan A, Duttaroy AK, Pathak S
Med Hypotheses
· 2022 Sep · PMID 35935095
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People living with HIV are more exposed to the adverse health effects of the worldwide COVID-19 pandemic. The pandemic's health and social repercussions may promote drug abuse and inadequate HIV management among this dem...People living with HIV are more exposed to the adverse health effects of the worldwide COVID-19 pandemic. The pandemic's health and social repercussions may promote drug abuse and inadequate HIV management among this demographic. The coronavirus pandemic of 2019 (COVID-19) has caused unprecedented disruption worldwide in people's lives and health care. When the COVID-19 epidemic was identified, people with HIV faced significant obstacles and hurdles to achieving optimal care results. The viral spike protein (S-Protein) and the cognate host cell receptor angiotensin-converting enzyme 2 (ACE2) are both realistic and appropriate intervention targets. Calanolides A, Holy Basil, Kuwanon-L, and Patentiflorin have anti-HIV effects. Our computational biology study investigated that these compounds all had interaction binding scores related to S protein of coronavirus of -9.0 kcal /mol, -7.1 kcal /mol, -9.1 kcal /mol, and -10.3 kcal/mol/mol, respectively. A combination of plant-derived anti-HIV compounds like protease inhibitors and nucleoside analogs, which are commonly used to treat HIV infection, might be explored in clinical trials for the treatment of COVID-19.
Targoński R, Gąsecka A, Prowancki A
… +1 more, Targoński R
Med Hypotheses
· 2022 Sep · PMID 35791352
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The Chinese scenario, a rapid increase in the frequency of SARS-CoV-2 infections and sudden decline, is uncommon worldwide. Enormous differences in COVID-19 severity among individual countries are the striking findings o...The Chinese scenario, a rapid increase in the frequency of SARS-CoV-2 infections and sudden decline, is uncommon worldwide. Enormous differences in COVID-19 severity among individual countries are the striking findings of the pandemics. It has been demonstrated that a mild course of COVID-19 is associated with gastrointestinal symptoms, less inflammatory response, and better prognosis. The presence of SARS-CoV-2 was observed longer in the gastrointestinal tract than in respiratory swabs, promoting feco-oral transmissions and mild virus attenuation. The spread of the pandemic and its severity might, consequently, depends on the dominant environmental route of infection and emerging immunity. We hypothesize that the feco-oral SARS-CoV-2 transmission may help to achieve the long-term immunity against COVID-19, since it enables the continuous contact with viral antigens in the gastrointestinal tract, resulting in lower mortality rate. To conclude, countries producing rice through traditional methods developed rapidly emerging long-lasting population immunity, possibly through increased SARS-CoV-2 antigen exposure in the gastrointestinal tract. Our hypothesis brings attention to this potential route of herd immunity against SARS-CoV-2 which warrants further investigation in the future.
Med Hypotheses
· 2022 Aug · PMID 35721254
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Since the inception of the pandemic, almost all countries have been testing Covid-19 via a swab test with one bar (combined OP and NP). They use the same bar - first an oropharynx swab and then a nasopharynx swab- This m...Since the inception of the pandemic, almost all countries have been testing Covid-19 via a swab test with one bar (combined OP and NP). They use the same bar - first an oropharynx swab and then a nasopharynx swab- This manner of application causes oropharengeal Covid-19 viruses to be inoculated into the nasopharynx and help grow Covid-19 disease infection in that area as well. We speculate that asymptomatic Covid- 19 carriers can be converted to pre-symptomatic people via auto-transmission iatrogenically. This highlights the critical role of asymptomatic cases in the progression of the ongoing pandemic. Also,infectivity can also be carried through nostrils to nasopharengeal area via manual intervention with one bar.
Med Hypotheses
· 2022 Jun · PMID 35698641
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Vaccinees experience no adverse events, mild adverse events, multiple adverse events, or serious adverse events post vaccination. Many of these vaccine adverse events occur with different vaccines with different occurren...Vaccinees experience no adverse events, mild adverse events, multiple adverse events, or serious adverse events post vaccination. Many of these vaccine adverse events occur with different vaccines with different occurrence frequencies. Many of these adverse events are generally considered as associated with immune responses to the active vaccine components (antigens) and/or to possibly one or more of the vaccine excipients. Most of these vaccine adverse events are self-limiting and resolve within days. Many of these adverse events symptoms overlap symptoms associated with elevated histamine levels. Based on these observations, the hypothesis that the majority of vaccine associated reactogenicity adverse events are caused by temporal histamine intolerance in vaccinees is proposed. This hypothesis is based on a model of innate immune responses releasing a surge of inflammatory molecules including histamine; this surge is hypothesized to exceed the normal histamine tolerance level for vaccinees with reactogenicity adverse events. Further, these symptoms resolve as histamine levels fall below the vaccinee's tolerance threshold. This model can be evaluated by the detection of elevated histamine levels in vaccinees corresponding to timing of symptoms onset. If confirmed, a direct consequence of this model predicts that some antihistamine treatments, mast cell stabilizers, and possibly diamine oxidase enzyme may reduce the incidence or severity of adverse events experienced by vaccinees post vaccinations for most or all high reactogenicity vaccines including coronavirus disease 2019 (COVID-19) Spike vaccines.
Med Hypotheses
· 2022 Jul · PMID 35620530
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Fungal co-infections of coronavirus disease 2019 (COVID-19) are generally infrequent, but are more common among patients with hematological diseases or severe cases in the intensive care unit (ICU). As fungal infections...Fungal co-infections of coronavirus disease 2019 (COVID-19) are generally infrequent, but are more common among patients with hematological diseases or severe cases in the intensive care unit (ICU). As fungal infections often carry a high mortality rate, preventing their development is considered important for patients with COVID-19. Caspofungin covers spp. and spp. as causative pathogens of fungal infections associated with COVID-19, and is known to have few side effects among antifungal drugs. Recent studies have shown that caspofungin is expected to inhibit the growth of severe acute respiratory syndrome coronavirus 2. In addition, the inhibitory effects of caspofungin on spleen tyrosine kinase-related intracellular signaling are anticipated to suppress the overproduction of proinflammatory cytokines and immune thrombosis, which are problems in severe COVID-19. Early use of caspofungin in patients with COVID-19 with hematological diseases or in the ICU may help prevent fungal infections and reduce severe cases in COVID-19 patients.
Dorgaleleh S, Naghipoor K, Hozhabrpour A
… +1 more, Vahidnezhad H
Med Hypotheses
· 2022 Jun · PMID 35464998
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Dyskeratosis Congenita (DC) is a rare and heterogeneous disease. This disorder is resulted from a defect in the telomere maintenance in stem cells. Telomerase RNA component, shelterin complex, and telomerase reverse tran...Dyskeratosis Congenita (DC) is a rare and heterogeneous disease. This disorder is resulted from a defect in the telomere maintenance in stem cells. Telomerase RNA component, shelterin complex, and telomerase reverse transcriptase are mutated in this disease. Many studies have previously confirmed shorter leukocyte telomere length in DC. On the other hand, the association between telomere length and Coronavirus disease 2019 (COVID-19) indicated that people with a short telomere background mostly show more severe symptoms related to COVID-19, and the mortality rate among them increases as well. Because patients with DC have an abnormally short telomere length, in the current study, we hypothesized that they are at higher risk of developing symptomatic COVID-19 that requires further clinical care.
Med Hypotheses
· 2022 Jun · PMID 35464997
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Recent studies have reported an impaired exercise response at cardiopulmonary exercise testing (CPET) during convalescence from coronavirus disease 2019 (COVID-19). In detail, these previous reports suggest the presence...Recent studies have reported an impaired exercise response at cardiopulmonary exercise testing (CPET) during convalescence from coronavirus disease 2019 (COVID-19). In detail, these previous reports suggest the presence of functional limitations in a consistent proportion of COVID-19 survivors, in the absence of relevant alterations of ventilatory and gas exchange parameters at CPET. Therefore, deconditioning has been proposed as the main mechanism of the reduced peak oxygen uptake in this clinical setting. This interpretation of the results is supported by the evidence that deconditioning is a recognized aspect of the post-intensive care syndrome, with acute sarcopenia being frequently observed among COVID-19 survivors. Here, we hypothesized the role of endothelial dysfunction as a key pathogenic mechanism of the functional limitations of COVID-19, including multisystem deconditioning and subsequent exercise intolerance.
Med Hypotheses
· 2022 Jun · PMID 35431403
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The treatment of post-acute sequelae of Covid-19 (PASC) has been informed primarily by symptomatic parallels with other chronic inflammatory syndromes. This manuscript takes a more systemic approach by examining how a ma...The treatment of post-acute sequelae of Covid-19 (PASC) has been informed primarily by symptomatic parallels with other chronic inflammatory syndromes. This manuscript takes a more systemic approach by examining how a marginal deficiency of tetrahydrobiopterin (BH4) resulting from mutations of the GCH1 (GTP cyclohydrolase 1) gene may result in the uncoupling of inducible Nitric Oxide Synthase (iNOS) early in the initial response of the innate immune system to SARS-CoV-2. The resulting production of superoxide instead of nitric oxide leads to a self-perpetuating cycle of oxidative stress with the potential to impair numerous metabolic processes and damage multiple organ systems. This marginal deficiency of BH4 may be exhibited by 30% or more of the patient population that have heterozygous or homozygous mutations of GCH1. As the cycle of oxidative stress continues, there is less BH4 available for other metabolic needs such as 1) resisting increased ferroptosis with its damage to organs, and 2) regulating the deactivation of the hyperinflammatory state. Finally, possible steps are proposed for clinical treatment of the hypothesized oxidative stress involved with PASC.
Ouerdane Y, Khlidj Y, Attia MS
… +1 more, Korissi R
Med Hypotheses
· 2022 May · PMID 35228771
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COVID-19 infection was mainly associated with respiratory symptoms, but lately, ischemic stroke (IS) has been reported in several cases. The incidence of IS in SARS-CoV-2 infection is increasing, and its mechanism is sti...COVID-19 infection was mainly associated with respiratory symptoms, but lately, ischemic stroke (IS) has been reported in several cases. The incidence of IS in SARS-CoV-2 infection is increasing, and its mechanism is still not fully understood. Calcitonin gene-related peptide (CGRP) -the abundantly expressed protein in the peripheral and central nervous system- showed low expression in SARS-CoV-2 patients. This peptide is strongly implicated in regulating cerebral blood flow (CBF) and improving neurological deficits after cerebral arterial occlusion. We assume that a possible interplay between the low circulating levels of CGRP may affect CBF, thus worsening the symptoms of IS in SARS-CoV-2 patients.
González-Menacho J, Villas-Roca M, Castañé H
… +3 more, Joven J, Camps J, Iftimie S
Med Hypotheses
· 2022 Apr · PMID 35221450
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Chronic headache is a frequent disorder that can cause a significant deterioration in the quality of life of the affected person. The COVID-19 pandemic is compelling all countries to develop a complete vaccination protoc...Chronic headache is a frequent disorder that can cause a significant deterioration in the quality of life of the affected person. The COVID-19 pandemic is compelling all countries to develop a complete vaccination protocol for the entire population. In this article, we present 8 clinical cases of patients suffering chronic headache which resolved completely or partially after vaccination. Five patients had migraine, 2 had a post-viral headache typical of COVID-19, and one had a headache induced by sexual activity. Resolution was complete in 3 cases, almost complete in 2 others, and a great improvement was observed in the other 3. We hypothesize that the administration of vaccines for COVID-19 can produce an improvement or the disappearance of symptoms in our patients by inhibiting synthesis of pro-inflammatory cytokines.
Med Hypotheses
· 2022 Apr · PMID 35221449
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The far-reaching effects of the SARS-CoV-2 pandemic have crippled the progress of the world today. With the introduction of newer and newer mutated variants of the virus, it has become necessary to have a vaccine that re...The far-reaching effects of the SARS-CoV-2 pandemic have crippled the progress of the world today. With the introduction of newer and newer mutated variants of the virus, it has become necessary to have a vaccine that remains useful against all the mutated strains of SARS-CoV-2. In this regard, peptide vaccines turn out to be a cheap alternative to the traditionally designed vaccines owing to their much quicker and computationally easier, and more robust design procedures. Here, in this article, we hypothesize that there are three possible peptide vaccine regions that can be targeted to prevent the surge of SARS-CoV-2. The candidates that were selected, were surface-exposed and were not sequestered by any neighbouring amino acids. They were also found to be capable of generating both B-cell and T-cell immune responses. Most importantly, none of them contains any spike protein mutation of the currently prevailing variants of SARS-CoV-2. From these findings, we have therefore concluded that these three regions can be used in wet labs for peptide vaccine design against the upcoming strains of SARS-CoV-2.
Med Hypotheses
· 2022 Apr · PMID 35185264
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Coronaviruses have received worldwide attention following several severe acute respiratory syndrome (SARS) epidemics. In 2019, the first case of coronavirus disease (COVID-19) caused by a novel coronavirus (SARS-coronavi...Coronaviruses have received worldwide attention following several severe acute respiratory syndrome (SARS) epidemics. In 2019, the first case of coronavirus disease (COVID-19) caused by a novel coronavirus (SARS-coronavirus 2 [CoV-2]) was reported. SARS-CoV-2 employs RNA-dependent RNA polymerase (RdRp) for genome replication and gene transcription. Recent studies have identified a sulfur (S) metal-binding site in the zinc center structures of the RdRp complex. This metal-binding site is essential for the proper functioning of the viral helicase. We hypothesize that the use of essential nutrients can permeabilize the cell membranes. The oxidation of the metal-binding site occurs via analogs of the essential S-containing amino acid, l-Methionine. l-Methionine can operate as a carrier, and its binding would cause the potential disassembly of RdRp via the S complex and drive methyl donors via a possible countercurrent exchange mechanism and electrical-chemical gradient leading to SARS-CoV-2 replication failure. Our previously published hypothesis on the control of cancer cell proliferation suggests that the presence of a novel disulfide/methyl- adenosine triphosphate pump as an energy source would allow this process. The S binding site in l-Methionine serves as a potential target cofactor for SARS-CoV RdRp, thus providing a possible avenue for the future development of vaccines and antiviral therapeutic strategies to combat COVID-19.
Med Hypotheses
· 2022 Mar · PMID 35185263
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Despite great public health advances achieved by COVID-19 vaccines, rare side effects may impact the public acceptance. Guillain-Barre Syndrome has increasingly been reported with adenoviral-based vaccines. This perspect...Despite great public health advances achieved by COVID-19 vaccines, rare side effects may impact the public acceptance. Guillain-Barre Syndrome has increasingly been reported with adenoviral-based vaccines. This perspective proposes a possible mechanism underlying this rare but clinically significant side effect thereby providing insights for improving our current vaccines against COVID-19.
Med Hypotheses
· 2022 Mar · PMID 35103033
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As well as causing respiratory lesions, the multi-organ complications caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are also well known. Combined with the epidemiological characteristics of SARS-...As well as causing respiratory lesions, the multi-organ complications caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are also well known. Combined with the epidemiological characteristics of SARS-CoV-2 with high transmission rate and low lethality, the impact of complications caused by its infection on infected individuals seems to be of greater concern. There has been evidence that viral infection is complicated by female reproductive impairment, but the mechanism by which SARS-CoV-2 impairs female fertility is unclear. In addition, RNA-GPS technology has revealed that the SARS-CoV-2 genome resides in mitochondria of the host cells and affects mitochondrial function. Considering the close relationship between mitochondria and female fertility, this paper takes mitochondrial hijacking as an entry point to elucidate the possible mechanisms by which SARS-CoV-2 affects female fertility through the mitochondrial hijacking pathway, which will be important for timely preventive measures and identification of therapeutic targets for infected women with reproductive needs, especially those with asymptomatic infection.