{"id":2685,"date":"2024-09-10T12:51:21","date_gmt":"2024-09-10T16:51:21","guid":{"rendered":"http:\/\/haidut.me\/?p=2685"},"modified":"2024-09-10T12:51:21","modified_gmt":"2024-09-10T16:51:21","slug":"pregnenolone-p5-may-treat-for-covid-19-by-increasing-dopamine","status":"publish","type":"post","link":"https:\/\/haidut.me\/?p=2685","title":{"rendered":"Pregnenolone (P5) may treat for COVID-19, by increasing dopamine"},"content":{"rendered":"<p>A very interesting study, which is bound to be labelled as &#8220;controversial&#8221; and my post about it will probably get censored on Twitter\/X and other social media if\/when it gets shared there. Given that the mechanism of action reported by the study (dopamine enhancement) is so generic, the findings of the study possibly apply to other respiratory viral infections (URTI) too, which should not only make P5 a candidate for treating influenza, cold, and the rest of the viruses responsible for URTI, but may obviate the need for vaccines against those viruses if P5 intake is regular (as it is for most people who use it). Years ago, I posted about studies showing that cholesterol and progesterone also have protective effects in severe influenza infections, which suggests that one of the reasons for ever-increasing magnitude and severity of viral pandemics may be due to the widespread use of statins, as well as hormonal birth control in women. The reason I mention birth control is that despite most hormonal contraceptives containing synthetic progestins , most of those progestins have been found to behave nothing like bioidentical progesterone (which is very rarely used clinically) and (many\/most) are in fact potent agonists of the estrogen receptor(s).<\/p>\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39201608\">https:\/\/pubmed.ncbi.nlm.nih.gov\/39201608<\/a><\/p>\n<p>&#8220;&#8230;n the post-COVID-19 era, treatment options for potential SARS-CoV-2 outbreaks remain limited. An increased incidence of central nervous system (CNS) disorders has been observed in long-term COVID-19 patients. Understanding the shared molecular mechanisms between these conditions may provide new insights for developing effective therapies. This study developed an integrative drug-repurposing framework for COVID-19, leveraging comorbidity data with CNS disorders, network-based modular analysis, and dynamic perturbation analysis to identify potential drug targets and candidates against SARS-CoV-2. We constructed a comorbidity network based on the literature and data collection, including COVID-19-related proteins and genes associated with Alzheimer\u2019s disease, Parkinson\u2019s disease, multiple sclerosis, and autism spectrum disorder. Functional module detection and annotation identified a module primarily involved in protein synthesis as a key target module, utilizing connectivity map drug perturbation data. Through the construction of a weighted drug\u2013target network and dynamic network-based drug-repurposing analysis, ubiquitin\u2013carboxy-terminal hydrolase L1 emerged as a potential drug target. Molecular dynamics simulations <span style=\"text-decoration: underline;\"><strong>suggested <span style=\"color: #ff0000; text-decoration: underline;\">pregnenolone<\/span><\/strong><\/span> and BRD-K87426499 <span style=\"text-decoration: underline;\"><strong>as<\/strong><\/span> two <span style=\"text-decoration: underline;\"><strong>drug candidates for COVID-19<\/strong><\/span>. This study introduces a dynamic-perturbation-network-based drug-repurposing approach to identify COVID-19 drug targets and candidates by incorporating the comorbidity conditions of CNS disorders.&#8221;<\/p>\n<p>&#8220;&#8230;Many <span style=\"text-decoration: underline;\"><strong>candidate drugs have been proposed as repurposable drugs against SARS-CoV-2<\/strong><\/span> infection, such as a group of kinase inhibitors [<a class=\" bibr popnode\" role=\"button\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11354300\/#B26-ijms-25-08917\" aria-expanded=\"false\" aria-haspopup=\"true\">26<\/a>,<a class=\" bibr popnode\" role=\"button\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11354300\/#B52-ijms-25-08917\" aria-expanded=\"false\" aria-haspopup=\"true\">52<\/a>], estrogen receptor modulators [<a class=\" bibr popnode\" role=\"button\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11354300\/#B53-ijms-25-08917\" aria-expanded=\"false\" aria-haspopup=\"true\">53<\/a>], microtubule-regulating agents [<a class=\" bibr popnode\" role=\"button\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11354300\/#B54-ijms-25-08917\" aria-expanded=\"false\" aria-haspopup=\"true\">54<\/a>], HCV inhibitors [<a class=\" bibr popnode\" role=\"button\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11354300\/#B55-ijms-25-08917\" aria-expanded=\"false\" aria-haspopup=\"true\">55<\/a>], and <span style=\"text-decoration: underline;\"><strong>H1 antihistamines<\/strong><\/span> [<a class=\" bibr popnode\" role=\"button\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11354300\/#B27-ijms-25-08917\" aria-expanded=\"false\" aria-haspopup=\"true\">27<\/a>]. Notably, several drugs active in the CNS have been identified as repurposable for COVID-19, following SAveRUNNER analysis, such as <span style=\"text-decoration: underline;\"><strong>dopaminergics<\/strong> <\/span>and dopamine antagonists [<a class=\" bibr popnode\" role=\"button\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11354300\/#B56-ijms-25-08917\" aria-expanded=\"false\" aria-haspopup=\"true\">56<\/a>]. Herein, we proposed a series of <span style=\"text-decoration: underline;\"><strong>dopamine-related drugs as potential drugs for COVID-19 treatment, <span style=\"color: #ff0000; text-decoration: underline;\">especially pregnenolone<\/span><\/strong><\/span> and BRD-K87426499. <span style=\"text-decoration: underline;\"><strong><span style=\"color: #ff0000; text-decoration: underline;\">Pregnenolone, as a dopamine release enhancer<\/span>, is closely linked to the role of UCHL1 in regulating the dopamine system<\/strong><\/span>. UCHL1 may affect the function of dopaminergic neurons by participating in the processing of alpha-synuclein and reducing its accumulation, thereby inhibiting the production of alpha-synuclein aggregates in PD. Concurrently, <span style=\"text-decoration: underline;\"><strong>it promotes dopamine release in the SCNS, which can alleviate local and systemic damage to the dopamine system and slow the progression of AD<\/strong><\/span>. <span style=\"text-decoration: underline;\"><strong>This drug\u2019s MOA in AD and PD suggests that <span style=\"color: #ff0000; text-decoration: underline;\">pregnenolone<\/span><\/strong><\/span> and BRD-K87426499 <span style=\"text-decoration: underline; color: #ff0000;\"><strong>may have a similar therapeutic effect in treating COVID-19<\/strong><\/span>.&#8221;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>A very interesting study, which is bound to be labelled as &#8220;controversial&#8221; and my post about it&#8230;<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[2],"tags":[1886,1132,594,1401,922,6,1364,898],"class_list":["post-2685","post","type-post","status-publish","format-standard","hentry","category-science","tag-cold","tag-covid-19","tag-dopamine","tag-flu","tag-p5","tag-pregnenolone","tag-sars-cov-2","tag-virus","wpcat-2-id"],"_links":{"self":[{"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/posts\/2685","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/haidut.me\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=2685"}],"version-history":[{"count":1,"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/posts\/2685\/revisions"}],"predecessor-version":[{"id":2686,"href":"https:\/\/haidut.me\/index.php?rest_route=\/wp\/v2\/posts\/2685\/revisions\/2686"}],"wp:attachment":[{"href":"https:\/\/haidut.me\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2685"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/haidut.me\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2685"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/haidut.me\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2685"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}