Purification, Characterization, cDNA Cloning, and Bioinformatic Analysis of Zinc-Binding Protein from Magallana hongkongensis.

Oysters contain significant amounts of the zinc element, which may also be found in their proteins. In this study, a novel zinc-binding protein was purified from the mantle of the oyster Magallana hongkongensis using two kinds of gel filtration chromatograms. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that its molecular weight was approximately 36 kDa. The protein identified by the Q-Exactive mass spectrometer shared the highest sequence identity with carbonic anhydrase derived from Crassostrea gigas concerning amino acid sequence similarity. Based on homologous cloning and RACE PCR, the full-length cDNA of carbonic anhydrase from Magallana hongkongensis (designated as MhCA) was cloned and sequenced. The cDNA of MhCA encodes a 315-amino-acid protein with 89.74% homology to carbonic anhydrase derived from Crassostrea gigas. Molecular docking revealed that the two zinc ions primarily form coordination bonds with histidine residues in the MhCA protein. These results strongly suggest that MhCA is a novel zinc-binding protein in Magallana hongkongensis.

Novel sulfonamide-phosphonate conjugates as carbonic anhydrase isozymes inhibitors.

The three-components one-pot Kabachnik-Fields reaction of sulfapyridine, diethyl phosphite, and aldehyde under thermal catalysis reaction condition in the presence of bismuth (III) triflate as a catalyst afford the corresponding sulfonamide-phosphonates (3a-3p) in good to excellent yields (78%-91%). The structures of the new synthesized compounds were elucidated and confirmed by variable spectroscopic studies. Single crystal X-ray studies for 3a, 3d, and 3i verified the proposed structure. The newly developed sulfonamide-phosphonates were evaluated for their inhibitory properties against four isoforms of human carbonic anhydrase (hCA I, II, IX, and XII). The results demonstrated that they exhibited greater potency in inhibiting hCA XII compared to hCA I, II, and IX, with Ki ranging from 5.1 to 51.1 nM. Compounds 3l and 3p displayed the highest potency, exhibiting selectivity ratios of I/XII >298.7 and 8.5, and II/XII ratios of 678.1 and 142.1, respectively. Molecular docking studies were conducted to explore their binding patterns within the binding pocket of CA XII. The results revealed that the sulfonamide NH group coordinated with the Zn2+ ion, and hydrogen bond interactions were observed with residue Thr200. Additionally, hydrophobic interactions were identified between the benzenesulfonamide phenyl ring and Leu198. Compounds 3p and 3l exhibited an additional hydrogen bonding interaction with other amino acid residues. These supplementary interactions may contribute to the enhanced potency and selectivity of these compounds toward the CA XII isoform.

A carbonic anhydrase-targeted NIR-II fluorescent cisplatin theranostic nanoparticle for combined therapy of pancreatic tumors.

Optically active organic nanoparticles capable of emitting strong near-infrared II (NIR-II) fluorescence and eliciting tumor hyperthermia are promising for tumor imaging and photothermal therapy (PTT). However, their applications for the treatment of pancreatic tumors via mere PTT are challenging as both the nanoparticles and light are hard to enter the deeply located pancreatic tumors. Here, we report a NIR-II light excitable, carbonic anhydrase (CA)-targeting cisplatin prodrug-decorated nanoparticle (IRNPs-SBA/PtIV) for NIR-II fluorescence imaging (FLI)-guided combination PTT and chemotherapy of pancreatic tumors. IRNPs-SBA/PtIV is designed to hold a high photothermal conversion efficiency (PCE ≈ 65.17 %) under 1064 nm laser excitation, a strong affinity toward CA (Kd = 14.40 ± 5.49 nM), and a prominent cisplatin release profile in response to glutathione (GSH) and 1064 nm laser irradiation. We show that IRNPs-SBA/PtIV can be actively delivered into pancreatic tumors where the CA is upregulated, and emits NIR-II fluorescence to visualize tumors with a high sensitivity and penetration depth under 980 nm laser excitation. Moreover, the tumor-resided IRNPs-SBA/PtIV can efficiently inhibit the CA activity and consequently, relieve the acidic and hypoxic tumor microenvironment, benefiting to intensify chemotherapy. Guided by the NIR-II FLI, IRNPs-SBA/PtIV is capable of efficiently inhibiting pancreatic tumor growth via combinational PTT and chemotherapy with 1064 nm laser excitation under a low-power density (0.5 W cm-2, 10 min). This study demonstrates promise to fabricate NIR-II excitable nanoparticles for FLI-guided precise theranostics of pancreatic tumors.

Direct Biocatalytic Processes for CO2 Capture as a Green Tool to Produce Value-Added Chemicals.

Direct biocatalytic processes for CO2 capture and transformation in value-added chemicals may be considered a useful tool for reducing the concentration of this greenhouse gas in the atmosphere. Among the other enzymes, carbonic anhydrase (CA) and formate dehydrogenase (FDH) are two key biocatalysts suitable for this challenge, facilitating the uptake of carbon dioxide from the atmosphere in complementary ways. Carbonic anhydrases accelerate CO2 uptake by promoting its solubility in water in the form of hydrogen carbonate as the first step in converting the gas into a species widely used in carbon capture storage and its utilization processes (CCSU), particularly in carbonation and mineralization methods. On the other hand, formate dehydrogenases represent the biocatalytic machinery evolved by certain organisms to convert CO2 into enriched, reduced, and easily transportable hydrogen species, such as formic acid, via enzymatic cascade systems that obtain energy from chemical species, electrochemical sources, or light. Formic acid is the basis for fixing C1-carbon species to other, more reduced molecules. In this review, the state-of-the-art of both methods of CO2 uptake is assessed, highlighting the biotechnological approaches that have been developed using both enzymes.

Selenium-analogs based on natural sources as cancer-associated carbonic anhydrase isoforms IX and XII inhibitors.

In the relentless search for new cancer treatments, organoselenium compounds, and carbonic anhydrase (CA) inhibitors have emerged as promising drug candidates. CA isoforms IX and XII are overexpressed in many types of cancer, and their inhibition is associated with potent antitumor/antimetastatic effects. Selenium-containing compounds, particularly selenols, have been shown to inhibit tumour-associated CA isoforms in the nanomolar range since the properties of the selenium atom favour binding to the active site of the enzyme. In this work, two series of selenoesters (1a-19a and 1b-19b), which gathered NSAIDs, carbo/heterocycles, and fragments from natural products, were evaluated against hCA I, II, IX, and XII. Indomethacin (17b) and flufenamic acid (19b) analogs exhibited selectivity for tumour-associated isoform IX in the low micromolar range. In summary, selenoesters that combine NSAIDs with fragments derived from natural sources have been developed as promising nonclassical inhibitors of the tumour-associated CA isoforms.

Urease and Carbonic Anhydrase Inhibitory Effect of Xanthones from Aspergillus nidulans, an Endophytic Fungus of Nyctanthes arbor-tristis.

Urease plays a major role in the pathogenesis of peptic and gastric ulcer and also causes acute pyelonephritis and development of infection-induced reactive arthritis. Carbonic anhydrases (CA) cause pathological disorders such as epilepsy (CA I), glaucoma, gastritis, renal, pancreatic carcinomas, and malignant brain tumors (CA II). Although various synthetic urease and carbonic anhydrase inhibitors are known, these have many side effects. Hence, present studies were undertaken on ethyl acetate extract of Aspergillus nidulans, an endophytic fungus separated from the leaves of Nyctanthes arbor-tristis Linn. and led to the isolation of five furanoxanthones, sterigmatin (1: ), sterigmatocystin (3: ), dihydrosterigmatocystin (4: ), oxisterigmatocystin C (5: ), acyl-hemiacetal sterigmatocystin (6: ), and a pyranoxanthone (2: ). Acetylation of 3: gave compound O-acetyl sterigmatocystin (7: ). Their chemical structures were elucidated by 1H and 13C NMR and MS. The inhibitory effect of isolated compounds was evaluated on urease and carbonic anhydrase (bCA II) enzymes in vitro. Compounds 3: and 6: showed significant urease inhibition (IC50 19 and 21 µM), while other compounds exhibited varying degrees of urease inhibition (IC50 33 - 51 µM). Compounds 4, 6: and 7: exhibited significant inhibition of bCA II (IC50 values 21, 25 and 18 µM respectively), compounds 1: -3: displayed moderate inhibition (IC50 61, 76 and 31 µM respectively) while 5: showed no inhibition. A mechanistic study of the most active urease inhibitors was also performed using enzyme kinetics and molecular docking. All compounds were found non-toxic on the NIH-3T3 cell line.

Multifaced Assessment of Antioxidant Power, Phytochemical Metabolomics, In-Vitro Biological Potential and In-Silico Studies of Neurada procumbens L.: An Important Medicinal Plant.

This work was undertaken to explore the phytochemical composition, antioxidant, and enzyme-inhibiting properties of Neurada procumbens L. extracts/fractions of varying polarity (methanol extract and its fractions including n-hexane, chloroform, n-butanol, and aqueous fractions). A preliminary phytochemical study of all extracts/fractions, HPLC-PDA polyphenolic quantification, and GC-MS analysis of the n-hexane fraction were used to identify the phytochemical makeup. Antioxidant (DPPH), enzyme inhibition (against xanthine oxidase, carbonic anhydrase, and urease enzymes), and antibacterial activities against seven bacterial strains were performed for biological investigation. The GC-MS analysis revealed the tentative identification of 22 distinct phytochemicals in the n-hexane fraction, the majority of which belonged to the phenol, flavonoid, sesquiterpenoid, terpene, fatty acid, sterol, and triterpenoid classes of secondary metabolites. HPLC-PDA analysis quantified syringic acid, 3-OH benzoic acid, t-ferullic acid, naringin, and epicatechin in a significant amount. All of the studied extracts/fractions displayed significant antioxidant capability, with methanol extract exhibiting the highest radical-scavenging activity, as measured by an inhibitory percentage of 81.4 ± 0.7 and an IC50 value of 1.3 ± 0.3. For enzyme inhibition experiments, the n-hexane fraction was shown to be highly potent against xanthine oxidase and urease enzymes, with respective IC50 values of 2.3 ± 0.5 and 1.1 ± 0.4 mg/mL. Similarly, the methanol extract demonstrated the strongest activity against the carbonic anhydrase enzyme, with an IC50 value of 2.2 ± 0.4 mg/mL. Moreover, all the studied extracts/fractions presented moderate antibacterial potential against seven bacterial strains. Molecular docking of the five molecules ß-amyrin, campesterol, ergosta-4,6,22-trien-3ß-ol, stigmasterol, and caryophyllene revealed the interaction of these ligands with the investigated enzyme (xanthine oxidase). The results of the present study suggested that the N. procumbens plant may be evaluated as a possible source of bioactive compounds with multifunctional therapeutic applications.

Efficacy of Phytochemicals Derived from Roots of Rondeletia odorata as Antioxidant, Antiulcer, Diuretic, Skin Brightening and Hemolytic Agents-A Comprehensive Biochemical and In Silico Study.

Roots of Rondeletia odorata are a rich source of phytochemicals with high antioxidant potential and thus may possess health benefits. This study used the LC-MS technique to identify phytoconstituents in R. odorata roots extract/fractions. Results revealed that n-butanol fraction and ethanolic extract contained total phenolic and flavonoid contents with values of 155.64 ± 0.66 mgGAE/g DE and 194.94 ± 0.98 mgQE/g DE, respectively. Significant potential of antioxidants was observed by DPPH, CUPRAC and FRAP methods while the ABTS method showed moderate antioxidant potential. Maximum % inhibition for urease, tyrosinase and carbonic anhydrase was shown by ethanolic extract (73.39 ± 1.11%), n-butanol soluble fraction (80.26 ± 1.59%) and ethyl acetate soluble fraction (76.50 ± 0.67%) which were comparable with thiourea (standard) (98.07 ± 0.74%), kojic acid (standard) (98.59 ± 0.92%) and acetazolamide (standard) (95.51 ± 1.29%), respectively, while all other extract/fractions showed moderate inhibition activity against these three enzymes. Hemolytic activity was also observed to range from 18.80 ± 0.42 to 3.48 ± 0.69% using the standard (triton X-100) method. In total, 28 and 20 compounds were identified tentatively by LC-MS analysis of ethanolic extract and n-butanol soluble fraction, respectively. Furthermore, molecular docking was undertaken for major compounds identified by LC-MS for determining binding affinity between enzymes (urease, tyrosinase and carbonic anhydrase) and ligands. It was concluded that active phytochemicals were present in roots of R. odorata with potential for multiple pharmacological applications and as a latent source of pharmaceutically important compounds. This should be further explored to isolate important constituents that could be used in treating different diseases.

Assessment of phytotoxic, genotoxic and enzyme inhibition potential of.

OBJECTIVE: To evaluate Sterculia diversifolia stem bark and leaves for phytotoxic, genotoxic and enzymes inhibition potential. METHODS: Phytotoxic activity of both stem bark and leaves were screened using Lemna minor. The genotoxic activity of Sterculia diversifolia stem bark and leaves extracts were tested using comet assay protocol while enzyme inhibition activity of crude extract and various fractions of both stem bark and leaves were evaluated using acetyl cholinesterase, lipoxygenase, ß-glu-curonidase, urease, xanthine oxidase and carbonic anhydrase. RESULTS: Phytotoxic activity showed significant results in dose dependant manner in both stem bark (ethyl acetate and n-butanol) and leaves (ethyl acetate, n-butanol and n-hexane) fractions. In genotoxic activity, dichloromethane fraction showed significant activity followed by ethyl acetate fraction. Acetyl cholinesterease inhibitory activity showed significant results in both stem bark and leaves fractions, while significant lipoxygenase inhibition was shown by ethyl acetate, dichloromethane, crude extract and n-hexane fractions of both stem bark and leaves. ß-glucuronidase, urease and carbonic anhydrase inhibitory activity showed highly significant results in ethyl acetate fraction of both stem bark and leaves, while xanthine oxidase inhibition was shown by dichloromethane fraction of stem bark and leaves extracts. CONCLUSIONS: This study emphasizes the important phytotoxic, genotoxic and enzyme inhibition effects of Sterculia diversifolia stem bark and leaves. Hence, it is clear that Sterculia diversifolia stem bark and leaves possess phytotoxic, genotoxic and enzyme inhibitory agents.

In vitro differentiation of human pancreatic duct-derived PANC-1 cells into ß-cell phenotype using Tinospora cordifolia.

Type 1 diabetes mellitus is an autoimmune disorder leading to loss of beta cells. There is a dire need to inhibit apoptosis and induce regeneration of new beta cells. There are plants in the Indian medicine system having the potential for rejuvenation. In the present study, we have attempted to evaluate the capacity of aqueous extract of Tinospora cordifolia to regenerate beta cells from PANC-1 ductal cells. After differentiation, the characterization of ß-cell phenotype was carried out using dithizone and Gomori's staining and further confirmed by mRNA expression study of insulin, Pdx-1, and carbonic anhydrase-9. Insulin production was estimated with ELISA. Aqueous extract of Tinospora cordifolia at 15 µg/ml concentration can effectively induce differentiation of PANC-1 cells into beta cells. The morphological observations showed brownish-colored dithizone and purple-colored Gomori's staining. The ß-cells demonstrated significant mRNA expression of insulin and Pdx-1 and downregulation of carbonic anhydrase-9. The functionality of beta cells was demonstrated by 1.5-fold increase in insulin secretion in response to high glucose. Tinospora cordifolia has potential to differentiate PANC-1 ductal cells into functional beta cells and can be a lead towards non-invasive treatment of type 1 diabetes mellitus.

Dual-Energy CT Perfusion of Invasive Tumor Front in Non-Small Cell Lung Cancers.

Background Active endothelial cell proliferation occurs at the tumor edge, known as the invading-tumor front. This study focused on perfusion analysis of non-small cell lung cancers. Purpose To analyze dual-phase, dual-energy CT perfusion according to the degree of tumor hypoxia. Materials and Methods This prospective study was performed 2016-2017. A two-phase dual-energy CT protocol was obtained for consecutive participants with operable non-small cell lung cancer. The first pass and delayed iodine concentration within the tumor and normalized iodine uptake, corresponding to the iodine concentration within the tumor normalized to iodine concentration within the aorta, were calculated for the entire tumor and within three peripheral layers automatically segmented (ie, 2-mm-thick concentric subvolumes). The expression of the membranous carbonic anhydrase (mCA) IX, a marker of tumor hypoxia, was assessed in tumor specimens. Comparative analyses according to the histologic subtypes, type of resected tumors, and mCA IX expression were performed. Results There were 33 mCA IX-positive tumors and 16 mCA IX-negative tumors. In the entire tumor, the mean normalized iodine uptake was higher on delayed than on first-pass acquisitions (0.35 ± 0.17 vs 0.13 ± 0.15, respectively; P < .001). A single layer, located at the edge of the tumor, showed higher values of the iodine concentration (median, 0.53 mg/mL vs 0.21 mg/mL, respectively; P = .03) and normalized iodine uptake (0.04 vs 0.02, respectively; P = .03) at first pass in mCA IX-positive versus mCA IX-negative tumors. Within this layer, a functional profile of neovascularization was found in 23 of 33 (70%) of mCA IX-positive tumors, and the median mCA IX score of these tumors was higher than in tumors with a nonfunctional profile of neovascularization (median mCA IX score, 20 vs 2, respectively; P = .03). Conclusion A two-phase dual-energy CT examination depicted higher perfusion between the tumor edge and lung parenchyma in hypoxic tumors. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Murphy and Ryan in this issue.

Metal accumulation induces oxidative stress and alters carbonic anhydrase activity in corals and symbionts from the largest reef complex in the South Atlantic ocean.

We evaluated the influence of metal accumulation on the oxidative status [lipid peroxidation (LPO) and total antioxidant capacity (TAC)] and carbonic anhydrase (CA) activity in host and symbionts of the coral Mussismilia harttii and the hydrocoral Millepora alcicornis collected in Abrolhos Reef Banks (Northeast Brazil), potentially impacted by a major mine dam rupture. Considering metal levels measured in reefs worldwide, Abrolhos corals had higher Fe and Mn levels than expected for preserved offshore reefs. Increasing concentrations of arsenic (As), chromium (Cr) and manganese (Mn) drove inhibition of CA and increased oxidative damage in the hydrocoral M. alcicornis. The impairment of enzymatic activity in the symbiotic algae of M. alcicornis may be related to the oxidative stress condition. The hydrocoral M. alcicornis was more affected by metals than the coral M. harttii, which did not show the expected CA inhibition after metal exposure. Our results suggest that CA activity can be applied as a complementary biomarker to evaluate the physiological impacts of environmental metal contamination in reefs. Also, the metal levels and biochemical biomarkers reported in the present study may provide reference data to monitor the health of reefs impacted by a relevant dam rupture.

Repurposing FDA-approved sulphonamide carbonic anhydrase inhibitors for treatment of Neisseria gonorrhoeae.

Neisseria gonorrhoeae is a high-priority pathogen of concern due to the growing prevalence of resistance development against approved antibiotics. Herein, we report the anti-gonococcal activity of ethoxzolamide, the FDA-approved human carbonic anhydrase inhibitor. Ethoxzolamide displayed an MIC50, against a panel of N. gonorrhoeae isolates, of 0.125 µg/mL, 16-fold more potent than acetazolamide, although both molecules exhibited almost similar potency against the gonococcal carbonic anhydrase enzyme (NgCA) in vitro. Acetazolamide displayed an inhibition constant (Ki) versus NgCA of 74 nM, while Ethoxzolamide's Ki was estimated to 94 nM. Therefore, the increased anti-gonococcal potency of ethoxzolamide was attributed to its increased permeability in N. gonorrhoeae as compared to that of acetazolamide. Both drugs demonstrated bacteriostatic activity against N. gonorrhoeae, exhibited post-antibiotic effects up to 10 hours, and resistance was not observed against both. Taken together, these results indicate that acetazolamide and ethoxzolamide warrant further investigation for translation into effective anti-N. gonorrhoeae agents.

Matrine injection inhibits pancreatic cancer growth via modulating carbonic anhydrases- a network pharmacology-based study with in vitro validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Matrine injection is a complex mixture of plant bioactive substances extracted from Sophora flavescens Aiton and Smilax glabra Roxb. Since its approval by the Chinese Food and Drug Administration (CFDA) in 1995, Matrine injection has been clinically used as a complementary and alternative treatment for various cancers; however, the underlying mechanism of pancreatic cancer treatment is yet to be elucidated. AIM OF THE STUDY: The present study explores the potential mechanism of matrine injection on pancreatic cancer through network pharmacology technique and in vitro experimental validation. MATERIALS AND METHODS: Genes differentially expressed in pancreatic cancer were obtained from the Gene Expression Omnibus (GEO) database (GSE101448). The potential active components of matrine injection were selected following a literature search, and target prediction was performed by the SwissTarget Prediction database. Overlapping genes associated with survival were screened by the Gene Expression Profiling Interactive Analysis (GEPIA) database. In vitro experimental validation was performed with cell counting kit-8 (CCK-8) assay, apoptosis detection, cell cycle analysis, immunoblotting, and co-immunoprecipitation of the identified proteins. RESULTS: One thousand seven hundred genes differentially expressed among pancreatic tumor and non-tumor tissues were screened out. Sixteen active components and 226 predicted target genes were identified in matrine injection. A total of 25 potential target genes of matrine injection for the treatment of pancreatic cancer were obtained. Among them, the prognostic target genes carbonic anhydrase 9 (CA9) and carbonic anhydrase 12 (CA12) based on the GEPIA database are differently expressed in tumors compared to adjacent normal tissue. In vitro experiments, the results of CCK-8 assay, apoptosis and cell cycle analysis, immunoblotting, and co-immunoprecipitation showed that matrine injection inhibited Capan-1 and Mia paca-2 proliferation, arrested the cell cycle at the S phase, and induced apoptosis through up-regulated CA12 and down-regulated CA9. CONCLUSIONS: In this study, bioinformatics and network pharmacology were applied to explore the treatment mechanism on pancreatic cancer with matrine injection. This study demonstrated that matrine injection inhibited proliferation, arrested the cell cycle, and induced apoptosis of pancreatic cancer cells. The mechanism may be related to the induction of CA12 over-expression, and CA9 reduced expression. As novel targets for pancreatic cancer treatment, Carbonic anhydrases require further study.

Quantitative Characterization of the Chemical Space Governed by Human Carbonic Anhydrases and selenium-containing derivatives of solfonamides

Abstract Due to the fact that different isoforms of carbonic anhydrase play distinct physiological roles, their diseases/disorders involvement are different as well. Involvement in major disorders such as glaucoma, epilepsy, Alzheimer's disease, obesity and cancers, have turned carbonic anhydrase into a popular case study in the field of rational drug design. Since carbonic anhydrases are highly similar with regard to their structures, selective inhibition of different isoforms has been a significant challenge. By applying a proteochemometrics approach, herein the chemical interaction space governed by acyl selenoureido benzensulfonamides and human carbonic anhydrases is explored. To assess the validity, robustness and predictivity power of the proteochemometrics model, a diverse set of validation methods was used. The final model is shown to provide valuable structural information that can be considered for new selective inhibitors design. Using the supplied information and to show the applicability of the constructed model, new compounds were designed. Monitoring of selectivity ratios of new designs shows very promising results with regard to their selectivity for a specific isoform of carbonic anhydrase.

The Glitazone Class of Drugs as Carbonic Anhydrase Inhibitors-A Spin-Off Discovery from Fragment Screening.

The approved drugs that target carbonic anhydrases (CA, EC 4.2.1.1), a family of zinc metalloenzymes, comprise almost exclusively of primary sulfonamides (R-SO2NH2) as the zinc binding chemotype. New clinical applications for CA inhibitors, particularly for hard-to-treat cancers, has driven a growing interest in the development of novel CA inhibitors. We recently discovered that the thiazolidinedione heterocycle, where the ring nitrogen carries no substituent, is a new zinc binding group and an alternate CA inhibitor chemotype. This heterocycle is curiously also a substructure of the glitazone class of drugs used in the treatment options for type 2 diabetes. Herein, we investigate and characterise three glitazone drugs (troglitazone 11, rosiglitazone 12 and pioglitazone 13) for binding to CA using native mass spectrometry, protein X-ray crystallography and hydrogen-deuterium exchange (HDX) mass spectrometry, followed by CA enzyme inhibition studies. The glitazone drugs all displayed appreciable binding to and inhibition of CA isozymes. Given that thiazolidinediones are not credited as a zinc binding group nor known as CA inhibitors, our findings indicate that CA may be an off-target of these compounds when used clinically. Furthermore, thiazolidinediones may represent a new opportunity for the development of novel CA inhibitors as future drugs.

Is carbonic anhydrase inhibition useful as a complementary therapy of Covid-19 infection?

The ongoing Covid-19 is a contagious disease, and it is characterised by different symptoms such as fever, cough, and shortness of breath. Rising concerns about Covid-19 have severely affected the healthcare system in all countries as the Covid-19 outbreak has developed at a rapid rate all around the globe. Intriguing, a clinically used drug, acetazolamide (a specific inhibitor of carbonic anhydrase, CA, EC 4.2.1.1), is used to treat high-altitude pulmonary oedema (HAPE), showing a high degree of clinical similarities with the pulmonary disease caused by Covid-19. In this context, this preliminary study aims to provide insights into some factors affecting the Covid-19 patients, such as hypoxaemia, hypoxia as well as the blood CA activity. We hypothesise that patients with Covid-19 problems could show a dysregulated acid-base status influenced by CA activity. These preliminary results suggest that the use of CA inhibitors as a pharmacological treatment for Covid-19 may be beneficial.