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Biomolecules ; 11(12)2021 12 18.
Article in English | MEDLINE | ID: covidwho-1581038


Hydrogen sulfide (H2S) is a ubiquitous gaseous signaling molecule that has an important role in many physiological and pathological processes in mammalian tissues, with the same importance as two others endogenous gasotransmitters such as NO (nitric oxide) and CO (carbon monoxide). Endogenous H2S is involved in a broad gamut of processes in mammalian tissues including inflammation, vascular tone, hypertension, gastric mucosal integrity, neuromodulation, and defense mechanisms against viral infections as well as SARS-CoV-2 infection. These results suggest that the modulation of H2S levels has a potential therapeutic value. Consequently, synthetic H2S-releasing agents represent not only important research tools, but also potent therapeutic agents. This review has been designed in order to summarize the currently available H2S donors; furthermore, herein we discuss their preparation, the H2S-releasing mechanisms, and their -biological applications.

Drug Discovery , Gasotransmitters/pharmacology , Hydrogen Sulfide/pharmacology , Animals , Benzenesulfonates/administration & dosage , Benzenesulfonates/metabolism , Benzenesulfonates/pharmacology , Benzenesulfonates/therapeutic use , Chemistry, Pharmaceutical , Gasotransmitters/administration & dosage , Gasotransmitters/metabolism , Gasotransmitters/therapeutic use , Humans , Hydrogen Sulfide/administration & dosage , Hydrogen Sulfide/metabolism , Hydrogen Sulfide/therapeutic use , Morpholines/administration & dosage , Morpholines/metabolism , Morpholines/pharmacology , Morpholines/therapeutic use , Naproxen/administration & dosage , Naproxen/analogs & derivatives , Naproxen/metabolism , Naproxen/pharmacology , Naproxen/therapeutic use , Organothiophosphorus Compounds/administration & dosage , Organothiophosphorus Compounds/metabolism , Organothiophosphorus Compounds/pharmacology , Organothiophosphorus Compounds/therapeutic use
Eur J Pharm Sci ; 157: 105631, 2021 Feb 01.
Article in English | MEDLINE | ID: covidwho-893750


BACKGROUND: Effective antiviral drugs for COVID-19 are still lacking. This study aims to evaluate the clinical outcomes and plasma concentrations of baloxavir acid and favipiravir in COVID-19 patients. METHODS: Favipiravir and baloxavir acid were evaluated for their antiviral activity against SARS-CoV-2 in vitro before the trial initiation. We conducted an exploratory trial with 3 arms involving hospitalized adult patients with COVID-19. Patients were randomized assigned in a 1:1:1 ratio into baloxavir marboxil group, favipiravir group, and control group. The primary outcome was the percentage of subjects with viral negative by Day 14 and the time from randomization to clinical improvement. Virus load reduction, blood drug concentration and clinical presentation were also observed. The trial was registered with Chinese Clinical Trial Registry (ChiCTR 2000029544). RESULTS: Baloxavir acid showed antiviral activity in vitro with the half-maximal effective concentration (EC50) of 5.48 µM comparable to arbidol and lopinavir, but favipiravir didn't demonstrate significant antiviral activity up to 100 µM. Thirty patients were enrolled. The percentage of patients who turned viral negative after 14-day treatment was 70%, 77%, and 100% in the baloxavir marboxil, favipiravir, and control group respectively, with the medians of time from randomization to clinical improvement was 14, 14 and 15 days, respectively. One reason for the lack of virological effect and clinical benefits may be due to insufficient concentrations of these drugs relative to their antiviral activities. One of the limitations of this study is the time from symptom onset to randomization, especially in the baloxavir marboxil and control groups, which is higher than the favipiravir group. CONCLUSIONS: Our findings could not prove a benefit of addition of either baloxavir marboxil or favipiravir under the trial dosages to the existing standard treatment.

Amides , COVID-19 , Dibenzothiepins , Morpholines , Pyrazines , Pyridones , Triazines , Amides/administration & dosage , Amides/blood , Amides/pharmacokinetics , Antiviral Agents/administration & dosage , Antiviral Agents/blood , Antiviral Agents/pharmacokinetics , COVID-19/blood , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/physiopathology , Dibenzothiepins/administration & dosage , Dibenzothiepins/blood , Dibenzothiepins/pharmacokinetics , Drug Monitoring/methods , Female , Humans , Inhibitory Concentration 50 , Male , Middle Aged , Morpholines/administration & dosage , Morpholines/blood , Morpholines/pharmacokinetics , Pyrazines/administration & dosage , Pyrazines/blood , Pyrazines/pharmacokinetics , Pyridones/administration & dosage , Pyridones/blood , Pyridones/pharmacokinetics , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Symptom Assessment , Treatment Outcome , Triazines/administration & dosage , Triazines/blood , Triazines/pharmacokinetics , Viral Load/drug effects