Existing bitter medicines for fighting COVID-19 associated infectious diseases
The sudden outbreak of COVID-19 has led to more than seven thousand deaths. Unfortunately, there are no specific drugs available to cure this disease. Type 2 taste receptors (TAS2Rs) may play an important role in host defense mechanisms. Based on the idea of host-directed therapy (HDT), we performed a negative co-expression analysis using big data of 60 000 Affymetrix expression arrays and 5000 TCGA data sets to determine the functions of TAS2R10, which can be activated by numerous bitter substances. Excitingly, we found that the main functions of TAS2R10 involved controlling infectious diseases caused by bacteria, viruses, and parasites, suggesting that TAS2R10 is a key trigger of host defense pathways. To quickly guide the clinical treatment of COVID-19, we searched currently available drugs that are agonists of TAS2Rs. We identified many cheap, available, and safe medicines, such as diphenidol, quinine, chloroquine, artemisinin, chlorpheniramine, yohimbine, and dextromethorphan, which may target the most common symptoms caused by COVID-19. We suggest that a cocktail-like recipe of existing bitter drugs may help doctors to fight this catastrophic disease and that the general public may drink or eat bitter substances, such as coffee, tea, or bitter vegetables, to reduce the risk of infection.
pubmed.ncbi.nlm.nih.gov
Chloroquine and COVID-19: role as a bitter taste receptor agonist?
COVID-19 is a world public health emergency caused by the new coronavirus, SARSCoV-2. Many drugs were repurposed as a treatment for COVID-19 patients including Chloroquine (CQ). CQ is a bitter taste receptor agonist reported to relax the airways suggesting a role in preventing disease severity of COVID-19 patients with asthma.
pubmed.ncbi.nlm.nih.gov
Bitter taste receptors as a therapeutic target for the clinical symptoms of COVID-19
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has paralysed the livelihood of the global population by inflicting higher mortality among the affected patients. Nearly the entire human physiological system can get disrupted by the virulence of SARS-CoV-2, which exemplifies the significance of discovering a potential drug target. Similar to angiotensin-converting enzyme 2 (ACE2), bitter taste receptors (T2Rs) unequivocally expressed on all vital human organs, particularly on nasal/oral respiratory tract, gastrointestinal organs, innate immune cells, heart, brain and urogenital cells are susceptible to SARS-CoV-2 virulence. Activation of T2Rs by bitter agonists restores vital functions to these organs via activation of large conductance, Ca2+-dependent potassium (K+) channels (BKca), and inducible nitric oxide synthase. T2R activation in the gustatory system can act as the first defence mechanism, primarily preventing or mitigating SARS-CoV-2 entry to the respiratory tract. Moreover, T2R activation is crucial for the improved vasodilation accompanied by the attenuation of systemic inflammation; hyper-innate immune responses; gastrointestinal disorders; defective neurological functions; acute kidney injury; and impotency witnessed in severe SARS-CoV-2 cases. This review discusses the potential for bitter taste receptors to act as drug targets for SARS-CoV-2 symptoms and the use of existing bitter agonists to restore T2R function.
pubmed.ncbi.nlm.nih.gov
Treatment Protocol for COVID-19 Based on T2R Phenotype
COVID-19 has become a global pandemic of the highest priority. Multiple treatment protocols have been proposed worldwide with no definitive answer for acure. A prior retrospective study showed association between bitter taste receptor 38 (T2R38) phenotypes and the severity of COVID-19. Based on this, we proposed assessing the different T2R38 phenotypes response towards a targeted treatment protocol. Starting July 2020 till December 2020, we tested subjects for T2R38 phenotypic expression (supertasters, tasters, and nontasters). Subjects who were subsequently infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (diagnosed via PCR) were included. Based on their taster status, supertasters were given dexamethasone for 4 days; tasters were given azithromycin and dexamethasone +/- hydroxychloroquine for 7 days; and nontasters were given azithromycin and dexamethasone for 12 days. Subjects were followed prospectively and their outcomes were documented. Seven hundred forty-seven COVID-19 patients were included, with 184 (24.7%) supertasters, 371 (49.6%) tasters, and192 (25.7%) nontasters. The average duration of symptoms with the treatment protocol was 5 days for supertasters, 8.1 days for tasters, and 16.2 days for nontasters. Only three subjects (0.4%) required hospitalization (3/3 nontasters). Targeted treatment protocol showed significant correlation (p < 0.05) based on patients' T2R38 phenotypic expression. Assessing treatment protocols for COVID-19 patients according to their T2R38 phenotype could provide insight into the inconsistent results obtained from the different studies worldwide. Further study is warranted on the categorization of patients based on their T2R38 phenotype.
pubmed.ncbi.nlm.nih.gov
BitterDB database, available at https://bitterdb.agri.huji.ac.il/dbbitter.php, includes over 1000 compounds that were reported to taste bitter to humans. The compounds can be searched by name, chemical structure, similarity to other bitter compounds, association with a particular human bitter taste receptor, and so on. The database also contains information on mutations in bitter taste receptors that were shown to influence receptor activation by bitter compounds.
A Number Of Bitter Compounds:
The sudden outbreak of COVID-19 has led to more than seven thousand deaths. Unfortunately, there are no specific drugs available to cure this disease. Type 2 taste receptors (TAS2Rs) may play an important role in host defense mechanisms. Based on the idea of host-directed therapy (HDT), we performed a negative co-expression analysis using big data of 60 000 Affymetrix expression arrays and 5000 TCGA data sets to determine the functions of TAS2R10, which can be activated by numerous bitter substances. Excitingly, we found that the main functions of TAS2R10 involved controlling infectious diseases caused by bacteria, viruses, and parasites, suggesting that TAS2R10 is a key trigger of host defense pathways. To quickly guide the clinical treatment of COVID-19, we searched currently available drugs that are agonists of TAS2Rs. We identified many cheap, available, and safe medicines, such as diphenidol, quinine, chloroquine, artemisinin, chlorpheniramine, yohimbine, and dextromethorphan, which may target the most common symptoms caused by COVID-19. We suggest that a cocktail-like recipe of existing bitter drugs may help doctors to fight this catastrophic disease and that the general public may drink or eat bitter substances, such as coffee, tea, or bitter vegetables, to reduce the risk of infection.
Bitter drug | Main clinical action | Responsive TAS2R member |
|---|---|---|
Diphenidol | Antiemetic (In, Wi) | 1,4,7,10,13,14,16,38,39,40,43,44,46,47,49 |
Quinine | Antimalarial; antipyretic; analgesic | 4,7,10,14,39,40,43,44,46 |
Chlorpheniramine | Anti‐allergy | 4,7,10,14,38,39,40,46 |
Denatonium benzoate | Anti‐feedant (No) | 4,8,10,13,39,43,46,47 |
Parthenolide | Anti‐allergic contact dermatitis (In) | 1,4,8,10,14,44,46 |
Arborescin | | 1,4,10,14,43,46 |
Chloramphenicol | Antibiotic (Ve) | 1,8,10,39,43,46 |
Cascarillin | | 1,10,14,46,47 |
Picrotoxinin | Experimental | 1,10,14,46,47 |
Quassin | | 4,10,14,46,47 |
Azathioprine | Immunosuppressive | 4,10,14,39,46 |
Artemorin | | 4,10,14,46,47 |
Papaverine | Antispasmodic (In) | 7,10,14,31,46 |
Caffeine | Anit‐apnea for newborn | 7,10,14,43,46 |
Yohimbine | Anti‐impotence (In, Ve) | 1,4,10,38,46 |
Chloroquine | Antimalarial;anti‐autoimmune (In, Ve) | 3,7,10,39 |
Camphor | Antipruritic and anti‐infective | 4,10,14,47 |
Dapsone | Anti‐leprosy (In) | 4,10,40 |
Strychnine | | 7,10,46 |
Dextromethorphan | Antitussive | 1,10 |
Haloperidol | Antipsychotic | 10,14 |
Brucine | | 10,46 |
Coumarin | Experimental | 10,14 |
Cucurbitacin B | | 10,14 |
Thujon, (‐)‐a‐ | | 10,14 |
Benzoin | Experimental (proved) | 10,14 |
Famotidine | Gastric acid Inhibitor | 10,44 |
Cucurbitacin E | | 10 |
Cycloheximide | | 10 |
Erythromycin | Antibiotic | 10 |
Diphenylthiourea | | 1,14,38 |
Colchicine | Anti‐gout | 4,39,46 |
Sodium benzoate | Food preservative (In) | 14,16 |
Diphenhydramine | Antihistamine (In) | 14,40 |
Carisoprodol | Muscle relaxant | 14,46 |
Noscapine | Antitussive (In) | 14 |
Benzamide | | 14 |
Chlorhexidine | Antiseptic (Ve) | 14 |
Divinylsulfoxid | | 14 |
Flufenamic acid | Anti‐inflamatory | 14 |
4‐Hydroxyanisol | | 14 |
Hydrocortisone | Glucocorticoid (Ve) | 46 |
Orphenadrine | Antispasmodic | 46 |
Tatridin B | | 46 |
Artemisinin | Antimalarial (In) | 46 |
Existing bitter medicines for fighting 2019-nCoV-associated infectious diseases - PubMed
The sudden outbreak of COVID-19 has led to more than seven thousand deaths. Unfortunately, there are no specific drugs available to cure this disease. Type 2 taste receptors (TAS2Rs) may play an important role in host defense mechanisms. Based on the idea of host-directed therapy (HDT), we...
pubmed.ncbi.nlm.nih.gov
Chloroquine and COVID-19: role as a bitter taste receptor agonist?
COVID-19 is a world public health emergency caused by the new coronavirus, SARSCoV-2. Many drugs were repurposed as a treatment for COVID-19 patients including Chloroquine (CQ). CQ is a bitter taste receptor agonist reported to relax the airways suggesting a role in preventing disease severity of COVID-19 patients with asthma.
Chloroquine and COVID-19: role as a bitter taste receptor agonist? - PubMed
COVID-19 is a world public health emergency caused by the new coronavirus, SARSCoV-2. Many drugs were repurposed as a treatment for COVID-19 patients including Chloroquine (CQ). CQ is a bitter taste receptor agonist reported to relax the airways suggesting a role in preventing disease severity...
pubmed.ncbi.nlm.nih.gov
Bitter taste receptors as a therapeutic target for the clinical symptoms of COVID-19
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has paralysed the livelihood of the global population by inflicting higher mortality among the affected patients. Nearly the entire human physiological system can get disrupted by the virulence of SARS-CoV-2, which exemplifies the significance of discovering a potential drug target. Similar to angiotensin-converting enzyme 2 (ACE2), bitter taste receptors (T2Rs) unequivocally expressed on all vital human organs, particularly on nasal/oral respiratory tract, gastrointestinal organs, innate immune cells, heart, brain and urogenital cells are susceptible to SARS-CoV-2 virulence. Activation of T2Rs by bitter agonists restores vital functions to these organs via activation of large conductance, Ca2+-dependent potassium (K+) channels (BKca), and inducible nitric oxide synthase. T2R activation in the gustatory system can act as the first defence mechanism, primarily preventing or mitigating SARS-CoV-2 entry to the respiratory tract. Moreover, T2R activation is crucial for the improved vasodilation accompanied by the attenuation of systemic inflammation; hyper-innate immune responses; gastrointestinal disorders; defective neurological functions; acute kidney injury; and impotency witnessed in severe SARS-CoV-2 cases. This review discusses the potential for bitter taste receptors to act as drug targets for SARS-CoV-2 symptoms and the use of existing bitter agonists to restore T2R function.
A hypothesis: Bitter taste receptors as a therapeutic target for the clinical symptoms of SARS-CoV-2 - PubMed
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has paralysed the livelihood of the global population by inflicting higher mortality among the affected patients. Nearly the entire human physiological system can get disrupted by the virulence of SARS-CoV-2, which...
pubmed.ncbi.nlm.nih.gov
Treatment Protocol for COVID-19 Based on T2R Phenotype
COVID-19 has become a global pandemic of the highest priority. Multiple treatment protocols have been proposed worldwide with no definitive answer for acure. A prior retrospective study showed association between bitter taste receptor 38 (T2R38) phenotypes and the severity of COVID-19. Based on this, we proposed assessing the different T2R38 phenotypes response towards a targeted treatment protocol. Starting July 2020 till December 2020, we tested subjects for T2R38 phenotypic expression (supertasters, tasters, and nontasters). Subjects who were subsequently infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (diagnosed via PCR) were included. Based on their taster status, supertasters were given dexamethasone for 4 days; tasters were given azithromycin and dexamethasone +/- hydroxychloroquine for 7 days; and nontasters were given azithromycin and dexamethasone for 12 days. Subjects were followed prospectively and their outcomes were documented. Seven hundred forty-seven COVID-19 patients were included, with 184 (24.7%) supertasters, 371 (49.6%) tasters, and192 (25.7%) nontasters. The average duration of symptoms with the treatment protocol was 5 days for supertasters, 8.1 days for tasters, and 16.2 days for nontasters. Only three subjects (0.4%) required hospitalization (3/3 nontasters). Targeted treatment protocol showed significant correlation (p < 0.05) based on patients' T2R38 phenotypic expression. Assessing treatment protocols for COVID-19 patients according to their T2R38 phenotype could provide insight into the inconsistent results obtained from the different studies worldwide. Further study is warranted on the categorization of patients based on their T2R38 phenotype.
Treatment Protocol for COVID-19 Based on T2R Phenotype - PubMed
COVID-19 has become a global pandemic of the highest priority. Multiple treatment protocols have been proposed worldwide with no definitive answer for acure. A prior retrospective study showed association between bitter taste receptor 38 (T2R38) phenotypes and the severity of COVID-19. Based on...
pubmed.ncbi.nlm.nih.gov
BitterDB database, available at https://bitterdb.agri.huji.ac.il/dbbitter.php, includes over 1000 compounds that were reported to taste bitter to humans. The compounds can be searched by name, chemical structure, similarity to other bitter compounds, association with a particular human bitter taste receptor, and so on. The database also contains information on mutations in bitter taste receptors that were shown to influence receptor activation by bitter compounds.
A Number Of Bitter Compounds:
