probable interaction
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The world is under siege from a global pandemic caused by a novel class of coronaviruses called severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). These viruses cause severe respiratory illness leading to death. Molecular studies reveal that SARS CoV-2 proteases are involved in the processing of viral polyproteins. This study was conducted to obtain antiviral agents for SARS CoV-2 proteases. An extensive library of antiviral medicinal compounds was scrutinized to determine the probable interaction with both main and 3-chymotrypsin like proteases. Six antiviral compounds (Abietic Acid, Gallic Acid, Piceatannol, Piperine, Sinomenine, and Triptolide) were capable of establishing hydrogen bonds with the active pocket residues of the viral proteases, with appreciable binding energy. These compounds were subjected to root mean square analysis and tested not only for acute toxicity, but also for absorption, distribution, metabolism, excretion, and toxicity properties. Results were favourable for use in the treatment of SARS COV-2 infection.

Introduction: Adjuvant medications can be used to increase the analgesic effect of opioid analgesics, reduce the manifestation of side effects, and also for premedication. This paper provides information on the effect of clonidine, haloperidol, metocloparmide, diazepam, midazolam on opioid analgesics: - morphine and the selective kappa-opioid agonist compound RU-1205. Materials and methods: A probable interaction between RU-1205, morphine and adjuvant drugs in pain behaviors was carried out on the model of somatogenic pain. 95 male mice received either RU-1205 (5 mg/kg, i.p.) and morphine (1 mg/kg, i.p.) separately or in combination with haloperidol (0.45 mg/kg, i.p.); midazolam (0.3 mg/kg, i.p.); diazepam (1 mg/kg, i.p.); metoclopramide (5 mg/kg, i.p.), and clonidine (1 mg/kg, i.p.). The analgesic effect was assessed by tail flick test. Registration of the latent period of the reaction was carried out 30, 60 and 90 minutes after the adjuvant drug administration. Results: When studying the interaction with morphine, it was found that clonidine, haloperidol and metoclopramide enhanced the effects; diazepam offset them, and midazolam had no affect on the analgesic properties. In the course of the studies, RU-1205 showed an increase in analgesic activity when combined with clonidine, a slight increase with midazolam, and a decrease when co-administered with diazepam. Haloperidol had no influence on the effect of RU-1205, while metoclopramide both potentiated and reduced the analgesic effect. Discussion: Pharmacodynamic and pharmacokinetic interactions of RU-1205 with an α2AR agonist, benzodiazepine receptor agonists, D2P antagonist, and σ-receptor blocker were established. Conclusion: The presented data make it possible to more accurately formulate ideas about the localization and action mechanism of the kappa-agonist of opioid receptors, the compound RU-1205.

Purpose: To describe a potential drug interaction between warfarin and the combination of remdesivir with dexamethasone. Summary: Two male patients, a 71-year-old and 62-year-old presented to the emergency department for symptoms of coronavirus disease 2019 (COVID-19). Both patients were on long-term warfarin therapy with their most recent international normalized ratio (INR) prior to admission within their patient specific goal as managed by their outpatient Pharmacist. In both instances, the patients denied any changes in diet, lifestyle, or missed doses of medications upon admission interview. During admission, both patients experienced a marked elevation in INR within 24 to 48 hours of the initiation of remdesivir with dexamethasone for COVID-19 pneumonia directed therapy. The patients were both eventually stable and were instructed to continue warfarin monitoring and management under the direction of their outpatient Pharmacist upon discharge. Conclusion: The underrecognized but probable interaction between warfarin in conjunction with remdesivir and dexamethasone warrants further analysis.

Abstract We report a case of a man with COVID-19 who developed acute hepatotoxicity related to remdesivir with probable interaction of P-glycoprotein (P-gp) inhibitors. Until further details on this interaction become available, we recommend physicians to be cautious with the prescription of P-gp inhibitors in patients receiving remdesivir therapy.

Objective: To report a probable interaction between warfarin and edible cannabis that resulted in an elevated international normalized ratio (INR) without bleeding complications. Case Summary: A 35-year-old Middle Eastern male on warfarin long term with an INR goal of 2.5 (accepted range: 2.0-3.0). The patient has generally been stable on warfarin 10 mg daily from 2010 to 2018, until INR suddenly increased to 7.2 following 1 month of edible cannabis ingestion and cannabis smoking. Patient denied any signs and symptoms of bleeding. No other reasonable causes of the elevation in INR were apparent. The patient was advised to hold 2 doses of warfarin and discontinue cannabis use. The INR dropped below 4 upon discontinuation of cannabis with dose adjustments to warfarin. Discussion: The elevation in INR can be explained by the inhibition of CYP2C9 by cannabis use causing decreased metabolism of warfarin. The interaction between warfarin and cannabis was determined to be probable using the Horn Drug Interaction Probability Scale. Conclusions: There are no previous reports of interactions between edible cannabis and warfarin, with very few case reports describing the interaction with other forms of cannabis. Close monitoring of INR in patients with concomitant cannabis is recommended for proper warfarin management.

Te increase in the prevalence of arterial hypertension (AH) in populations, ineffective treatment, the need for risk stratifcation, prevention, early diagnosis and successful treatment, actualize genomic studies to develop a personalized therapeutic approach to AH. Te review investigates the possible genetically determined mechanisms of the development of hypertension and endothelial dysfunction caused by polymorphism of the genes of endothelial nitric oxide synthase (eNOS) and enzymes of phases I and II of the xenobiotics detoxifcation system. Te probable interaction of both systems under the influence of harmful environmental factors, including tobacco smoking, and in the gestational period is discussed. It is proposed to study AH candidate genes in the xenobiotics detoxifcation system, the carriage of different variants of which can determine the sensitivity or resistance to antihypertensive pharmacotherapy, which can be useful for developing of the personalized tactics of managing patients with AH.

ABSTRACTThe phosphoenolpyruvate-dependent phosphotransferase system (PTS) is the main carbohydrate uptake system inBacillus subtilis. A typical PTS consists of two general proteins, enzyme I (EI) and a histidine-containing protein (HPr), as well as a specific carbohydrate transporter (or enzyme II [EII]), all of which transfer the phosphoryl group from phosphoenolpyruvate to the transported carbohydrate. The specific PTS transporters are formed by multidomain proteins or single-domain subunits. These domains are domain C (EIIC), the transmembrane channel for the carbohydrate transport; domain B (EIIB), the membrane-bound domain responsible for phosphorylation of the carbohydrate; and domain A (EIIA), the mediator between HPr(H15∼P) and EIIB. There are 16 PTS transporters inB. subtilis, 6 of which, i.e., NagP, MalP, MurP, TreP, SacP, and SacX, contain no EIIA domain. Deletion of the single-EIIA-containing transporters showed that there is cross talk between the noncognate EIIA and EIIB domains in PTS. By deletion of all EIIA-containing proteins, strain KM455 (ΔEIIA) was constructed, and the EIIA-containing proteins were individually introduced into the strain. In this way, the PTS transporters of the glucose family, namely, PtsG, GamP, and PtsA (also known as YpqE), enabled growth with maltose,N-acetylglucosamine, sucrose, or trehalose as the sole carbon source. Construction of TkmA-EIIA fusion proteins confirmed the probable interaction between the EIIAs of the glucose family of PTS transporters and the EIIA-deficient PTS transporters. Likewise, we have shown that SacX is mainly phosphorylated by PtsA and GamP. PtsG and GmuA were also able to phosphorylate SacX, albeit less well than GamP and PtsA.IMPORTANCEThe phosphoenolpyruvate-dependent phosphotransferase system (PTS) not only is a carbohydrate uptake system inB. subtilisbut also plays an important role in sensing the nutrient fluctuation in the medium. This sensing system enables the cells to respond to these fluctuations properly. The PTS transporters have a pivotal role in this sensing system since they are carbohydrate specific. In this study, we tried to understand the interactions among these transporters which revealed the cross talk among PTSs. Three PTS proteins, namely, PtsG (the specific transporter of glucose), GamP (the specific transporter of glucosamine), and PtsA (a cytoplasmic single-domain EIIA protein) were shown to play the major role in the interaction among the PTSs.

Fullerenes and piperazines have been investigated, particularly, in the field of nanoscience and medicinal chemistry. In the present research, besides discussing structural and electronic properties, the most probable interaction mechanisms between C20, B-, Si-, Al-, Ga-doped C20 and 1,4-diformylpiperazine (1,4-dfp) were studied by employing density functional theory (DFT) in both the gas phase and water as the solvent. Stabilities of the investigated complexes were discussed based on the binding energy and electronic properties such as band gap energy, chemical hardness and electrophilicity index. It is found that doped complexes are more stabilized in water compared to the gas phase. However, the interaction between C20 and 1,4-dfp weakens upon the introduction of water as the solvent.