Bio-Chemoinformatics-Driven Analysis of nsp7 and nsp8 Mutations and Their Effects on Viral Replication Protein Complex Stability DOI Creative Commons
Bryan John J. Subong,

Takeaki Ozawa

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(3), P. 2598 - 2619

Published: March 18, 2024

The nonstructural proteins 7 and 8 (nsp7 nsp8) of SARS-CoV-2 are highly important involved in the RNA-dependent polymerase (RdRp) protein replication complex. In this study, we analyzed global mutation nsp7 nsp8 2022 2023 effects on viral complex using bio-chemoinformatics. Frequently occurring variants found to be single amino acid mutations for both nsp8. most frequently which include L56F, L71F, S25L, M3I, D77N, V33I T83I predicted cause destabilizing effects, whereas those stabilizing with threonine isoleucine (T89I, T145I, T123I, T148I, T187I) being a frequent mutation. A conserved domain database analysis generated critical interaction residues (Lys-7, His-36 Asn-37) (Lys-58, Pro-183 Arg-190), which, according thermodynamic calculations, prone destabilization. Trp-29, Phe-49 Trp-154, Tyr-135 Phe-15 greater based computational alanine scan suggesting them as possible new target sites. This study provides an intensive their implications stability.

Language: Английский

Chemical metabolite synthesis and profiling: Mimicking in vivo biotransformation reactions DOI
Amol Chhatrapati Bisen, Sachin Nashik Sanap, Sristi Agrawal

et al.

Bioorganic Chemistry, Journal Year: 2023, Volume and Issue: 139, P. 106722 - 106722

Published: July 8, 2023

Language: Английский

Citations

18

Etiopathology, Epidemiology, Diagnosis, and Treatment of Fungal Keratitis DOI
Amol Chhatrapati Bisen, Sachin Nashik Sanap, Sristi Agrawal

et al.

ACS Infectious Diseases, Journal Year: 2024, Volume and Issue: 10(7), P. 2356 - 2380

Published: June 7, 2024

Fungal keratitis (FK) is a severe ocular condition resulting from corneal infection that prevalent in tropical countries, particularly developing regions of Asia and Africa. Factors like lens misuse, inappropriate steroid use, diagnostic challenges have provoked the epidemic. FK causes significant vision impairment, scarring, deformities. Accurate pathological diagnosis crucial for effective therapeutic intervention. Topical antifungal therapy with surface healing medications proves preventing fungal-borne ulcers. Managing requires comprehensive understanding fungal pathogenesis, guiding formulation strategies preventive measures to curb global blindness. This review provides in-depth insights into FK, covering etiology, epidemiology, interventions, resistance, limitations, prevention, future perspectives on disease management.

Language: Английский

Citations

9

Ocular Bioanalysis of Moxifloxacin and Ketorolac Tromethamine in Rabbit Lacrimal Matrix Using Liquid Chromatography–Tandem Mass Spectrometry DOI
Amol Chhatrapati Bisen, Rabi Sankar Bhatta

Bioanalysis, Journal Year: 2024, Volume and Issue: 16(4), P. 219 - 232

Published: Jan. 10, 2024

Aim: The fixed-dose combination of moxifloxacin (MOXI) and ketorolac tromethamine (KTR) is widely used for the treatment bacterial keratitis. Thus, a new LC–MS/MS method was developed to determine MOXI KTR in lacrimal fluid. Methods: Bioanalysis performed using Shimadzu 8050 electrospray ionization-positive mode validated per US FDA guidelines. Isocratic separation with Waters Symmetry C18 column methanol 0.1% formic acid containing deionized water (85:15, v/v). Results & conclusion: An easy, quick selective established applied assess ocular pharmacokinetic profile commercially available formulation KTR. Based on data, this work describes pharmacokinetics-based dosage regimen calculations their clinical significance.

Language: Английский

Citations

8

Codetermination of antimicrobial agents in rabbit tear fluid using LC–MS/MS assay: Insights into ocular pharmacokinetic study DOI
Amol Chhatrapati Bisen,

Anjali Mishra,

Sristi Agrawal

et al.

Journal of Mass Spectrometry, Journal Year: 2024, Volume and Issue: 59(6)

Published: May 10, 2024

Abstract Managing ocular microbial infections typically requires pharmacotherapy using antibiotic eye drops, such as moxifloxacin hydrochloride (MFX), combined with an antifungal agent like amphotericin B (AB). We carried out and validated LC–MS/MS assay to quantify these compounds in rabbit tear fluid order look into the pharmacokinetics of two drugs. employed a protein precipitation technique for extraction drugs under examination. A Waters Symmetry C 18 column was used separate analytes internal standard. The composition mobile phase (A) 0.1% v/v formic acid water (B) methanol. detection MFX AB accomplished through utilization positive ion electrospray ionization multiple reaction monitoring mode. linearity curves both exhibited acceptable trendline across concentration range 2.34–300 ng/mL 7.81–1000 surrogate fluid. lower limit quantitation 2.34 ng/mL, while AB, it 7.81 ng/mL. approach strictly validated, encompassing tests selectivity, (with r 2 > 0.99), precision, accuracy, matrix effects, stability. Consequently, we this method evaluate profiles following single topical doses.

Language: Английский

Citations

5

Recent updates on ocular disease management with ophthalmic ointments DOI
Amol Chhatrapati Bisen, Ayush Dubey, Sristi Agrawal

et al.

Therapeutic Delivery, Journal Year: 2024, Volume and Issue: 15(6), P. 463 - 480

Published: June 2, 2024

Ophthalmic diseases can result in permanent vision loss and blindness. Convenient topical systemic treatments are preferred to address these sight-threatening conditions. However, the unique anatomy of eye presents challenges for drug delivery. Various ophthalmic ointment formulations have been developed enhance bioavailability prolong residence time improve corneal permeability. This article explores a wide range ocular affecting individuals globally how ointments used manage them. From barriers, this review focuses on published scientific research formulation strategies severe complications using conventional ointments. Additionally, it delves through patented technologies marketed supporting use

Language: Английский

Citations

4

Impact of the COVID-19 Pandemic on Gut Cancer Admissions and Management: A Comparative Study of Two Pandemic Years to a Similar Pre-Pandemic Period DOI Open Access
Sergiu Marian Cazacu, Ion Rogoveanu, Adina Turcu-Ştiolică

et al.

Healthcare, Journal Year: 2025, Volume and Issue: 13(7), P. 805 - 805

Published: April 3, 2025

Background/Objective: Gastrointestinal tract cancers may have been severely affected by the COVID-19 pandemic. The limitations of digestive endoscopy, fear effect, and restrictions on hospital admissions during pandemic delayed presentation patients to hospitals surgical procedures impacted overall survival. Methods: We conducted an observational, cross-sectional study esophageal, gastric, small bowel, colorectal cancer admitted our between 1 January 2018 31 December 2021. analyzed hospitalization rates, pathological type, onset complications, staging, surgery compared a pre-pandemic period (January 2018-December 2019). Results: During 2018-2021, 1613 with malignant gut tumors were (112 esophageal eso-cardial tumors, 419 gastric 34 bowel 1058 tumors). Admission was reduced 30.3% for 27.6% 17.3% tumors. For higher frequency stenosing palliative gastrostomies noted. More stage III lower rate vascular invasion recorded No differences regarding In slightly more II recorded, but occlusive, bleeding, perforated similar; also, rates similar, two-fold perioperative mortality. survival carcinoma (but no statistical significance), although clear explanation has not emerged. Conclusions: impact included significantly newly diagnosed admissions, carcinomas, mortality carcinoma, trend surprisingly without significance). Future research is necessary assessing long-term impact.

Language: Английский

Citations

0

Hesperidin: Enrichment, forced degradation, and structural elucidation of potential degradation products using spectral techniques DOI Open Access
Amol Chhatrapati Bisen, Priyanka Rawat, G. C. Sharma

et al.

Rapid Communications in Mass Spectrometry, Journal Year: 2023, Volume and Issue: 37(20)

Published: Aug. 31, 2023

Hesperidin (HES) is a well-known citrus bioflavonoid phyto-nutraceutical agent with polypharmacological properties. After 2019, HES was widely used for prophylaxis and COVID-19 treatment. Moreover, it commonly prescribed treating varicose veins other diseases in routine clinical practice. Pharmaceutical impurities degradation products (DP) impact the drug's quality safety thus its effectiveness. Therefore, forced studies help study drug stability, mechanisms, their DPs. This performed because stress stability using detailed structural characterization of hesperidin are currently unavailable literature.In enrichment method crude converted to pure form (98% purity) column chromatography then subjected under acid, base, neutral hydrolyses followed by oxidative, reductive, photolytic, thermal testing (International Conference on Harmonization guidelines). The stability-indicating analytical (SIAM) developed determine DPs reversed-phase high-performance liquid (C18 methanol 0.1% v/v acetic acid deionized water [70:30, v/v] at 284 nm). Further, chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) nuclear magnetic resonance (NMR) spectroscopy. In addition, silico toxicity predictions were pKCSM DataWarior freeware.HES found be susceptible acidic basic hydrolytic conditions yielded three each, which detected designed SIAM. Of six DPs, pseudo-DPs (short lived), remaining characterized LC-MS/MS NMR tentative mechanism formation proposed explained. inactive from predictions.Hesperidin labile conditions. potential LC-ESI-MS/MS spectral techniques. hypothesized. identify characterize SIAM, has broad biomedical applications, successfully developed.

Language: Английский

Citations

6

Bio-Chemoinformatics-Driven Analysis of nsp7 and nsp8 Mutations and Their Effects on Viral Replication Protein Complex Stability DOI Creative Commons
Bryan John J. Subong,

Takeaki Ozawa

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(3), P. 2598 - 2619

Published: March 18, 2024

The nonstructural proteins 7 and 8 (nsp7 nsp8) of SARS-CoV-2 are highly important involved in the RNA-dependent polymerase (RdRp) protein replication complex. In this study, we analyzed global mutation nsp7 nsp8 2022 2023 effects on viral complex using bio-chemoinformatics. Frequently occurring variants found to be single amino acid mutations for both nsp8. most frequently which include L56F, L71F, S25L, M3I, D77N, V33I T83I predicted cause destabilizing effects, whereas those stabilizing with threonine isoleucine (T89I, T145I, T123I, T148I, T187I) being a frequent mutation. A conserved domain database analysis generated critical interaction residues (Lys-7, His-36 Asn-37) (Lys-58, Pro-183 Arg-190), which, according thermodynamic calculations, prone destabilization. Trp-29, Phe-49 Trp-154, Tyr-135 Phe-15 greater based computational alanine scan suggesting them as possible new target sites. This study provides an intensive their implications stability.

Language: Английский

Citations

1